surgical considerations in anal cancer

Surg Oncol Clin N Am

13 (2004) 321–338

Surgical considerations in anal cancer

John Skibber, MD, FACSa,*,Miguel A. Rodriguez-Bigas, MD, FACSa,Philip H. Gordon, MD, FRCSC, FACSb,c

aDepartment of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center,

1515 Holcombe Boulevard, Unit 444, Houston, TX 77030, USAbDepartment of Colon and Rectal Surgery, Sir Mortimer B. Davis–Jewish General Hospital

3755 Cote Sainte Catherine Road, No. G-314, Montreal, Quebec H3T 1E2, CanadacDepartment of Surgery, McGill University, 845 Sherbrooke Street W, Montreal,

Quebec, Canada, H3A 2T5

Neoplasms in the perianal region and anal canal are uncommon. In anydiscussion of neoplasms in this region, it is imperative to have a clearunderstanding of their location and pathology; however, confusion exists inthis area. The lack of precision in reporting the exact location of a lesion orthe inclusion of perianal and anal canal malignancies makes it inappropriateto compare the results of different forms of therapy from one series toanother, because these series often compare dissimilar lesions.

Differentiation between perianal and anal canal neoplasms

To enable the reader to have a better understanding of the classification,a brief review of the anatomy is appropriate. The anatomy of the anal canalis described in more detail elsewhere in this issue. The anal canal, whichextends from the anorectal ring to the anal verge, is lined with differentkinds of epithelium [1]. Below the dentate line is squamous epithelium;above the dentate line is columnar epithelium. This junction is not abrupt;for a distance of 6 to 12 mm above the dentate line, there is an area wherecolumnar, cuboidal, transitional, or squamous epithelium may be found.This area, often referred to as the cloacogenic zone, has been considered toconsist of unstable epithelium, and, because of its diversity, this epitheliumgives rise to a variety of neoplasms. The two areas of the anal canal alsohave different routes of lymphatic drainage, with neoplasms at or above the

* Corresponding author.

E-mail address: [email protected] (J. Skibber).

1055-3207/04/$ - see front matter � 2004 Elsevier Inc. All rights reserved.

doi:10.1016/j.soc.2003.12.006

mailto:[email protected]

322 J. Skibber et al / Surg Oncol Clin N Am 13 (2004) 321–338

dentate line draining cephalad by way of the superior rectal lymphatics tothe inferior mesenteric nodes and laterally along both the middle rectalvessels and inferior rectal vessels through the ischioanal fossa to the internaliliac nodes. Lymph from the anal canal below the dentate line usually drainsto the inguinal lymph nodes. If obstruction exists, however, lymph can drainto the superior rectal nodes or along the inferior rectal lymphatics to theischioanal fossa.

To standardize the nomenclature, the World Health Organization andthe American Joint Committee on Cancer have developed a universallyagreed-on descriptive terminology for the histologic typing of intestinalneoplasms of the anal region [2,3]. According to their terminology, ‘‘Theanal canal extends from the upper to the lower border of the internal analsphincter (from pelvic floor to anal verge). The mucosal lining is divided intothree zones: upper or colorectal, middle or transitional, and lower orsquamous. The transitional zone extends upwards from the dentate line fora distance of approximately 1 cm’’ [2]. This definition is in contrast to manyseries in the literature that use the dentate line as the dividing line describingthe anal canal as the area above the dentate line and the anal margin as thearea below the dentate line [4–7]. Numerous other reports never define thelandmarks. The perianal skin [8,9]—that is, the junction of the hair-bearingskin and the modified skin (anoderm) of the anal canal—or more distal isstaged according to the system used for skin carcinomas. The lateral ordistal extent of the perianal skin is not mentioned by the committee, but it isreasonable to define it as 5 to 6 cm from the anal verge, as suggested bysome authors [9,10]. Box 1 lists a classification of neoplasms of the analregion.

This article discusses the operative treatment of anal margin neoplasmsand squamous cell carcinoma (SCC) of the anal canal, whereas managementof other entities is addressed by other authors in this issue. Much of thefollowing information has been obtained from previous publications [11,12].

Anal margin neoplasms

Squamous cell carcinoma

SCCs of the anal margin resemble those occurring in skin elsewhere in thebody. Macroscopically, they typically have rolled, everted edges with centralulceration. They vary in size from less than 1 cm to lesions that almostobstruct the anal orifice. The male-to-female incidence ratio is approxi-mately equal, and the average age of patients is between 62 and 70 years[8,13].

Despite its external location, SCC of the anal margin is usually diagnosedlate; more than 50% of patients have a delay in diagnosis of 2 years afteronset of symptoms [14]. In 25% of patients, the carcinoma will have reached5 cm by the time of diagnosis [13,15]. The usual presenting symptom is

323J. Skibber et al / Surg Oncol Clin N Am 13 (2004) 321–338

a persistent lump that has increased in size, but bleeding and pruritus andpain, tenesmus, and incontinence may occur [8]. On rare occasions, SCCpresents as a perianal abscess [16]. Up to 28% of patients who have perianalSCC are misdiagnosed as having hemorrhoids, an anal fissure, an analfistula, atopic eczema, an anorectal abscess, or a benign neoplasm [10].Histologically, these carcimonas are usually well-differentiated, keratinizedlesions. They are slow growing and spread mainly to inguinal lymph nodes.

Most authors recommend wide local excision as the treatment of choice.The results from several series of cases are reported in Table 1.

For less favorable lesions, chemoradiation has been recommended[13,21–24]. Residual or recurrent carcinoma after radiation can be treatedwith local excision or an abdominoperineal resection (APR). Prophylacticradiation to the groin is also recommended, particularly for T2 and T3

Box 1. Classification of anal carcinomas

Anal margin neoplasmsSquamous cell carcinomaBasal cell carcinomaBowen’s diseasePerianal Paget’s diseaseVerrucous carcinomaKaposi’s sarcoma

Anal canal neoplasmsSquamous cell carcinoma

Epidermoid carcinomaBasaloid (cloacogenic)Mucoid epidermoid carcinoma

AdenocarcinomaRectal typeGlands and ductsAnorectal fistula

MelanomaSarcoma

Table 1

Results of local excision of squamous cell carcinoma of the anal margin

First author Year No. patients Local recurrence (%) 5-y survival (%)

Beahrs [17] 1976 27 — 100

Al Jurf [18] 1979 10 50 90

Schraut [19] 1983 11 — 82

Greenall [15] 1985 31 42 68

Jensen [20] 1988 32 63 —


lesions [13,21]. For extensive lesions invading the underlying sphinctermuscle, it has been suggested that APR offers the best form of local controland the best rates of survival [15,17].

