A.V. Hayman
A.L. Halverson
Presentation
A 68-year-old female presents to her primary care physician (PCP) with complaints of anal pain and itching. Her past medical history is notable for a history of cervical dysplasia. Ten years prior, she underwent a hysterectomy for uterine fibroids. Her last colonoscopy was 18 years ago. Five months ago, the patient started experiencing anal pain with bowel movements and itching. Her PCP diagnosed her with an anal fissure and she was started on stool softeners and psyllium husk powder. A month later, the patient returned to her PCP with worsening symptoms, and she was prescribed topical nifedipine cream. A month later, the patient returned with no relief. Her PCP then referred patient to your clinic with the presumptive diagnosis of a chronic, nonhealing anal fissure.
Differential Diagnosis
Anal pathology is common in the general population. A thorough history can help differentiate between the most common problems, such as internal or external hemorrhoids, anal fissure, anal fistula, and pruritus ani. Anal fissures present primarily with sharp pain during defecation and are often associated with spotting of bright red blood on the toilet paper. Internal hemorrhoids may cause painless rectal bleeding. Thrombosed external hemorrhoids cause a constant pain that persists for several days. Pruritus ani may be caused by rectal mucosal prolapse or irritation from external hemorrhoidal skin tags. Pruritus has also been attributed to dietary irritants, such as citrus, caffeine, spicy foods, tomatoes, or milk. In the absence of other contributing pathology, the treatment for pruritus ani is supportive and includes avoidance of exacerbating factors.
Anal symptoms are often attributed to “hemorrhoids” without further workup, potentially leading to a delay in therapy for an undiagnosed malignancy. Any anal complaint in a high-risk patient, that is, age 50 or older, HIV seropositivity, history of anal or gynecologic human papillomavirus (HPV) or colorectal adenomas, or a relevant family history, should prompt endoscopic evaluation to rule out malignancy. For average-risk individuals, symptoms that persist more than 6 weeks with diet and/or medical therapy warrant endoscopic examination. Initial evaluation should include a complete history and physical exam, including digital rectal exam and anoscopy. Examination under anesthesia should be performed in individuals with persistent symptoms who are unable to tolerate anoscopy in the office.
For the patient in our scenario, during her appointment, you identify a 2-cm area of induration in the anal canal on digital rectal exam. Anoscopy identified ulceration overlying the area of induration. The ulcer was biopsied, and histology confirmed squamous cell carcinoma.
Workup
The patient should undergo a thorough physical examination. Particular attention should be paid to inguinal lymph node evaluation. Any lymphadenopathy should prompt a fine needle aspiration to rule out regional lymph node involvement. Indication for colonoscopy should be based on established colorectal cancer screening guidelines, beginning at age 50 (or earlier if a first-degree relative has a history of colon cancer or polyps) or if the patient is symptomatic.
In order to assess for distant metastases, the patient should undergo an abdominal/pelvic CT (or MRI) and a chest radiograph (or chest CT), although it should be noted that most lymph node metastases are small and may not be able to be detected by cross-sectional imaging. In some cases, a PET-CT may be obtained. HIV status should be ascertained. Evaluation for gynecologic dysplasia should be performed in females as well, since the same pathogen, the HPV, is implicated in both neoplastic processes (Table 1).
TABLE 1. Staging of Anal Canal Carcinoma
The patient in our scenario underwent computed tomography of the abdomen and the pelvis, which showed no evidence of regional or distant metastases. There was no inguinal lymphadenopathy detected on physical examination. Colonoscopy revealed only hyperplastic polyps.
Diagnosis and Treatment
Initial treatment for squamous cell carcinoma of the anal canal is nonsurgical, and consists of combined chemotherapy and radiation. Initial nonsurgical treatment is the standard of care because of the high response rate and the high rate of sphincter preservation. The standard protocol consists of 45 Gy in 25 fractions over 5 weeks to the primary cancer. 5-fluorouracil (5-FU) is infused on days 1 to 4 and 29 to 32 with mitomycin C bolus on days 1 and 29. Systemic treatment for metastatic disease consists of 5-FU and cisplatin.
