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W2807209546 abstract "The American Society of Colon and Rectal Surgeons is dedicated to ensuring high-quality patient care by advancing the science, prevention, and management of disorders and diseases of the colon, rectum, and anus. The Clinical Practice Guidelines Committee is composed of society members who are chosen because they have demonstrated expertise in the specialty of colon and rectal surgery. This committee was created to lead international efforts in defining quality care for conditions related to the colon, rectum, and anus. This is accompanied by developing clinical practice guidelines based on the best available evidence. These guidelines are inclusive and not prescriptive. The purpose of this guideline is to provide information on which decisions can be made rather than to dictate a specific form of treatment. These guidelines are intended for use by all practitioners and healthcare workers, as well as by patients who desire information about the management of the conditions addressed by the topics covered in these guidelines. It should be recognized that these guidelines should not be deemed inclusive of all proper methods of care or exclusive of methods of care reasonably directed toward obtaining the same results. The ultimate judgment regarding the appropriateness of any specific management decision must be made by the treating physician in light of all of the circumstances present in the care of the patient in question. STATEMENT OF THE PROBLEM Squamous cell cancers of the anal canal and perianal region remain one of the least common malignancies arising from the alimentary tract. As of 2016, it is estimated that 8200 new cases of squamous cell cancers of the anus were diagnosed in the United States, with 1.7 times as many women as men affected.1 Within this same time period, ≈1100 patients were estimated to have died of anal cancer, with cancer deaths among women being 1.4 times the number observed among men. Although squamous cancers of the anus remain relatively rare GI malignancies, 2 factors have nonetheless focused greater attention toward this disease. The first is the observation that the frequency of squamous cancers of the anus has increased in the United States from the 1970s through the 2000s,2 with a notable increase in incidence among men, and, in particular, black men.3 In addition, given the inverse relationship between stage of disease and survival,4 studies using population-level data suggest that earlier detection may improve survival from anal cancer, which makes anal cancer an important and treatable public health concern. The second factor that has resulted in a paradigm shift in understanding the etiology of anal cancer is the discovery that the human papilloma virus (HPV), especially HPV serotypes 16 and 18,5 is the primary cause of squamous cancers of the anus,6,7 making anal cancer a sequela of a sexually transmitted disease. This aspect of anal carcinogenesis reinforces the concept that it is a potentially preventable disease and that if evidence-based screening and preventative measures were developed and consistently applied, decreases in cancer-related deaths would follow. The modifiable risk of death from anal cancer is further underscored by large studies that have documented that ≈50% of patients with anal cancer present with localized, node-negative disease, which is associated with high cure rates; one third of patients will present with node-positive disease, whereas only 10% to 15% will present with distant metastases.8 Thus, even without effective preventative measures, the majority of patients with anal cancer are potentially curable at the time of diagnosis and treatment. The multiple risk factors associated with developing squamous cancers of the anus are well documented and can be grouped into the 2 broad categories of HPV and immunosuppression, although there is also an association between these categories as well. Among the HPV-related risk factors include lifetime number of sexual partners,9 a history of previous sexually transmitted diseases of any kind,10 a history of anogenital warts,11 anoreceptive intercourse,12 and a history of cervical, vaginal, or vulvar cancer.13 Risk factors related to immunity include a diagnosis of HIV,14 autoimmune disorders such as lupus and sarcoidosis,15 and being the recipient of a solid organ transplant.16 Female sex3 and cigarette smoking17 are also associated with developing anal malignancies. ANATOMIC CONSIDERATIONS AND TERMINOLOGY The management of anal cancers requires a multidisciplinary approach, and the unfamiliarity of nonsurgical disciplines with anorectal anatomy can create ambiguity in describing the location and the clinical stage of anal cancers across disciplines. The anal canal, as viewed by colorectal surgeons, is ≈4 to 5 cm in length beginning at the distal rectum, where the mucosa blends into the anal transitional zone (ATZ) epithelium, which then transitions to nonkeratinized squamous epithelium as it further