Mendenhall et al [25] reported on 16 patients who had T2 and T3 analmargin SCCs treated with radiotherapy alone or radiotherapy plus che-motherapy. At a 2-year follow-up, all patients were disease-free. The authorsbelieve T1 and T2 lesions can be successfully treated with radiotherapy aloneor local excision. Because T2 lesions have a significant risk of inguinal lymphnode metastases, these authors believe treatment should consist of radiother-apy to the primary carcinoma in conjunction with elective inguinal lymphnode irradiation. More advanced lesions are best treated with combinedradiotherapy and concomitant chemotherapy. APR should be reserved forthose patients who present with fecal incontinence or those with locallyrecurrent disease after previous radiotherapy.

For the 8% to 40% of patients in whom synchronous metastases toinguinal lymph nodes develop, a groin dissection should be performed[3,25,26]. Overall, local excision and APR have high failure rates because oflocal recurrence, inguinal node metastasis, and distant metastasis [13,22,23].

Basal cell carcinoma

Basal cell carcinomas of the anal margin comprise 0.2% of all anorectalneoplasms [26]. Memorial Sloan-Kettering Cancer Center in New York haslisted only five patients with this type of neoplasm in the past 25 years [27].

These carcinomas occur more frequently in men than in women andusually occur in the sixth decade of life. They are usually 1 to 2 cm indiameter and are characterized by a central ulceration with a raised pearlyborder. They have a low invasive potential and rarely metastasize.Histologically, they are similar to basal cell carcinomas of skin elsewhereand should be differentiated from basaloid carcinomas [28].

The treatment of choice is wide local excision, and, even in patients inwhom local recurrence develops, re-excision can be performed [28]. Localrecurrence after local excision is common; Nielsen and Jensen [26] reportedthat 29% of patients in a series of 27 patients experienced local recurrenceafter local excision, and they recommended re-excision as treatment.Paterson et al [29] reviewed 21 patients with a mean age of 67 years. Witha mean follow-up time of 72 months, 17 of the patients available for follow-up with local excision demonstrated no local recurrence. APR of the rectumshould be considered only for the neglected case where the lesion extendsinto the anal canal and the deep surrounding tissues. Even then,radiotherapy might be tried before attempting an APR. The crude 5-yearsurvival rate reported in the largest series of patients who had perianal basalcell carcinoma was 72.6%, and no deaths were attributed to the carcinoma.


Bowen’s disease

Bowen’s disease is a rare, slow-growing intraepidermal SCC. It occursmost commonly in the fifth and sixth decades of life. Macroscopically, thelesions appear as discrete erythematous, occasionally pigmented, non-infiltrating, scaly or crusting plaques, sometimes exhibiting a moist surface.Foci of ulceration indicate an invasive carcinoma, a complication thatoccurs in approximately 6% of patients [30]. Patients may experienceitching, burning, or bleeding, but the diagnosis is confirmed by biopsy.Characteristic bowenoid cells are seen, which are multinucleated giant cellswith some vacuolization giving a halo effect. In a series by Beck [31], 20% ofthese cases of perianal Bowen’s disease were incidental findings, diagnosedafter pathologic evaluation of tissue removed during hemorrhoidectomy.

The treatment of choice for Bowen’s disease is wide local excision [30–33].Beck and Fazio [34] recommended biopsies be taken 1 cm from the edge ofthe lesion and, if negative, these become the perimeter of the excision. Forsmall lesions, the defect may be closed primarily, but excision of largerlesions may require coverage with split-thickness skin grafts or rotationflaps. If grafting is necessary, the patient is placed on a preoperativemechanical and antibiotic bowel preparation and postoperatively on clearfluids, elemental diet, Imodium (loperamide), and codeine containinganalgesics to prevent bowel movements for approximately 5 days. Evenextensive disease that requires circumferential excision can be repaired withV-Y sliding flaps [35]. If a concomitant invasive anal carcinoma is present,the treatment consists of APR.

Marchesa et al [36] reviewed 47 patients who had perianal Bowen’sdisease: 26 of the patients were treated by wide local excision withmicroscopic clearance of resection margins, 15 were treated by local excisionwith only macroscopic clearance of resection margins, 5 patients weretreated by CO2 laser vaporization, and 1 patient was treated by APRbecause of fecal incontinence. With a median follow-up period of 104months, the incidence of local recurrence was 23% after wide local excision,53% after local excision and 80% after CO2 laser vaporization. The authorsconcluded that wide local excision for perianal Bowen’s disease leads toa significantly lower recurrence rate than local excision or laser therapy.Sarmiento et al [37] reviewed the outcome of 19 patients with perianalBowen’s disease. No associated carcinomas were found. Wide resection,including V-Y flaps, were performed in 18 patients, who did not experiencedysfunction. The 1-year and 5-year recurrence rates were 16% and 31%,respectively. Recurrence was treated in all but one case by wider resection.The 5-year survival rate was 75%. The authors noted that, despite the highrate of recurrence, perianal Bowen’s disease can be treated by local excision.Cleary et al [38] surveyed the membership of the American Society of Colonand Rectal Surgeons (ASCRS) in an effort to determine currentmanagement practices in the care of patients who have perianal Bowen’s


disease. Wide local excision was performed by 96% of the respondents forsmall lesions (�3 cm) and by 87% of respondents for large lesions (�3 cm).Thus, most surgeons perform wide local excision for both small and largelesions. In selected cases, photodynamic therapy has been used with success[39].

