Low Anterior Resection Syndrome, Role of SNM?

Abstract

Low anterior resection syndrome (LARS) includes all bowel dysfunctions after rectal cancer surgery, causing significant damage to survivors' quality of life. Among different therapeutical approaches, sacral neuromodulation (SNM) has become an interesting technique to palliate LARS symptoms. This article highlights the pathophysiology of LARS, describing the most important aspects of SNM in this scenario.

Colorectal cancer is one of the most common malignancies reported worldwide. Approximately 30% of these tumors develop in the rectum, ¹ with an increase of incidence in younger adults. ² Parallelly, rectal cancer surgery has radically evolved over the past decades. Development of minimally invasive techniques and consistent use of total mesorectal excision (TME) together with multimodal oncological treatment have led to higher rates of anal sphincters preservation and cancer survivors. ^{3 4} In turn, survivor's lifestyle does not come back to normal after rectal cancer treatment due to the impairment in bowel, urinary, and sexual function, which are very limiting and difficult to manage. These dysfunctions are known as low anterior resection syndrome (LARS), which includes a wide constellation of symptoms such as fecal incontinence and/or urgency, stool clustering, and fragmentation. LARS translates into impairment of patients' daily activities that end up in “toilet-dependence” and deterioration of their quality of life, even in the long term. ⁵ Currently, after a consensus between healthcare professionals and the patient, diagnosis of LARS has pivoted to the presence of at least one bowel dysfunction symptom provoking at least one consequence in patient's lifestyle. ⁶

The pathophysiology of LARS is still unknown and multiple risk factors have been described. Among them are the direct lesion of the anal sphincters during the anastomotic procedure, the damage of the nerves involved in the defecation with anal–rectal inhibitory reflex annulment, the decrease of the distensibility and denervation of colonic plasty, the use of preoperative radiotherapy which might reduce the elasticity of the tissues, and the presence of a diverting ileostomy which can duplicate the risk of LARS. ^{7 8 9} The ultimate cause of LARS is the lack of rectum, and amputation of this organ limits a specific treatment.

Patients with LARS might suffer from different digestive patterns. These include an incontinence pattern in which patients describe a deficit in fecal storage, and a frequency pattern in which patients revisit the toilet frequently and present with fecal fragmentation. ¹⁰ However, some patients might have a mixed pattern. Recent studies with colonic manometry have showed different impairments in normal motility. Significant reduction in the sigmoid cyclic motor pattern, which acts as a natural brake to colonic peristalsis, has been observed in patients with LARS compared with healthy adults. ^{11 12} Also, a higher occurrence of cyclic short antegrade motor patterns and less high amplitude propagating contractions from the proximal colon might be responsible for these different clinical patterns. ¹³

Due to the devasting effects of LARS on survivors' quality of life, patients must be thoroughly informed of these dysfunctions before surgery, and surgeons must also identify those affected after surgery. As with any other functional pelvic disorder, the first therapeutic approach for LARS should be conservative. Regulation of fecal consistency and fecal bulking through high fiber intake and the use of anti-diarrheal agents such as loperamide or cholestyramine can be useful for LARS patients. It is recommended to instruct patients at an early stage after reconstruction to achieve a self-management control, and changing their dietary or medication habits according to their symptoms. ¹⁴

Pelvic floor rehabilitation (PFR) is aimed at restoring muscular strength and enhancing pelvic floor contractions to ensure a better defecation coordination and has shown good results in LARS patients, especially if initiated with the early symptoms onset after transit reconstruction. ¹⁵ Tibial nerve stimulation has also shown to improve fecal incontinence in LARS patients. ¹⁶ The use of transanal irrigation (TAI) provides a mechanical flush of the colon with warm water to remove feces with defecation-free days, which is gaining popularity in the non-conservative management of LARS, with very positive results. ¹⁷ However, both PRF and TAI require patient's compliance and motivation, access to specialized centers for adequate treatment and instruction, and time availability.

Sacral neuromodulation (SNM) has emerged over the last decades as a promising treatment for patients suffering from pelvic floor disorders such as fecal and urinary incontinence, having proved to be a safe and effective therapy even in the long term. ¹⁸ SNM is a two-stage procedure consisting of a test phase with a lead and a subsequent implantation of a generator in those patients in whom a good clinical response is observed. The technique's minimal invasiveness, low risk and low comorbidity, the possibility of performing a diagnostic/therapeutic test, and development of new MRI compatible technology have contributed to widening of indications in patients with pelvic floor disorders. ¹⁹ This is also the case with LARS. The first studies reporting the use of SNM after rectal resection following the optimal results described in the treatment of fecal incontinence with native rectum is not new and were published before surgeons even defined LARS in its current form, or its risk factors. ^{20 21} However, only short case series and retrospective or prospective studies have been published since then, not without an increasing interest among the colorectal surgery community. In fact, there are four systematic reviews published to date. The most recent systematic review and meta-analysis included 18 studies with 164 patients with a final clinical success rate of 77% after permanent implant, reporting improvement in incontinent episodes, Wexner score, and quality of life. ²² However, the small sample of patients, lack of control groups, nature of methodology, and high heterogeneity of the studies included in all the reviews limited definitive conclusions.

