WHENEVER technically possible, surgery remains the cornerstone of treatment of anal sac carcinoma (ASC). Other treatment modalities include radiotherapy and chemotherapy, but the role of these treatments has not been clearly determined yet.
Pre-operative medical support is provided as required. In particular, severe hypercalcaemia of malignancy (HM; i.e. calcium >180mg/L) should be considered a medical emergency, as it can have severe consequences such as irreversible impairment of renal function.
Management of HM is beyond the scope of this text and is widely detailed elsewhere 1-3. Briefly, it is treated with a combination of fluid therapy (0.9% NaCl), loop-diuretics (furosemide) once dehydration is corrected, steroids (only after the cause of HM has been diagnosed) and, for extreme or refractory cases, calcitonin and bisphosphonates.
Surgery
Surgery must aim at decreasing the tumour burden as much as possible, especially in hypercalcaemic patients. This is achieved by resecting the primary tumour as completely as possible, as well as by surgically removing metastatic lymph nodes. The latter is usually performed in a first surgical step before resection of the primary tumour, in the same anaesthetic time.
Enlarged abdominal lymph nodes are excised through a midline laparotomy. The entire abdominal cavity is inspected and suspicious lesions, especially of the liver and spleen, are biopsied.
The medial iliac and hypogastric lymph nodes are then localised by palpation. When metastatic, they palpate as hard, lobular and fixed structures. The medial iliac lymph nodes are located laterally to the caudal-most portions of the aorta and caudal vena cava.
The hypogastric lymph node is located immediately caudally to the aortic quadrifurcation, between the internal iliac arteries and veins, ventrally to the median sacral artery and vein.
All enlarged lymph nodes are excised through a combination of sharp, blunt and digital dissection. Lowgrade, diffuse bleeding is commonly encountered during this dissection. The use of electrocautery, especially bipolar, or to an even greater extent vessel-sealing devices help to minimise this bleeding.
When the lymph nodes are extremely enlarged, invasive or excessively adherent to surrounding tissues, placement of Rumel tourniquets on the large vessels in their vicinity may help control accidental lesions to these large vessels.
When lateral sacral lymph nodes are enlarged, their dissection is usually best achieved in two stages. From the abdominal approach, their cranial border is dissected and freed, but the nodes are left in place in view of being excised during the perineal step of surgery.
Neoplastic anal sacs are removed through a perineal approach. Bilateral disease is uncommon (approximately 10% of cases), but some surgeons will also remove unaffected anal sacs during this step.
Excisions of ASCs are in essence marginal, as anal sacs are partially surrounded by loose connective tissues, preventing en-bloc excisions. In addition, there seems to be little rationale for seeking wide margins, as this could only be achieved at the expense of delicate structures such as the rectum and may therefore inappropriately increase the risk for severe post-operative complications.
Marginal or incomplete resections may expose to an increased risk of recurrence, but do not seem to negatively affect survival times 4 and repeating marginal resections is possible. Therefore, the tumour is resected with only a thin layer of muscle fibres from the external anal sphincter muscle.
The dissection progresses cranially along the lateral aspect of the sac until its cranial border is reached. The sac is then progressively retracted caudally, until it is only attached along its contact with the internal anal sphincter muscle and rectal wall.
In most cases, a dissection plane can be found between the rectal wall and the sac, allowing preservation of the wall. In rare cases, the rectal wall is invaded and must be partially resected with the tumour.
Once the tumour is excised, the caudal border of any enlarged lateral sacral lymph nodes is dissected and these nodes are excised.
Complications are uncommon and most commonly involve wound complications. Persistent faecal incontinence should not occur if proper technique is used, unless most of the external anal sphincter is resected.
Adjuvant treatments
Radiation can be used as a neoadjuvant or adjuvant treatment, both on the primary tumour and metastatic lymph nodes. However, irradiation of the perineum and pelvic cavity must be cautious as exposure of the rectum to radiation leads to acute (e.g. colitis, tenesmus) or late adverse effects (e.g. rectal strictures or perforations, incontinence) in up to 50% of cases.
Fractionated protocols using smaller doses (<3Gy) per fraction appear preferable to hypofractionated protocols to limit such complications, which in any case are most often transient and easily managed. There is, however, insufficient evidence to determine objectively the efficacy of radiotherapy, either alone or as an adjuvant, in the treatment of ASCs.
Similarly, the role of adjuvant chemotherapy in the treatment of ASCs remains unclear. Although some studies have concluded that platinum agents are active against ASCs, most failed to demonstrate a benefit 4-6.