The proposed relationship between Bowen’s disease and the simultaneousor subsequent development of an internal malignancy is controversial.Graham and Helwig [39] reported that 70% to 80% of patients withBowen’s disease studied from the time of diagnosis to death had one ormore primary internal malignancies or primary carcinoma of the skin, andinvasive SCC from the original lesion developed in 10% of patients.Metastases reportedly develop in approximately one third of patients unlessadequate treatment is performed. The authors further suggested thatcutaneous premalignant and malignant lesions will develop in 40% ofpatients 6 or 7 years after the onset of Bowen’s disease. In order ofdecreasing frequency, the respiratory tract, gastrointestinal tract, genitouri-nary organs, and reticuloendothelial system are most often implicated. Thisconcept went unchallenged for more than a quarter of a century. Ina subsequent review, Arbesman and Ransohoff’ [40] challenged this viewand argued that most series in the literature do not substantiate the relationbetween Bowen’s disease and the subsequent development of carcinoma inother organs. Marfing et al [33] surveyed the membership of the ASCRS andgathered information on 106 patients. Associated malignancy occurred inonly 4.7% of patients. There was a recurrence rate of 9.4% and invasivecarcinoma developed in another 5.7% of patients. The authors concludedthat extensive investigation is not necessary and that patients’ greatest risk isthe development of recurrent or invasive disease. Chuang et al [41]conducted a matched case-control study to evaluate the significance ofBowen’s disease as a skin marker for internal malignancy. Ninety patientswho had Bowen’s disease were matched by age, gender, race, and date ofbiopsy for diagnosis (or treatment) to 90 other patients chosen as controls.Six patients in the Bowen’s disease group and three patients in the controlgroup had internal malignancy. That study could not substantiate the claimthat Bowen’s disease is a skin marker for internal malignancy.

Perianal Paget’s disease

Among the locations where extramammary Paget’s disease may be foundis the perianal skin. It is an intraepithelial adenocarcinoma with a longpreinvasive phase, but, if the patient lives long enough, an adenocarcinomaof the underlying aprocine gland type will develop [42]. This condition isextremely rare, most commonly found in elderly people in the sixth andseventh decades of life. Complaints include perianal itching, bleeding,occasionally a palpable mass, weight loss, and mucous discharge [43].


Macroscopically, it consists of a slowly enlarging erythematous, eczema-tous, and often sharply demarcated rash that may be oozing or scaling. Thedisease is often associated with intractable pruritus. The entire circumfer-ence of the anus may be involved in up to one third of cases [26]. Thedefinitive diagnosis is made by biopsy, which shows the characteristic Pagetcells, which are large, pale, vacuolated cells with hyperchromatic eccentricnuclei. They are highlighted with a periodic acid-Schiff stain because of thehigh mucin content. They also contain mucoproteins that stain with alcianblue, a characteristic that helps differentiate the condition from Bowen’sdisease. Coexisting visceral malignancies have been reported to occur in38% to 86% of series in the literature (Table 2), and therefore a completelarge bowel investigation should be performed. Described areas ofinvolvement for carcinoma include large bowel and anus, skin, prostate,nasopharynx, and neck [44].

The treatment of choice is wide local excision. Because the disease mayextend beyond the gross margins, Beck and Fazio [45] have recommendedmapping the extent of involvement by multiple biopsies, 1 cm from the edgeof the lesion. Another practical aid at the operating table is the use ofsupravital staining of Paget cells. Using this technique, the entire area ofskin is washed with acetic acid (1%–2%). The whole area is painted withtoluidine blue and once again washed with acetic acid. The nuclei of thePaget cells pick up the toluidine blue, but the blue of the lesion is not washedaway with the second washing of acetic acid. Multiple punch biopsies areperformed 1 to 2 cm from the lesion. If these are negative, this becomes theline of excision. If the lesion is small, primary closure may be performed, butwith larger lesions, a split-thickness skin graft may be required. A recurrencemay be re-excised.

Marchesa et al [46] reviewed 14 patients with perianal Paget’s disease whowere followed up for 5 years or longer following operative treatment. Fourpatients were excluded because of progression of invasive malignancy at thetime of diagnosis. A local excision was performed in two patients, withmacroscopic clearance of the operative margins. The remaining eightpatients underwent wide local excision (ie,[1 cm of microscopic clearance

Table 2

Malignancy associated with perianal Paget’s disease

First

author Year

No.

patients

Average

age (y)

Associated

malignancy (%)

Helwig [45] 1963 14 62 86

Arminski [58] 1973 32 64 78

Beck [47] 1987 10 64 50

Jensen [44] 1988 22 — 32

Goldman [59] 1992 5 64 80

Sarmiento [49] 1997 13 68 38

McCarter [50] 2003 27 63 44


of the surgical margins). The actuarial 8-year recurrence rates for patientstreated with local excision and wide local excision were 100% and 50%,respectively. All four patients with recurrence after wide local excision weresuccessfully treated, with no further recurrence with a second wide localexcision. The authors concluded that survival of patients with perianalPaget’s disease treated by wide local excision was higher than those treatedby local excision.

Sarmiento et al [47] reviewed the results of 13 patients with a meanfollow-up of 6.7 years. Eleven patients underwent local resection. Almost allrecurrences were treated with wider local excision. The 5-year recurrencerate was 61%, with an overall 5- and 10-year survival rate of 67%. Theyfound that both primary and recurrent lesions are amenable to treatment bywider local resection.

The most recent report on the long-term outcome of the treatment ofperianal Paget’s disease was by McCarter et al [48], who summarized thehistory and treatment of all patients diagnosed with perianal Paget’s diseaseover a 50-year period. They reported on 27 patients with a median age of 63years. Wide excision was the treatment for 74% of patients. Localrecurrence developed in 37% of patients. An invasive component wasidentified in 44% of patients. A colostomy was deemed necessary in 22% ofpatients and adjuvant chemoradiotherapy was used in another 22% ofpatients who had more aggressive disease. At a median follow-up time of 67months, 56% of patients had no evidence of disease and two patients died ofmetastatic disease. The overall and disease-free survival rate at 5 years was59% and 64%, respectively, which decreased to 33% and 39%, respectively,at 10 years. The authors concluded that the treatment of choice is wideexcision, and that more extensive operation is reserved for those patientswho have invasive malignancies. The role of chemoradiotherapy for thisdisease remained undefined in this study.

Formore advanced lesionswith underlying carcinoma,APR,with inguinallymph node dissection if positive lymph nodes are present, is necessary.Because of the usual long delay in diagnosis (average, 4 y), approximately25% of patients who have Paget’s disease already have metastases [49,50].The sites of the metastases in order of decreasing frequency are the inguinaland pelvic lymph nodes, liver, bone, lung, brain, bladder, prostate and adrenalgland [50].