transitions into keratinized perianal skin at the anal verge. An ATZ, located several millimeters proximal to the dentate line and extending for 0.5 to 1.5 cm in length, represents a region of naturally occurring intestinal metaplasia, representing a transition from the columnar epithelium of the distal rectum to the modified squamous epithelium of the anal canal, referred to as anoderm. Because of the presence of metaplasia in the ATZ, this region is particularly susceptible to HPV infection.18 In addition, the variety of tissue types in the ATZ have been associated with a number of subtypes of squamous cancers of the anus of both keratinizing and nonkeratinizing histologies. Although there were previous efforts to distinguish between histological subtypes of anal cancer, all of these subtypes are now grouped together, because multiple histological variants can exist within the same malignancy,19 and because the natural history and survival of these subtypes are similar when stratified by treatment and cancer stage.20 Because the anatomic landmarks of the anus will not be easily identifiable by nonsurgical providers who are also untrained in techniques such as anoscopy and proctoscopy, a simplified taxonomy21 has been suggested. An anal canal cancer would be any lesion that cannot be completely visualized with distraction of the gluteal cheeks, whereas a perianal (which replaces the term anal margin) lesion can be completely visualized with distraction of the gluteal cheeks, and that is still within 5 cm of the anal orifice. Any lesion >5 cm from the anal orifice would be classified as a skin lesion and would not be considered related to the GI tract. Confusion often arises over the various pathology terms commonly used to describe lesions involving the anus and perianal skin. The Lower Anogenital Squamous Terminology project unified terminology for all HPV-related squamous precursor lesions with a 2-tiered nomenclature system.22,23 This system simply designates noninvasive pathology as either low-grade or high-grade squamous intraepithelial lesions (LSILs and HSILs) based on histological findings such as mitotic activity, depth of dermal involvement, and abnormalities in squamous cell differentiation. LSILs include anal intraepithelial neoplasia (AIN) 1, whereas HSILs encompass AIN-2 and AIN-3 designations. The distinction between condylomas and LSILs is somewhat arbitrary; condylomas generally appear as bland exophytic, papillary proliferations with viral cytopathic changes, whereas LSILs tend to be flat lesions.23 Older terms such as Bowen’s disease should no longer be used. Throughout this Clinical Practice Guideline, the terms LSIL and HSIL will be used, although reference to AIN may appear when directly quoting published research findings. This guideline only discusses the management of premalignant and malignant squamous neoplasms of the anus and perianal region, excluding other, rarer malignancies. The abbreviation SCC will be used to refer to squamous cell cancers. METHODS These guidelines were built on the most recent American Society of Colon and Rectal Surgeons Practice Parameters for Anal Squamous Neoplasms, published in 2012.24 An organized search of MEDLINE, PubMed, Embase, and the Cochrane Database of Collected Reviews was queried June 2015 through January 2018, searching for relevant publications with no limitations regarding date of publication. Retrieved publications were limited to the English language, but no limits on year of publication were applied. The search strategies were based on the key words anal cancer and anal squamous cancer as primary search terms, with additional, key-word searches including AIN, anal intraepithelial neoplasia, Nigro protocol, anal HPV, LSIL, and HSIL. Searches were also performed based on various treatments for anal cancers, including “anal cancer AND radiation,” “anal cancer AND chemoradiotherapy,” “anal cancer AND surgery,” “anal cancer AND abdominoperineal resection,” “anal cancer AND anal dysplasia,” and “anal cancer and lymphadenectomy.” Directed searches of the embedded references from the primary articles were also performed in certain circumstances. Prospective randomized controlled trials (RCTs) and meta-analyses were given preference in developing these guidelines. The final grade of recommendation was performed using the Grades of Recommendation, Assessment, Development, and Evaluation system (Table 1).25TABLE 1.: Grade scoring systemPremalignant Neoplasms of the Anal Canal and Perianal Region Patients at increased risk for anal squamous neoplasms should be identified by history, physical examination, and laboratory testing, noting that the risk is higher in HIV-positive individuals, men who have sex with men (MSM), and women with a history of cervical dysplasia. Grade of Recommendation: Strong recommendation based on moderate-quality evidence, 1B. Multiple large (300- to 1200-patient) cohort studies have identified risk factors for anal dysplasia and cancer.26,27 A systematic review and meta-analysis noted that