A recent randomized, crossover, multicentric trial to assess the efficacy of SNM in major LARS ²³ has shown favorable results with an implantation rate of 76% that is in line with previously published systematic reviews. Patients with active modulation during the crossover phase and after it showed improvement in LARS, St Mark's continence score, and quality of life score. The number of urgency/incontinence and clustering episodes also improved with SNM.

The mechanism of action through which SNM might work in LARS is still unclear, as it is in patients with fecal incontinence and no rectal resection history. As stated before, new investigations in colonic motility performed with high-resolution manometry have shown changes in different colonic movement patterns which might be responsible for LARS symptoms and patterns. One of them is the sigmoid cyclic motor pattern which acts as a natural brake to stop feces entering the rectum. SNM could act by upregulating sequences of propagation in the neorectum and remnant colon, combined with cyclic motor pattern initialization, thereby normalizing distal colonic motility and delaying the flow of feces into the rectum. In addition, neorectal sensitivity can also improve with SNM, contributing to better function and amelioration of other symptoms (e.g., fragmentation). ^{24 25}

Patients must be guided and counseled thoroughly to understand the complexity of LARS and the rationale for using SNM, adjusting realistic expectations of potential benefits of the therapy. The ideal candidates who might benefit from SNM have not been clearly identified yet. After the results published in different systematic reviews and the SANLARS trial, which showed positive effects of SNM in terms of improvement in continence scores, daily fecal urgency episodes, sensation of complete bowel emptying, and better stool/gas discrimination, it is plausible to consider patients with a refractory incontinence phenotype. ²³ However, patients with a fragmentation or mixed symptom pattern might also benefit from this therapy and should not be excluded.

Extra digestive symptoms are common and expected after rectal cancer resection due to the proximity of pelvic organs and nerve and muscle damage caused by surgical procedures. Many patients refer to urinary and sexual dysfunctions that are sometimes eclipsed by bowel symptoms. Little evidence has been reported on the management of extra digestive symptoms in LARS patients, but since SNM is a multidimensional approach to pelvic disorders, it might be useful in palliating other non-intestinal symptoms in LARS, but this needs elucidation in future studies.

Even though there are no specific contraindications for SNM in LARS patients (except the general ones described for any other patient), particular attention should be paid in patients who had had an anastomotic failure or sinus. According to the data from the SANLARS trial, 40% of patients who did not respond to initial evaluation had reported anastomotic leakage. ²³ This could be probably related to fibrosis-induced changes in the pelvis that might impede modulation inputs to provide clinically relevant changes. It is therefore reasonable to have realistic expectations from SNM in this scenario.

SNM implantation in LARS patients should be performed following the recommended guidelines as in any other indication. ²⁶ Due to fibrotic changes in the pelvis induced by surgical dissection and radiotherapy, the surgeon might encounter some placement difficulties during needle, dilator, and lead implantation into the sacrum. Also, radiological markings can be hard to distinguish due to the changes in the pelvis anatomy. Therefore, advanced testing with tined lead should be preferred to percutaneous nerve evaluation (PNE) considering these potential technical difficulties and the fact that LARS patients might need prolonged test time (up to 3 weeks) to detect clinical improvement. There is no evidence regarding foramina selection in LARS patients (S3 versus S4), but it is appropriate that the lead should be implanted in S3 to recruit more nerve fibers and to include a potential approach to fecal and urinary dysfunction (not reached by S4 stimulation). Careful S3 motor responses should be checked to avoid any kind of leg twist (S2 response) that might produce undesirable effects after implantation. The best motor and sensitive response in these patients might be achieved when at least three out of the four poles are left very close or within the sacral bone. This might be because the nerve path might be damaged due to the fibrotic changes previously mentioned.

Timing to introduce SNM as a therapeutical treatment has not been established. As stated before, the first approach should be conservative immediately after transit reconstruction. It is sensible to establish a noninvasive approach as a second step if symptoms persist, as previously recommended. ²⁷ Therefore, it is plausible to consider SNM for refractory LARS after 6 months of unsuccessful conservative treatment. Patients with a clear incontinence pattern and the presence of extra digestive symptoms could be ideal candidates for an early SNM implantation, but further studies are needed in this direction. Once the patient is implanted, strict follow-up is mandatory to detect relapses in symptoms and provide reprogramming sessions to restore clinical efficacy when needed.

The role of SNM in LARS patients is gaining momentum due to the safety, minimal invasiveness, and promising results this treatment has reported so far. Careful selection of patient and implantation technique along with a comprehensive discussion with patients providing realistic expectations is advised to guarantee the best results.