For radically treated patients, the 5- and 10-year crude survival rates are54% and 45%, respectively [44]. After adequate excision, for those patientswith no underlying carcinoma, the prognosis is good.

Verrucous carcinoma

Although there is no universal agreement, there is a growing consensus ofopinion that the entity termed a giant condyloma acuminata or a Buschke-


Lowenstein tumor probably represents a verrucous carcinoma [51,52].Macroscopically, the lesion presents as an exophytic, warty, gray-whitesoft to firm mass varying in size from 1 to 10 cm. The cauliflower-like massmay arise in the perianal skin, anal canal, or distal rectum and is frequentlyindistinguishable from more benign lesions. The clinical course of thisgrowth is one of relentless progression and expansion of the neoplasm byextensive erosion and pressure necrosis of surrounding tissues, with invasionof the ischioanal fossa, perirectal tissues, and even the pelvic cavity. Theinvasive nature of the lesion may cause multiple sinuses or fistulous tracks,which may invade fascia, muscle, or rectum and may cause inflammation,infection, and hemorrhage. The extent of involvement can be preciselydetermined by CT examination. Microscopically, the lesions bear a markedresemblance to condyloma acuminata with papillary proliferation, kerati-nization, acanthosis, parakaratosis, and vacuolization of superficial layers.

The extent of surgery should be determined in each individual patient.Gingrass et al [53] recommended wide local excision. If the carcinomainvolves the anal sphincters, APR should be performed. Other authorsbelieve radical surgery, which usually means APR, offers the only hope ofpermanent cure [54]. Currently, there have been no reports on the use ofmultimodality therapy in the treatment of verrucous carcinoma, but suchconsideration may obviate the need for radical extirpative surgery. SCCassociated with condyloma acuminata has been treated effectively withchemoradiation [21]. The difference in the two entities may only be one ofnomenclature [11,55,56].

Kaposi’s sarcoma

Kaposi’s sarcoma is an uncommon malignancy. Chronologically, it hasbeen divided into four types: (1) an indolent form, which may be termedEuropean, Western, or nodular; (2) a florid and more aggressive forminvolving intra-abdominal viscera and lymph nodes, first described duringthe 1950s from equatorial Africa; (3) a form that manifested in the 1970s intransplant patients and others receiving immunosuppressive therapy; and(4) the most recent form reported since 1981 in patients with AIDS [57].Macroscopically, this sarcoma presents as small brown-red to blue-redsmooth nodules that may enlarge in size. Rarely, the perianal skin becomesinvolved. Microscopically, there are proliferations of spindle cells and ofsmall blood vessels, forming vascular slits filled with erythrocytes,hemorrhage, and deposition of hemosiderin.

Kaposi’s sarcoma is very radioresponsive. Brown pigmentation fromhemorrhage may remain permanently at the sites of the lesions. Chemother-apy should be reserved for treatment of generalized Kaposi’s sarcoma. Thedrugs commonly used have been vinblastine, actinomycin D, doxorubicin(Adriamycin), and dacarbazine; however it is uncertainwhich drug is best [57].


Squamous cell carcinoma of the anal canal

Chemoradiation is the treatment of choice for patients who have invasiveSCC of the anal canal. After chemoradiation for invasive SCC of the analcanal, the local control and the 5-year overall survival rates have beenreported to be 61% to 85% and 58% to 92%, respectively [60]. Because ofthese encouraging results, surgery is no longer considered the primarytreatment for this disease. Even though chemoradiation is effective incontrolling and curing invasive SCC of the anal canal, approximately 15%of patients will have persistent disease and an additional 10% to 30% willdevelop recurrent disease [22]. Historically, radical surgery had been theprimary treatment for invasive SCC of the anal, with reports of 30% to 71%5-year survival rates [22,61]. Because of the excellent results obtained withprimary chemoradiation and the avoidance of a permanent colostomy,the surgeon’s role in the management of this disease now has been limited tothe diagnosis and management of persistent or locally recurrent disease.

Diagnosis

As previously discussed, it is imperative that anal canal lesions bedifferentiated from perianal skin lesions because the treatment of choice forthe latter lesions is, in general, wide local excision. It is important that thesurgeon evaluate these patients before the onset of and after completion ofmultimodality therapy to clinically stage the patient and to assess clinicalresponse.

Occasionally, the clinician will encounter a female patient witha rectovaginal mass. SCC of the anal canal must be considered in thedifferential diagnosis of the mass, and the patient examined appropriately. Itis critical that if biopsies of the mass are to be obtained, they should beperformed transrectally, because if the mass is from invasive SCC of the analcanal and biopsies are obtained transvaginally, a potential early-stage tumorwill be converted into a T4 tumor.

It is not clear when to perform biopsies after completion of chemo-radiation. The current authors’ policy has been to follow up the patientsclinically with rectal examinations starting approximately 4 to 6 weeks aftercompletion of therapy. They believe that, even at this time, there will becontinued tumor shrinkage, but patients have to be evaluated to havea baseline examination after primary treatment. Patients are then followedup closely with rectal examinations until either they have a complete clinicalresponse or an abnormal or nonhealing area is noticed. It is at this time thata biopsy is performed. As long as there is clinical improvement, patients areclinically observed. Rarely are biopsies performed before 16 weeks aftertreatment. If there is evidence of persistent disease, consideration is given tofurther chemotherapy or radiation. If there is no clinical response after thistreatment, however, then radical surgery is recommended for persistentdisease.


Management of persistent or recurrent disease

Most authors have defined persistent disease as the diagnosis of persistenttumor or recurrent tumor within the first 6 months after multimodalitytreatment. Recurrent disease has been considered the diagnosis of recurrenttumor at least 6 months after a complete clinical response. Because analcanal cancer is not common and multimodality treatment achieves excellentresults, there are few large-scale series that address these issues. The twolargest series on salvage APR consist of 35 and 38 patients [62,63]. Theprognosis after primary chemoradiation therapy is dire. Table 3 shows theselected series that have been published after salvage APR for failure ofprimary treatment, mainly radiation combined with chemoradiation. Evenafter salvage APR, the prognosis is not good. The overall 5-year survivalrate has been reported to be between 0% and 60%, and the overallrecurrence rate is between 42% and 62% [62–69]. Most important, local(pelvic) recurrence is the most common pattern of failure after salvage APRfor invasive SCC of the anal canal.