It is important to distinguish between squamous cell carcinomas of the squamous epithelial-lined anal canal (proximal to the anal verge), which are approached as outlined above, as opposed to the epidermis-lined anal margin (distal to the anal verge). For anal margin cancers, superficial, localized lesions (T1) are treated initially by wide local excision with negative margins. If margins are positive, reexcision is recommended if anatomically feasible; otherwise, the patient should be referred for adjuvant therapy as above. All other therapies follow the above guidelines.
For the patient in our scenario, given the absence of distant metastases, the patient was referred for chemoradiation, which she successfully completed. The patient returned 6 weeks after completion of chemoradiation. Due to residual anal pain, the patient was taken for an examination under anesthesia. The exam identified an area of residual induration. Biopsy of this area revealed residual squamous cell cancer.
Residual tumor may continue to regress for up to 12 weeks following completion of chemoradiation. Repeat examination with biopsy of any residual mass should be performed at 12 weeks to confirm residual disease. If progression of disease is identified at the first follow-up examination, proceeding directly to surgery is appropriate.
The patient in our scenario returns for repeat examination 6 weeks later, 12 weeks after completion of chemoradiation. Residual cancer is confirmed by biopsy of a persistent mass. The patient is recommended to undergo an abdominoperineal resection.
Preoperative Consideration
1. Stoma marking by a certified stomal therapist
2. Perioperative antibiotics
3. Venous thromboembolism prophylaxis
Surgical Approach
When performing an abdominoperineal resection in patients who have been treated with pelvic radiation, a myocutaneous flap should be considered to facilitate wound healing (Table 2). The procedure is commonly performed with the patient in the lithotomy position. Mobilization of the distal colon and rectum and division of the mesentery may be performed using an open technique or laparoscopically when a rectus abdominus muscle flap is not being used. The surgical approach should include careful dissection to maintain the anatomic planes and preserve the peritoneal envelope around the mesorectum. Careful dissection avoids nerve injury that may result in sexual dysfunction. The mesentery should be divided at the proximal superior mesenteric vascular pedicle. Once the pelvic floor is reached, dissection is performed from the perineal approach continuing cephalad to meet the intraabdominal portion of the dissection. Care should be taken to maintain a wide dissection through the levator muscles. Grossly close margins may be sent for frozen section evaluation. After resection of the specimen, the muscle flap is placed into the pelvis. The perineal defect is closed in several layers with absorbable suture, including absorbable suture in the skin to avoid uncomfortable suture or staple removal postoperatively.
TABLE 2. Key Technical Steps for Surgical Management of Anal Cancer
An alternative approach is to perform the abdominal portion of the procedure in the supine position. After creation of the colostomy and closure of the abdominal incision, the patient is turned prone for the completion of the perineal portion of the procedure. Inguinal node dissection should be considered for residual disease in the inguinal lymph nodes.
Postoperative Management
All anal canal cancer patients should be examined every 3 to 6 months for 5 years. Surveillance examination should include inguinal node examination and anoscopy. Anoscopy with topical acetic acid should be considered to survey for recurrent HPV-related dysplasia. For T3+ or N1+ lesions, annual chest/abdominal/pelvis imaging is also recommended for the first 3 years.
Special Intraoperative Considerations
If metastatic disease in encountered at the time of surgery, proceeding with abdominoperineal resection may be appropriate for palliation of symptoms from local disease.
TAKE HOME POINTS
· Anal bleeding that does not respond to medical management should be assessed via anoscopy and/or colonoscopy.
· The first-line treatment for nonmetastatic anal canal carcinoma is nonsurgical.
· Allow up to 12 weeks for regression of lesion after chemoradiation prior to proceeding with surgical resection.
· Abdominoperinal resection is indicated if combined chemoradiation fails.
SUGGESTED READINGS
Abbott DE, Halverson AL, Wayne JD, et al. The oblique rectus abdominal myocutaneous flap for complex pelvic wound reconstruction. Dis Colon Rectum. 2008;51(8):1237–1241.
Garrett K, Kalady MF. Anal neoplasms. Surg Clin North Am. 2010;90(1):147–161.
Hojo K, Vernava III AM, Sugihara K, et al. Preservation of urine voiding and sexual function after rectal cancer surgery. Dis Colon Rectum. 1991;34(7):532–539.
Meyer J, Willett C, Czito B. Current and emerging treatment strategies for anal cancer. Curr Oncol Rep. 2010;12(3):168–174.
NCCN GuidelinesTM Version 2.2011 ACC. www.nccn.org. Accessed June 17, 2011.