the pooled prevalence of HPV-16 in HIV-positive MSM was 35.4%.28 The prevalence of AIN was 29.1%, and the incidence of anal cancer was 45.9 per 100,000 men. For HIV-negative MSM, the prevalence of HPV-16 was 11.8%, the prevalence of AIN was 21.5%, and the incidence of anal cancer was 5.1 per 100,000 men. A cohort of 171 HIV-positive women noted that 12.9% had HSILs.29 Cervical dysplasia can also guide risk assessment in women; a population-based study of 89,018 women with cervical HSILs matched with control subjects without cervical dysplasia demonstrated an increased rate of anal cancer (relative risk = 6.68 (95% CI, 3.64–12.25)) and HSILs (relative risk = 4.97 (95% CI, 3.26–7.57)).30 Standardized nomenclature with a 2-tiered system should be used. Biomarkers, including p16, should be used selectively to clarify equivocal high-grade lesions. Grade of Recommendation: Strong recommendation based on low- or very-low–quality evidence, 1C. There are advantages in standardizing terminology in defining the disease and treatments. The 2-tiered system22,23 defined in 2012 provides the most appropriate system for standardizing definitions. Two retrospective studies have shown that there can be inconsistent interrater reliability when examining histology specimens.31 Evidence supporting this 2-tiered system is based in part on 1 prospective blinded study that reported that interrater reliability for cytology using a 2-tiered system was 85% and that p16 staining and HPV oncogene messenger RNA analysis improved the ability to come to a diagnostic consensus.32 Individuals with anal dysplasia should be followed at regular intervals with a history, physical examination, and a discussion of screening options. Grade of Recommendation: Weak recommendation based on moderate-quality evidence, 2B. Prevention of cervical cancer with screening for precancerous lesions has been proven effective.31 Whether a similar program of screening and destruction of precancerous anal lesions will lead to reductions in anal cancer is a matter of considerable debate. A 2012 systematic review and meta-analysis suggested that, as part of their natural history, rates of progression to anal cancer are substantially lower than those observed for cervical cancer.28 Regardless of which, if any, intensive screening program is selected, individuals with anal dysplasia should have a periodic office visit to assess for any new or modifiable risk factors, including a digital anorectal examination. Even in an intensive screening program, nearly all the cancers that developed were detectable on digital examination.33 It is not clear that screening will prevent a cancer from occurring, but there is evidence that cancers detected during a screening program are identified at an early stage.33 Multiple cohort studies have shown progression from low-grade to high-grade dysplasia and from dysplasia to cancer even under regimented surveillance. A cohort of 91 HIV-positive patients treated for anal dysplasia followed for >1 year showed that 75.8% had recurrent dysplasia, 46.0% progressed to high-grade dysplasia, and 2.3% developed anal cancer.34 Studies of 4 cohorts of patients in intensive treatment programs have separately estimated the development of cancer despite treatment, although all recorded the risk differently. One estimated the rate of progression to cancer at 6.9 cases per 100 person-years of follow up,35 another estimated the Kaplan–Meier probability of SCC at 3 years at 1.97%,36 a third estimated the duration to development of SCC at 57 to 62 months,33 and a fourth estimated the 5-year cumulative incidence of SCC at 1.70%.37 There is consensus among experts that an HSIL is the precursor to invasive cancer.33,38 What remains unclear is whether screening to identify and ablate premalignant lesions will decrease the incidence of SCC. Nevertheless, even if the progression to cancer cannot be halted, early diagnosis of a cancer justifies follow-up, and a history and examination to identify and treat visible and palpable lesions and/or a discussion of screening options is justified. Screening with anal cytology (or anal Papanicolaou (Pap) tests) may be considered in high-risk populations as part of a comprehensive screening program, but the sensitivity and specificity of the test do not support its use for universal screening. Grade of Recommendation: Weak recommendations based on moderate-quality evidence, 2B. Similar to cervical Pap smear cytology, a swab or brush sample from the anal canal to include the ATZ can be evaluated for cytological evidence of dysplasia. Although the data demonstrating effectiveness for cervical cancer screening and prevention are well founded, substantial efforts to prove its role in anal cancer screening have not been conclusive. Because screening tests perform better as the prevalence of a condition is higher, screening a higher-risk population will be more effective. Most studies screen high-risk individuals, including MSM, HIV-positive persons, and/or women with a history of cervical dysplasia. Results