LARS expert, Katrine Emmertsen, describes a mixed pathophysiological model for LARS in her article submitted for Faecal Incontinence Month.

Functional problems after sphincter preserving treatment of rectal cancer have been known since the 80s. As a result of the TME trials in Sweden (31) and the Netherlands (32) comparing surgery alone with neoadjuvant radiotherapy and surgery identified the magnitude of the functional problems has been recognised. The addition of neoadjuvant radiotherapy significantly increased these risks. LARS is more pronounced in females and in younger patients (33). This cannot be explained by pathophysiological findings alone but may be related to different coping strategies, age and the acceptance of chronic functional problems. A large Danish cohort (34) described the pattern cluster of symptoms now termed Low Anterior Resection Syndrome (LARS) consisting of faecal incontinence, flatulence, frequency of bowel movements, fragmented defecation, and faecal urgency with a significant negative impact on quality of life (Table 2). 

A mixed pathophysiological model for LARS:

Reservoir function of the neorectum

Standard rectal cancer treatment today is by total mesorectal excision with sphincter preservation if possible. Some patients require neoadjuvant therapy to downstage a potentially non-resectable cancer or to minimize the risk of local recurrence in resectable cancers. The surgical resection is thought to be the primary cause of LARS due to loss of reservoir function. Several efforts to restore reservoir function have been made in the form of coloplasty, side-to-end anastomosis and J-pouch. The main benefit of these modifications are in the first 1-2 years, but seems to diminish thereafter (35). Some studies have also shown that oncologically safe Partial Mesorectal Excision (PME) performs better from a functional standpoint than a Total Mesorectal Excision (TME) (36, 37) (Figure 1). Anal sphincter manometry has failed to show any significant change in anal sphincter function related to surgical or oncological treatment. Poor preoperative anal sphincter function is a strong predictor of LARS and should be taken into consideration at initial treatment planning.

Afferent sensory loss

The length of the rectal remnant retained as measured on MR scan correlates with a significantly better functional outcome (38). This beneficial effect is lost in irradiated patients. Both RCT’s and epidemiological studies show a greatly increased risk of severe LARS using neoadjuvant therapy (33, 36, 39, 40). This suggests that rectal function is highly dependent on afferent sensory input from the remaining mucosa distal to the anastomosis or from the pelvic sidewalls. Therefore, it is of importance to select patient who will actually benefit from radiotherapy.

The negative impact of a diverting stoma

A temporary stoma after TME is widely practiced in order to avoid the consequences of an anastomotic leak. A recent revisit of a randomised study comparing TME surgery with or without a diverting stoma showed that patients with a diverting stoma had an increased risk of developing LARS five years after surgery (41). The precise aetiology is not known, but could be related to diversion colitis, or to changes in epithelial function of the terminal ileum, causing bile acid malabsorption, small bowel bacterial overgrowth or bacterial re-colonisation of the colon after the stoma reversal.

Autonomic denervation

Food intake strongly stimulates faecal urgency in LARS patients and there is an increased gastrocolic reflex (42). This is probably caused by autonomic denervation of the neorectum although the bowel has its own neural network able to work independently of extrinsic sympathetic or parasympathetic innervation. Integrated autonomic function relies on extrinsic innervation. In general, the sympathetic nerves inhibit peristalsis, whereas the parasympathetic nerves promote peristalsis. After rectal resection the bowel proximal to the anastomosis is without parasympathetic and to some extent without sympathetic extrinsic innervation due to central vessel ligation causing damage to the sympathectic supply from the superior hypogastric plexus in the front of the aorta.

Chemotherapy and pelvic radiation disease

Chemotherapy-induced GI symptoms is related to small bowel bacterial overgrowth, bile acid malabsorption or pancreatic insufficiency, causing diarrhoea, flatulence, bloating, pain or constipation (43). Although modern radiotherapy aims to diminish the area receiving radiation, scatter still occurs to adjacent structures, such as to the small bowel, or to pelvic organs. In the longer term, radiation causes ischaemic and fibrotic changes as well as initial mucosal inflammation. Cell death results in impairment of GI physiological function. Chronic GI symptoms are caused by a variety of processes so that symptoms alone are unreliable at predicting the underlying cause (44). Further evaluation should include: vitamin B12, thyroid function , coeliac screen, Selenium homocholic acid taurine (Se HCAT) scan, glucose hydrogen breath test and both upper and lower GI endoscopy. Algorithm based management programs has proven effective in managing post resection symptoms which can be used by nurse specialists (45).

Unknown functional outcome following new treatment modalities for rectal cancer

Some small early cancers can be curatively treated by local excision alone. New options for curative chemoradiotherapy using a watch and wait policy or local excision after complete or partial response may avoid resectional therapy. The main argument for these new developments is a better functional outcome without oncological compromise. However the functional outcome of these procedures remains to be evaluated.


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