Because of the infiltrative nature of SCC of the anal canal, the surgeonhas to realize that recurrences will develop when margins of resection areinvolved with tumor. In several of the series reported in Table 3, there werepositive margins. At the time of surgery, if available, intraoperativeradiation may be used to address the positive margin, but the surgeonmust not rely on this treatment. A positive margin implies a dire prognosis,and if in the preoperative assessment a negative margin would be unlikely tobe obtained with radical surgery, then the salvage procedure should not bedone. The morbidity and potential interference with quality of life outweighthe benefits of any salvage procedure that leads to a less than completeresection with negative margins. Also important, in women, vaginalrecurrence is common after primary APR [70]. Therefore, posteriorvaginectomy should be considered along with salvage APR for recurrentor persistent SCC of the anal canal.

After salvage APR, the major morbidity is related to the perinealwounds. Perineal wound problems, including infection and nonhealingwounds, have been reported to occur in at least 30% to 60% of patientsafter salvage APR [62,70]. The use of musculocutaneous flaps offers tissue toobliterate the pelvic defect and for vaginal reconstruction. Tei et al [71]reported on 14 patients who underwent vertical rectus abdominismusculocutaneous flap reconstruction to cover the perineal defect aftersalvage APR. There were no flap-related complications, and primary healingwas achieved in all 14 patients. If a musculocutaneous flap is not possible,the omentum may be an alternative to obliterate the empty pelvic space.

In summary, the management of persistent or recurrent SCC of the analcanal consists of radical surgery, namely APR (with posterior vaginectomyin women) or exenterative procedures. On extremely rare occasions, localexcision has been reported to be successful, but the current authors believe

Table 3

Results of salvage

Overall LocalOverall survival (%)

First author recurrence (%) Recurrence (%) 3-y 5-y

Longo [64] NS NS — 57

Ellenhorn [62] 61 66a — 44

Pocard [65] 61 NS 72b 60c

29c 0###

Klas [66] 62d

Allal [67] 58 73e 44.5

Van der Wal [68] 62 100f 47

Smith [69] 81 72

Nilsson [63] 42 93 52

Abbreviations: C erior pelvic exenteration; RT, radiotheraphy.a Pelvis.b Persistent disc Recurrent disd Alive and dise Local and regf 5 patients pel

332

J.Skibber

etal/Surg

OncolClin

NAm

13(2004)321–338

surgery for persistent or recurrent cancer

No.

Year Prior therapy patients Procedure

1994 LE, LE + RT, LE + CRT 17 APR

1994 CRT 38 APR

1998 RT 21 APR

1999 CRT 13 APR

1999 RT only, CRT 23/3 APR/LE

2001 CRT 17 (13 ‘‘curative’’) APR/PPE

2001 CRT 22 APR

2002 RT only, CRT 35 APR

RT, chemoradiation; LE, local excision; NS, not significant; PPE, post

ease.

ease.

ease-free, mean follow-up of 32 months.

ional.

vis or groin and 3 patients pelvis and distant.


that the latter procedure is not indicated in the management of persistent orrecurrent SCC of the anal canal. The use of native tissues, such asmyocutaneous flaps, to reconstruct the surgical defect has markedlydecreased the perineal wound morbidity in this group of patients.

Management of lymphatic metastasis from squamous carcinoma

of the anal canal

Anatomy of inguinal and iliac lymph nodes and patternsof lymphatic spread

Lymphatic drainage of the anal canal parallels the arterial blood supply tothe anal canal [72]. Lymphatics of the proximal anal canal drain to theperirectal lymph nodes along the superior and middle rectal vessels and intothe hypogastric nodes. Theymay cross the ischiorectal fossa to the hypogastricnodes. Lymphatics from the lower anal canal distal to the dentate line drainto the superficial and deep inguinal lymph nodes. The staging of analcancers emphasizes the importance of lymph nodes as a significant factor inprognosis.

Lymph node assessment in clinical staging

Lymph node involvement may be heralded by pain in the area of theaffected lymph node basin or by complaints of edema in the affected lowerextremity. The patient may report the development of a mass or ulcerationin the area of advanced affected lymph nodes. Lymph nodes can beidentified by palpation of the inguinal nodal basins. There may be perirectallymph node involvement, which is palpable on rectal examination.Radiologic imaging may identify nonpalpable but enlarged lymph nodesin patients who are difficult to examine or when the lymph nodes are presentwithin the pelvis. The lymph nodes may be sampled in a biopsy procedureby image-guided techniques, if they cannot be sampled by direct fine-needleaspiration (FNA). Open biopsy is rarely indicated as a diagnostic procedureand can have a significant morbidity because of wound infection, seroma, ordraining sinuses in previously irradiated fields. Sentinel lymph node biopsyis being examined as a procedure for the identification of involved lymphnodes. It has been demonstrated that this accurate technique is feasible inanal cancer [73,74].

Clinically evident lymph node metastases at presentation

In patients treated with APR, pelvic lymph node metastases are found inapproximately 30% or more of patient who have T3/T4 disease [75]. The riskof lymph node metastasis increases with increasing T stage of the primarytumor. Because most synchronous lymph nodemetastases are controlled withchemoradiation, this is the initial treatment of choice.


Management of synchronous lymph node metastasis

Studies of surgical lymphadenectomy alone have shown local failure ratesof 20% to 40% [76,77]. There are reports of long-term disease-free intervalsof 60% for patients with inguinal lymph node metastasis managed bylimited groin dissection following 45 Gy of radiation therapy [78]. Othershave reported control of clinically abnormal nodes in 71% of patients whohave had high-dose radiation alone. In addition, perirectal and internal iliaclymph nodes can be controlled in up to 71% of patients who have metastaticlymph nodes [79]. In patients who have persistent disease in the inguinallymph nodes following chemoradiation, inguinal lymph node dissectionshould be considered.