from studies that have performed both anal cytology and histologic evaluation are shown in Table 2.12,29,39–52 The sensitivity and specificity are limited, because the gold standard is the finding of HSILs on biopsies. Currently the ability of anal cytology to identify patients at risk for dysplasia is inconclusive, and an association between anal cytology and reduced rates of anal cancer has not been demonstrated. The decision to perform anal Pap tests should be a shared decision with the patient, including a discussion about how abnormal tests will be further evaluated.Table 2.: Studies of anal cytology and histologic evaluation for squamous intraepithelial lesionsHPV testing may be used as an adjunct to screening for anal cancer. Grade of Recommendation: Weak recommendations based on moderate-quality evidence, 2B. The presence of HPV, especially subtypes 16 and 18, is associated with the majority of anal cancers. Biomarkers screen for the presence of high-risk HPV to estimate the risk of dysplasia. The main limitation to this strategy is the high prevalence of HPV in the high-risk population. Currently available options include HPV DNA testing, HPV DNA genotyping for HPV-16 and HPV-18, HPV-E6/E7 mRNA testing, and p16/Ki-67 immunostaining based on either anal cytology or biopsy. P16 is a tumor suppressor gene product that indicates HPV integration into the host genome. The Lower Anogenital Squamous Terminology guidelines recommend the use of p16 in borderline HSIL/LSIL cases, with strong positive staining leading to an HSIL diagnosis and weak or absent staining supporting an LSIL diagnosis. The use of p16 staining, or any of the biomarkers, in a screening setting is less clear. Two prospective studies have compared anal cytology with HPV testing, as have multiple retrospective cohorts. The ANALOGY trial prospectively evaluated screening with cytology, high-risk HPV typing, and high-resolution anoscopy (HRA). With HPV testing only 59% of HSILs would have been detected.12 The Australian study used high-risk HPV viral load and high-risk HPV-E6/E7 mRNA, as well as cytology and HRA.39 Compared with cytology for the detection of HSIL, HPV testing showed similar sensitivity and improved specificity for the detection of HSILs, especially in the HIV-negative group. HRA may be considered as a screening option for patients at high risk for cancer when performed by clinicians with appropriate training in the procedure. Recommendation: Weak recommendation based on moderate-quality evidence, 2B. HRA is a procedure performed in the office or in the operating room using magnification and topical agents such as acetic acid and Lugol’s solution to identify, biopsy, and ablate lesions not visible by conventional examination or anoscopy. The procedure can be more cost-effective if performed in the office. In addition, because it is superior to cytology or HPV testing in identifying HSILs, HRA may be more cost-effective than other strategies; the cost per HSIL found has been estimated to be $809.39. A prospective screening study of high-risk MSM evaluated all 3 modalities of HPV testing, cytology, and HRA.12 In a cohort of 284 MSM, AIN-3 was detected in 17 patients, with screening HRA finding 16, HPV-16/18 testing finding 10, any HPV testing finding 16, high-grade cytology detecting 3, and any abnormal cytology detecting 12 subjects. However, only 15% of the cohort tested negative for HPV, representing a methodologic weakness in this study. Cytology missed nearly one third of high-risk lesions, suggesting that HRA would have the most clinical use for screening. The effectiveness of HRA to prevent the progression of dysplasia or development of cancer has been evaluated in retrospective cohort studies. A retrospective review of 246 patients treated with HRA-targeted destruction of HSIL/LSIL over a 10-year period was published in 2008.53 A recurrent HSIL was seen in 57% of patients at an average of 19 months. Despite treatment, 1.2% progressed to invasive cancer. A cohort of 727 MSM followed for a median of 2.2 years was published in 2014. With ablation of all HRA-identified lesions and with regular follow-up, the rate of recurrence at 1 year was 53% in HIV-positive patients and 49% in HIV-negative patients. Over the follow-up period, 5 patients developed cancer, with the probability of cancer 1.97% at 3 years.36 There are few comparisons of HRA with other treatment strategies. A retrospective review of 424 patients compared HRA with expectant management in 2 cohorts, one treated by 3 clinicians who followed patients with expectant management and the other treated by 2 clinicians who followed patients with HRA.54 Anal cancer occurred in 1 of the HRA patients and 2 of the expectant management patients. The 5-year progression rate was similar in the 2 cohorts. Selection bias and the possibility for type II error limit these findings. Performing HRA requires specialized training and ongoing practice to perform good-quality examinations.55,56 In addition, patient compliance, patient tolerance, and the