A large variety of chemotherapeutic agents have been used for treatment of ASCs, including cisplatin, carboplatin, doxorubicin, epirubicin, mitoxantrone, melphalan and actinomyin D. Given the high metastatic nature of ASCs, we recommend the use of adjuvant chemotherapy, although definitive evidence of its benefits are so far lacking.
Follow-up and prognosis
Post-operatively, blood calcium levels are monitored. When the patient is hypercalcaemic before surgery, its calcaemia is expected to normalise rapidly after surgery if enough of the tumour burden has been removed. If the pre-operative hypercalcaemia is chronic, transient hypocalcaemia can be observed.7
The long-term follow-up is tailored to every patient but typically consists of combinations of serial rectal palpations, abdominal ultrasound scans, chest x-rays and CT scans, every three to six months, for the rest of the animal’s life.
Blood calcium levels are also monitored. Recurrence of hypercalcaemia is usually indicative of either tumour recurrence or significant development of metastatic disease.
Repeat surgery can be considered when additional metastatic lymph nodes develop months to years after the initial surgery, especially if they lead to recurrent hypercalcaemia.
With surgery alone, survival times of about one year have been reported, which are increased by surgical removal of metastatic lymph nodes. 5,8 Chemotherapy would also be expected to increase survival, but data objectively supporting its efficacy are lacking.
In a recent study of 42 cases treated by a combination of surgery and potentially chemotherapy (one case also had radiotherapy), the median survival times were 422 days and 529 days, and the disease-free intervals were 197 days and 529 days, for dogs with and without regional lymphadenopathy, respectively.4
The presence of HM was initially considered a negative prognostic factor, but this has not been confirmed by a number of Figure 2. Excision of a right anal sac carcinoma, intraoperative views: a (left) – marginal dissection of the caudal aspect of the tumour; b – dissection is carried out cranially along the lateral aspect of the tumour until it can be rotated caudally, exposing the rectal wall (arrow), from which it is progressively detached by a combination of blunt and sharp dissection. more recent studies. Unsurprisingly, higher tumour stages have been repeatedly associated with poorer outcomes: the presence of a larger primary tumour (more than 10cm in diameter), regional lymphadenopathy and distant metastasis have all been associated with shorter survival times. 4,5,9
In a recent study using a cut-off value of 4cm in diameter, the size of the primary tumour was not found to influence survival and disease-free interval.4
References
1. Ruthanne, C. (2010) Paraneoplastic syndromes. In: Henry, C. J., Higginbotham, M. L. (eds). Cancer management in small animal practice, volume 1. Maryland Heights, MO, Saunders Elsevier, 94-100.
2. Vail, D. M. (2008) Paraneoplastic hypercalcemia. In: Bonagura, J. D., Kirk, R. W. (eds). Kirk’s current veterinary therapy. XIV (ed 14), volume 1. Philadelphia; London, Elsevier Saunders, 343-347.
3. Bergman, P.J. (2007) Paraneoplastic syndromes. In: Withrow, S. J., Vail, D. M. (eds). Small animal clinical oncology (ed 4), volume 1. St Louis, Saunders Elsevier, 77-94.
4. Potanas, C. P., Padgett, S. and Gamblin, R. M. (2015) Surgical excision of anal sac apocrine gland adenocarcinomas with and without adjunctive chemotherapy in dogs: 42 cases (2005- 2011). Journal of the American Veterinary Medical Association 246: 877-884.
5. Polton, G. A. and Brearley, M.J. (2007) Clinical stage, therapy, and prognosis in canine anal sac gland carcinoma. Journal of Veterinary Internal Medicine 21: 274-280.
6. Bennett, P. F., DeNicola, D. B., Bonney, P. et al (2002) Canine anal sac adenocarcinomas: clinical presentation and response to therapy. Journal of Veterinary Internal Medicine 16: 100-104. 7. Saba, C., Ellis, A. and Cornell, K. (2011) Hypocalcemia following surgical treatment of metastatic anal sac adenocarcinoma in a dog. Journal of the American Animal Hospital Association 47: e173-e177.
8. Hobson, H. P., Brown, M. R. and Rogers, K. S. (2006) Surgery of metastatic anal sac adenocarcinoma in five dogs. Veterinary Surgery 35: 267-270.
9. Williams, L. E., Gliatto, J. M., Dodge, R. K. et al (2003) Carcinoma of the apocrine glands of the anal sac in dogs: 113 cases (1985-1995). Journal of the American Veterinary Medical Association 223: 825-831.