Metachronous lymph node metastasis from squamous carcinomaof the anal canal

In approximately 8% of patients, clinically evident metachronous lymphnode metastases will not be eradicated following radiation therapy. Inhighly selected situations, metachronous lymph node metastasis may requiregroin dissection or APR. Systemic chemotherapy and radiation are usuallythe first line of treatment, however. In a series where metachronous lymphnode metastases were resected after primary APR, the 5-year survival ratewas reported as high as 55% following lymphadenectomy [80]. Thelymphadenectomy can be accompanied by significant morbidity in termsof wound problems related to seromas or infections, however [81].Metachronous lymph node metastases can be documented either by directFNA or lymph node excision. In fields where previous radiation has notbeen performed to tissue tolerance, lymph node metastasis can besuccessfully treated by additional chemotherapy and radiation.

Surgical principles of lymph node dissection

Mesorectal excision should be performed for recurrences in perirectallymph nodes. Dissections of inguinal nodes should be performed withattention to meticulous hemostasis wound drainage to prevent significantwound complications. Ilioinguinal lymph node dissections can be performedwith a higher rate of morbidity from lymphedema and with some degree ofsuccess [82].

Various incisions have been used for both inguinal and iliac lymph nodedissections. The essential element for the incision is to provide adequateexposure of the nodal basin (femoral triangle or iliac/obturator nodes).Inguinal lymph node dissection includes the superficial lymph nodes in thefemoral triangle and Cloquets’s node. Iliac lymph node dissection extendsfrom the aortic bifurcation to the inguinal ligament and can include theobturator lymph node [83].


After dissection, closed suction drains are placed to manage lymphaticfluid. The Sartorius muscle can be rotated over the femoral vessels.Hemostasis and meticulous skin closure help to minimize complications. Inpatients who have previously received radiation therapy, wound manage-ment may include the rotation of musculocutaneous flaps over the operativefield [84,85].

Summary

SCC of the anus is rare; however, the surgeon is bound to encounter someof these patients during his or her career. It is important that the anatomiclocation and the histology be defined because the initial treatment mayinitially differ. Multimodality therapy is the treatment of choice in SCC ofthe anal canal, with surgery reserved for persistent or recurrent tumors.Multimodality therapy can be used selectively in SCC of the perianal skin,especially in large bulky tumors, followed by definitive surgery. Neverthe-less, the initial treatment of perianal neoplasms is surgical therapy. Ingeneral, inguinal node metastases are treated with chemoradiation. In highlyselected patients, groin dissections are performed, but this procedure is notroutine.

References

[1] Nivatvongs S, Gordon PH. Surgical anatomy. In: Gordon PH, Nivatvongs S, editors.

Principles and practices of surgery for the colon, rectum and anus. 2nd edition. St. Louis,

MO: Quality Medical Publishing; 1999. p. 3–39.

[2] Jass JR, Sobin LH. Histologic typing of intestinal tumors. World Health Organization.

2nd edition. New York: Springer; 1989.

[3] Beahrs OH, Henson DE, Hutter RVP, Kennedy BJ, editors. Manual for staging of cancer.

American Joint Committee on Cancer. 4th edition. Philadelphia: JB Lippincott; 1992.

[4] Brown DK, Ogelsby AB, Scott DH, Dayton MT. Squamous cell carcinoma of the anus.

A twenty-five year retrospective. Am Surg 1988;54(6):337–42.

[5] Greenall MJ, Quan SHQ, Urmacher C, DeCosse JJ. Treatment of epidermoid carcinoma

of the anal canal. Surg Gynecol Obstet 1985;161(6):509–17.

[6] Pintor MP, Northover JMA, Nicholls RJ. Squamous cell carcinoma of the anus at one

hospital from 1948 to 1984. Br J Surg 1989;76(8):806–10.

[7] Nigro ND. Multidisciplinary management of cancer of the anus. World J Surg 1987;11(4):

446–51.

[8] Beahrs OH, Wilson SM. Carcinoma of the anus. Ann Surg 1976;184(4):422–8.

[9] Cummings BJ. Editorial. Oncology 1996;10:1853–4.

[10] Jensen SL, Hagen K, Shokouh-Amiri MH, Nielsen OV. Does an erroneous diagnosis of

squamous-cell carcinoma of the anal canal and anal margin at first physician visit influence

prognosis? Dis Colon Rectum 1987;30(5):345–51.

[11] Gordon PH. Current status—perianal and anal canal neoplasms. Dis Colon Rectum 1990;

33(9):799–808.

[12] Nivatvongs S. Perianal and anal canal neoplasms. In: Gordon PH, Nivatvongs S, editors.

Principles and practice of surgery for the colon, rectum and anus. 2nd edition. St. Louis,

MO: Quality Medical Publishing; 1999. p. 447–71.


[13] Papillon J, Chassard JL. Respective roles of radiotherapy and surgery in the manage-

ment of epidermoid carcinoma of the anal margin. Dis Colon Rectum 1992;35(5):

422–9.

[14] Moller C, Saksela E. Cancer of the anus and anal canal. Acta Chir Scand 1970;136(4):

340–8.

[15] Greenall MJ, Quart SH, Stearns MW, Urmacher C, Decosse J. Epidermoid cancer of the

anal margin: pathologic features, treatment, and clinical results. Am J Surg 1985;149(1):

95–101.

[16] Nelson RL, Prasad L, Abcarian H. Anal carcinoma presenting as a perianal abscess or

fistula. Arch Surg 1985;120(5):632–5.

[17] Beahrs OH, Wilson SM. Carcinoma of the anus. Ann Surg 1976;184(4):422–8.

[18] Al-Jurf AS, Turnbull RB, Fazio VW. Local treatment of squamous cell carcinoma of the

anus. Surg Gynecol Obstet 1979;148(4):576–8.

[19] Schraut WH, Wang CH, Dawson PJ, Block GE. Depth of invasion, location, and size of

cancer of the anus dictate operative treatment. Cancer 1983;51(7):1291–6.

[20] Jensen SL, Hagen K, Harling H, Shokouh-Amiri MH, Nielsen OV. Long-term prognosis

after radical treatment for squamous-cell carcinoma of the anal canal and anal margin. Dis

Colon Rectum 1988;31(4):273–8.

[21] Nigro ND, Vaitkeviceus VK, Herskovic AM. Preservation of function in the treatment of

cancer of the anus. In: de Vita V, editor. Important advances in oncology. Philadelphia: JB

Lippincott; 1989. p. 161–77.