risk of over treatment have led some clinicians to wait to start performing HRA until additional data are available. Although HRA effectively identifies HSIL, whether HRA with ablation of HSIL can reduce the incidence of cancer or whether it can do so more consistently than conventional anoscopy remains unclear. Topical imiquimod, fluorouracil, trichloroacetic acid and cidofovir with close long-term follow-up are each options for the treatment of LSIL or HSIL. Grade of Recommendation: Weak recommendation based on moderate-quality evidence, 2B. Two randomized trials and 1 prospective cohort study have evaluated imiquimod. A placebo-controlled RCT of 64 HIV-positive patients with HSILs who were followed with HRA suggested superior clearance of HSILs with imiquimod (42.9% vs 4.0%).57 With a median follow-up of 33 months, 61% showed a sustained absence of HSILs. An RCT comparing imiquimod with topical fluorouracil and electrocautery found that 24% of HSILs had resolved and 11% had a partial response with imiquimod.58 Although electrocautery had a statistically significant improvement in response when the p value was calculated for the 3 treatment options, the difference was not significant if imiquimod and electrocautery were compared head to head. A third prospective cohort study evaluated imiquimod 5 days per week and found that the overall response rate for HSILs was 66%.59 Two retrospective studies have evaluated topical fluorouracil. A retrospective review of 46 patients with HSILs or LSILs showed that 57% responded to topical fluorouracil, with 39% having a complete response.60 A second review of 11 patients with dysplasia (although only 5 had HSILs) showed a decrease in dysplasia in 6 (55%) of 11 patients.61 Two retrospective cohort studies have examined the use of trichloroacetic acid. A review of 98 HSILs from 72 patients demonstrated that 28.7% of lesions had resolution or downgrading to LSILs on follow-up, although recurrence occurred in 20.8% of the lesions.62 A review of 54 men showed that, on a per-lesion basis, 72% of HSILs cleared to LSIL or less.63 Cidofovir has been evaluated in 1 prospective pilot study and 1 retrospective cohort study. The pilot study included 16 HIV-positive patients with HSILs and revealed a complete response rate of 10 (62.5%) of 16, although 2 (20.0%) of 10 had recurrent HSILs at the 24-week end point of the study.64 A small cohort of 24 patients with HSILs demonstrated that 51% had responsive disease, with a complete response observed in 15% of patients.65 Ablative treatments with conventional anoscopy or HRA are appropriate therapies for HSILs. Grade of Recommendation: Weak recommendation based on moderate-quality evidence, 2B. If HRA is used as the primary screening modality, ablative therapies can be used as first-line treatment for dysplasia. A prospective cohort of 98 patients with HSILs treated with infrared coagulation (IRC) showed that 74% had no additional evidence of HSILs on short-term follow-up.66 There was a comparison to expectant management in that study, but the control group was derived from patients who delayed or declined treatment, and patients who missed follow-up were excluded. In light of these limitations, the findings in this study are best viewed as a cohort treated with IRC. Three reviews have been published from a single center, and it is unclear how much overlap exists.67–69 Findings from the most recent review, a retrospective review of 96 MSM with HSILs treated with ≥1 IRC showed that 82% of HIV-positive and 90% of HIV-negative individuals were free from HSILs, but recurrence rates were high in the study, and nearly one third of patients were lost to follow-up.69 A retrospective review of 78 HSILs in 68 HIV-positive MSM showed 64% efficacy per treated lesion.70 A retrospective review of 66 patients with HSILs treated with IRC reported that only 13% had recurrent HSILs at 1 year of follow-up.71 Electrocautery ablation was reviewed in a cohort of 232 MSM with HSIL.72 Initial clearance rates were high (75%–80%), but recurrences were common (53%–61%), and 1 patient in the cohort developed cancer despite treatment. A cohort of 83 patients treated for HSIL with electrocautery found a complete or partial response in 66.2%.73 With a mean follow-up of 12.1 months, 25.4% of patients had a high-grade recurrence. A single-center review of 3 ablative techniques, electrocautery, IRC, or laser treatments, showed no differences in the rate of recurrence.36 One prospective RCT compared imiquimod, topical fluorouracil, and electrocautery in HIV-positive MSM with confirmed AIN.58 Resolution of AIN was achieved in 24% of patients in the imiquimod group, 17% of the topical fluorouracil group, and 39% of the electrocautery group (p = 0.008 for electrocautery vs fluorouracil; p = 0.10 for electrocautery vs imiquimod). Vaccination against HPV in men and women under age 26 years for primary prevention is typically recommended. Vaccination of individuals with anal dysplasia for secondary prevention of dysplasia and cancer is not