[22] Fuchshuber PR, Rodriguez-Bigas M, Weber T, Petrelli NJ. Anal canal and perianal

epidermoid cancers. Collective review. J Am Coll Surg 1997;185(5):494–505.

[23] Touboul E, Schlienger M, Buffat L, Lefkopoulos D, Yao XG, Par CR, et al. Epidermoid

carcinoma of the anal margin: 17 cases treated with curative-intent radiation therapy.

Radiother Oncol 1995;34(3):195–202.

[24] Cummings BJ, Keane TJ, Hawkins NV, O’Sullivan B. Treatment of perianal carcinoma by

radiation (RT) or radiation plus chemotherapy (RTCT). Int J Radiat Oncol Biol Phys

1986;12:170–3.

[25] Mendenhall WM, Zlotecki RA, Vauthey JN, Copland EM III. Squamous cell carcinoma

of the anal margin treated with radiotherapy. Surg Oncol 1996;5(1):29–35.

[26] Nielsen OV, Jensen SL. Basal cell carcinoma of the anus—a clinical study of 34 cases. Br J

Surg 1981;68(12):856–7.

[27] Quan SHQ. Anal and para-anal tumors. Surg Clin North Am 1978;58(3):591–603.

[28] White WB, Schneiderman H, Sayre JT. Basal cell carcinoma of the anus: clinical and

pathological distinction from cloacogenic carcinoma. J Clin Gastroenterol 1984;6(5):

441–6.

[29] Paterson CA, Young-Fadok TM, Dozios RR. Basal cell carcinoma of the perianal region:

20-year experience. Dis Colon Rectum 1999;42(9):1200–2.

[30] Beck DE, Fazio VW, Jagelman DG, Lavery IC. Perianal Bowen’s disease. Dis Colon

Rectum 1988;31(6):419–22.

[31] Beck DE. Paget’s disease and Bowen’s disease of the anus. Semin Colon Rectal Surg 1995;

6:143–9.

[32] Ramos R, Salinas H, Tucker L. Conservative approach to the treatment of Bowen’s

disease of the anus. Dis Colon Rectum 1983;26(11):712–5.

[33] Marfing TC, Abel ME, Gallagher DM. Perianal Bowen’s disease and associated

malignancies: results of a survey. Dis Colon Rectum 1987;30(10):782–5.

[34] Beck DE, Fazio VW. Premalignant lesions of the anal margins. South Med J 1989;82:

470–4.

[35] Hassan I, Horgan AF, Nivatvongs S. V-Y island flaps for repair of large perianal defects.

Am J Surg 2001;181(4):363–5.

[36] Marchesa P, Fazio VW, Oliart S, Goldblum JR, Lavery IC. Perianal Bowen’s disease:

a clinicopathologic study of 47 patients. Dis Colon Rectum 1997;40(11):1286–93.


[37] Sarmiento JM, Wolff BG, Burgart LJ, Frizelle FA, Ilstrup DM. Perianal Bowen’s disease:

associated tumors, human papillomavirus, surgery, and other controversies. Dis Colon

Rectum 1997;40(8):912–8.

[38] Cleary RK, Schaldenbrand JD, Fowler JJ, Schuler JM, Lampman RM. Treatment options

for perianal Bowen’s disease: survey of American Society of colon and Rectal Surgeons

Members. Am Surg 2000;66(7):686–8.

[39] Graham JH, Helwig EB. Bowen’s disease and its relationship to systemic cancer. Arch

Dermatol 1961;83:738.

[40] Arbesman H, Ransohoff DF. Is Bowen’s disease a predictor for the development of internal

malignancy? A methodological critique of the literature. JAMA 1987;257(4):516–8.

[41] Chuang TY, Tse J, Reizner GT. Bowen’s disease (squamous cell carcinoma in situ) as a skin

marker for internal malignancy: a case-control study. Am J Prev Med 1990;6(4):238–43.

[42] Morson BC, Dawson MP. Gastrointestinal pathology. London: Blackwell Scientific; 1972.

[43] Berardi RS, Lee S, Chen HP. Perianal extramammary Paget’s disease. Surg Gynecol

Obstet 1988;167(4):359–66.

[44] Jensen SL, Sjolin KE, Shokouh-Amiri MH, Hagen K, Harling H. Paget’s disease of the

anal margin. Br J Surg 1988;75(11):1089–92.

[45] Beck DE, Fazio VW. Perianal Paget’s disease. Dis Colon Rectum 1987;30(4):263–6.

[46] Marchesa P, Fazio VW, Oliart S, Goldblum JR, Lavery IC, Milsom JW. Long-term

outcome of patients with perianal Paget’s disease. Ann Surg Oncol 1997;4(6):475–80.

[47] Sarmiento JM, Wolff BG, Burgart LJ, Frizelle FA, Ilstrup DM. Paget’s disease of the

perianal region—an aggressive disease? Dis Colon Rectum 1997;40(10):1187–94.

[48] McCarter MD, Quan SH, Busam K, Paty PP, Wong D, Guillem JG. Long-term outcome

of perianal Paget’s disease. Dis Colon Rectum 2003;46(5):612–6.

[49] Grodsky L. Uncommon nonkeratinizing cancers of the anal canal and perianal region.

N Y State J Med 1965;65:894–901.

[50] Helwig EG, Graham JH. Anogenital (extra mammary) Paget’s disease: a clinicopathologic

study. Cancer 1963;16:387–403.

[51] Lee SH, McGregor DH, Kuziez MN. Malignant transformation of perianal condyloma

acuminatum: a case report with review of the literature. Dis Colon Rectum 1981;24(6):

462–7.

[52] Prioleau PG, Santa Cruz MJ, Meyer JS, Bauer WC. Verrucous carcinoma: a light and

electron microscopic, autoradiographic, and immunofluorescence study. Cancer 1980;

45(11):2849–57.

[53] Gingrass PJ, Bubrick MP, Hitchcock CR, Strom RL. Anorectal verrucose squamous

carcinoma: report of two cases. Dis Colon Rectum 1978;21(2):120–2.

[54] Elliot MS, Werner ID, lmmelman EJ, Harrison AC. Giant condyloma (Bushke-

Loewenstein tumor) of the anorectum. Dis Colon Rectum 1979;22(7):497–500.

[55] Nelson H, Dozois RR. Anal neoplasms. Perspect Colon Rectal Surg 1994;7:16–36.

[56] Cintron J. Buschke-Loewenstein tumor of the perianal and anorectal region. Semin Colon

Rectal Surg 1995;6:135–9.

[57] Shiels RA. A history of Kaposi’s sarcoma. J R Soc Med 1986;79(9):532–4.

[58] Arminski TC, Pollard RJ. Paget’s disease of the anus secondary to a malignant papillary

adenoma of the rectum. Dis Colon Rectum 1973;16(1):46–55.

[59] Goldman S, Ihre T, Lagerstedt U, Svensson C. Perianal Paget’s disease: report of five

cases. Int J Colorectal Dis 1992;7(3):167–9.

[60] Ryan DP, Mayer RJ. Anal carcinoma: sitology, staging, epidemiology, treatment. Curr

Opin Oncol 2000;12(4):345–52.

[61] Gordon PH. Squamous cell carcinoma of the anal canal. Surg Clin North Am 1988;68(6):

1391–9.

[62] Ellenhorn JDI, Enker WE, Quan SHQ. Salvage abdominoperienal resection following

combined chemotherapy and radiotherapy for epidermoid carcinoma of the anus. Ann

Surg Oncol 1994;1(2):105–10.


[63] Nilsson PJ, Svensson C, Goldman S, Glimelius B. Salvage abdominoperineal resection in

anal epidermoid cancer. Br J Surg 2002;89(11):1425–9.

[64] Longo WE, Vernava AM III, Wade TP, Coplin MA, Virgo KS, Johnson FE. Recurrent

squamous cell carcinoma of the anal canal: predictors of initial treatment failure and

results of salvage therapy. Ann Surg 1994;220(1):40–9.

[65] Pocard M, Tiret E, Nugent K, Dehni N, Parc R. Results of salvage abdominoperineal

resection for anal cancer after radiotherapy. Dis Colon Rectum 1998;41(12):1488–93.

[66] Klas JV, Rothenberger DA, Wong WD, Madoff RD. Malignant tumors of the anal canal:

the spectrum of disease, treatment, and outcomes. Cancer 1999;85(8):1686–93.

[67] Allal AS, Laurencet FM, Reymond MA, Kurtz JM, Marti MC. Effectiveness of surgical

salvage therapy for patients with locally uncontrolled anal carcinoma after sphincter-

conserving treatment. Cancer 1999;86(3):405–9.

[68] van der Wal BCH, Cleffken BI, Gulec B, Kaufman HS, Choti MA. Results of salvage

abdominoperineal resection for recurrent anal carcinoma following combined chemo-

radiation therapy. J Gastrointest Surg 2001;5(4):383–7.

[69] Smith AJ, Whelan P, Cumming BJ, Stern HS. Management of persistent or locally

recurrent epidermoid cancer of the anal canal with abdominoperineal resection. Acta

Oncol 2001;40(1):34–6.

[70] Singh R, Nime F, Mittelman A. Malignant epithelial tumors of the anal canal. Cancer

1981;48(2):411–5.

[71] Tei TM, Stolzenburg T, Buntzen S, Laurberg S, Kjeldsen H. Use of transpelvic rectus

abdominis musculocutaneous flap for anal cancer salvage surgery. Br J Surg 2003;90(5):

575–80.

[72] Wade DS, Herrera L, Castillo NB, Petrelli NJ. Metastases to the lymph nodes in

epidermoid carcinoma of the anal canal studied by a clearing technique. Surg Gynecol

Obstet 1989;169(3):238–42.

[73] Peley G, Farkas E, Sinkovics I, Kovacs T, Keresztes S, Orosz Z, et al. Inguinal sentinel

lymph node biopsy for staging anal cancer. Scand J Surg 2002;91(4):336–8.

[74] Rabbitt P, Pathma-Nathan N, Collinson T, Hewett P, Rieger N. Sentinel lymph node

biopsy for squamous cell carcinoma of the anal canal. Aust NZ J Surg 2002;72(9):651–4.

[75] Gerard JP, Chapset O, Samiei F, Morignat E, Isaac S, Paulin C, et al. Management of

inguinal lymph node metastases in patients with carcinoma of the anal canal: experience in

a series of 270 patients treated in Lyon and review of the literature. Cancer 2001;92(1):77–84.

[76] Stearns MW Jr, Urmacher C, Sternberg SS, Woodruff J, Attiyeh F. Cancer of the anal

canal. Curr Probl Cancer 1980;4(12):1–44.

[77] Boman BM, Moertel CG, O’Connell MJ, Scott M, Weiland LH, Beart RW, et al.

Carcinoma of the anal canal: a clinical and pathologic study of 188 cases. Cancer 1984;

54(1):114–25.

[78] Papillon J, Montbarbon JF. Epidermoid carcinoma of the anal canal. A series of 276 cases.

Dis Colon Rectum 1987;30(5):324–33.

[79] Mitchell SE, Mendenhall WM, Zlotecki RA, Carroll RR. Squamous cell carcinoma of the

anal canal. Int J Radiat Oncol Biol Phys 2001;49(4):1007–13.

[80] Greenall MJ, Magill GB, Quan SH, DeCosse JJ. Recurrent epidermoid cancer of the anus.

Cancer 1986;57(7):1437–41.

[81] Humphrey LJ. Reducing leg edema after groin dissection. J Surg Oncol 1992;50(1):19.

[82] Spratt J. Groin dissection. J Surg Oncol 2000;73:243–62.

[83] Johnson DE, Ames FC. Surgical anatomy and lymphatic drainage of the ilioinguinal

region. Groin Dissection1985;1–20.

[84] Zografos GC, Karakousis CP. Repair after radical groin dissection. J Surg Oncol 1999;

71(2):117–9.

[85] Kuwahara M, Hatoko M, Okazaki T, Shiba A, Tanaka A, Muramatsu T, et al. Coverage

of a defect after groin dissection using a pedicled rectus abdominis musculocutaneous flap.

Ann Plast Surg 1998;41(2):222–3.

surgical considerations in anal cancer

Documents