recommended. Grade of Recommendation: Weak recommendation based on high-quality evidence, 2A. The availability of bivalent, quadrivalent, and now nonavalent vaccines has created considerable promise that the next generation of individuals will be largely exempt from HPV-related neoplasms. Although there are convincing data for use of the vaccine in pre-exposure young individuals, the off-label use of the vaccine in those with anal dysplasia is of considerable interest. A systematic review and meta-analysis of the efficacy of the vaccine in cervical dysplasia showed that it had no effect.74 A systematic review including all of the sites reported that 9 of 12 studies performed in patients with active disease showed decreased disease recurrence, but no study reported improved outcomes without clinical disease.75 However, enthusiasm for the vaccine for secondary prevention or regression of dysplasia gained attention after a study of 602 MSM who were randomly assigned to receive either the quadrivalent HPV vaccine or placebo. Those who received the vaccine had a lower rate of intraepithelial neoplasia, and the rate of HSILs was reduced by 54%.5 A comparative cohort study of 202 patients with previous HSILs treated with or without the quadrivalent vaccine demonstrated that vaccine treatment was associated with decreased risk of recurrent HSILs.76 A prospective, randomized, National Institutes of Health–funded trial including 574 patients has been completed and presented in abstract form, and the results are available at clinicaltrials.gov (NCT01461096). The number of participants with biopsy-proven HSIL occurrences and recurrences at 1 year or abnormal cytology at 1, 2, or 3 years was the same. Patients who have been treated for anal dysplasia may be observed without regular cytology, HPV testing, or HRA; however, treatment of visible or palpable disease should be offered. Grade of Recommendation: Weak recommendation based on low or very low-quality evidence, 2C. Although it is generally accepted that HSIL is a precursor to invasive cancer, there remain no studies that compare more intensive screening and/or HRA protocols with office examinations, conventional anoscopy, and treatment of visible or palpable disease. A review of 574 patients in an HRA program showed that 24% of patients with HSIL had spontaneous regression to LSIL.77 The progression to cancer is often multifactorial, including contributions from medication compliance, immunosuppression, HIV viral load, ongoing exposure to HPV, smoking, and a variety of other factors. In the largest prospective randomized US trial, which is currently enrolling, the control arm of the study includes no treatment of HRA-identified HSILs. The Topical or Ablative Treatment in Preventing Anal Cancer in Patients With HIV and Anal High-Grade Squamous Intraepithelial Lesions trial (NCT02135419) will screen HIV-positive patients with HRA and targeted biopsies. Previously untreated individuals who have HSILs identified will be randomly assigned to treatment or monitoring. For patients who are treated, the clinician decides whether the patient should have topical treatment or ablative treatment. Patients with topical treatment may receive imiquimod, fluorouracil, or trichloroacetic acid. Patients with ablative treatment may have IRC, electrocautery, or laser ablation. In the study, number and frequency of the treatments is left to the discretion of the treating physician. For patients who are observed, examinations and cytology are performed every 6 months, with biopsies of any visible lesions. Therefore, although screening and preventative treatment remain controversial, expectant management with treatment of visible or palpable disease remains an option unless or until emerging evidence suggests that screening and ablation of subclinical lesions are beneficial to reduce the incidence of anal cancer. MALIGNANT NEOPLASMS OF THE ANAL CANAL AND PERIANAL REGION Pretreatment Evaluation A disease-specific history and physical examination should be performed, emphasizing symptoms, risk factors, and signs of advanced disease. Grade of Recommendation: Strong recommendation based on low-quality evidence, 1C. Most patients present with a slow-growing mass involving either the anal canal or the perianal skin.78 Pain and bleeding are common, occurring in approximately half of patients, although <20% of patients may be asymptomatic.10,79 Diagnosis of anal SCC may often be delayed, mainly because of nonspecific anorectal symptoms, which are frequently attributed to benign anorectal pathology, such as hemorrhoids, in <70% to 80% of patients.78,80 Patients with locally advanced anal cancers may also prese" @default.
W2807209546 created "2018-06-13" @default.
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W2807209546 date "2018-07-01" @default.
W2807209546 modified "2023-10-14" @default.
W2807209546 title "The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for Anal Squamous Cell Cancers (Revised 2018)" @default.
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