Low anterior resection syndrome (LARS)

INTRODUCTION — Surgery is the only curative therapy for rectal cancer. Transabdominal surgery can be performed with either sphincter-sparing techniques (ie, anterior resection) or an abdominal perineal resection. Historically, abdominoperineal resection was the gold standard for treating low-lying rectal cancers. With the advent of better surgical techniques and equipment (eg, staplers) as well as neoadjuvant therapy, abdominoperineal resection has been gradually replaced by sphincter-sparing procedures. For patients in whom a negative distal margin can be achieved, sphincter-sparing procedures are preferred because they maintain bowel continence and avoid a permanent colostomy. In contemporary practices, sphincter-sparing procedures are feasible in up to 80 percent of patients requiring surgery for rectal cancer.

However, functional disturbances constitute a major problem for many surviving rectal cancer patients following a sphincter-sparing procedure, with symptoms ranging from daily episodes of incontinence to obstructed defecation and constipation. Although such symptoms have an immense impact on the patient's quality of life, there is presently no specific treatment. Instead, management is empirical and symptom based, using existing therapies for fecal incontinence, fecal urgency, and rectal evacuatory disorders.

In this topic, we discuss the clinical manifestations, diagnosis, and treatment of bowel symptoms that develop following sphincter-sparing resections of the rectum. Such symptoms have been collectively referred to as low anterior resection syndrome (LARS). The techniques of sphincter-sparing resection and the treatment of fecal incontinence, urgency, or other rectal evacuatory disorders of the gastrointestinal tract not necessarily related to surgery are discussed separately. (See "Surgical treatment of rectal cancer" and "Fecal incontinence in adults: Management" and "Management of chronic constipation in adults".)

DEFINITION — LARS is defined by at least one of the following symptoms resulting in at least one of the following consequences that occur after a sphincter-sparing resection (ie, anterior resection) of the rectum [1]:

Symptoms:

●Variable, unpredictable bowel function

●Altered stool consistency

●Increased stool frequency

●Repeated painful stools

●Emptying difficulties

●Urgency

●Incontinence

●Soiling

Consequences:

●Toilet dependence

●Preoccupation with bowel function

●Dissatisfaction with bowels

●Strategies and compromises

●Impact on mental and emotional wellbeing

●Impact on social and daily activities

●Relationships and intimacy

●Roles, commitments, and responsibilities

EPIDEMIOLOGY AND RISK FACTORS — According to a 2021 systematic review and meta-analysis of 50 studies, the pooled incidence of major LARS is 44 percent (95% CI 40 to 48 percent) [2]. About 50 percent of patients still report symptoms more than 10 years after surgery [3,4]. For individual patients, symptoms vary in type, severity, and duration as a reflection of different underlying etiologies.

Potential risk factors for LARS include [2]:

●Long-course neoadjuvant radiotherapy (odds ratio [OR] 2.89, 95% CI 2.06–4.05) [5-7]

●Total mesorectal excision (TME) (OR 2.13, 95% CI 1.49–3.04)

●Anastomotic leak (OR 1.98, 95% CI 1.34–2.93)

●Diverting stoma (OR 1.89, 95% CI 1.58–2.27)

No significant difference in postoperative anorectal dysfunction has been observed between open and laparoscopic TME [8]. Pouch reconstruction was not found to be significantly beneficial to anorectal functions in long term.

Among these potential risk factors, pelvic radiotherapy is consistently associated with LARS, regardless of the timing of administration (neoadjuvant versus adjuvant) [5,6]. By contrast, neoadjuvant chemotherapy, whether administered alone or added to chemoradiation therapy, did not seem to impair bowel function [7].

The presence of defunctioning stoma seems to have a negative impact on functional bowel activity after low rectal resection, in particular for delayed closure (>90 days) and for ileostomy. This should be considered when the type of stoma (ileostomy versus colostomy) is selected for each patient [9].

PATHOPHYSIOLOGY — Symptoms of LARS are usually caused by a combination of colonic dysmotility, neorectal reservoir dysfunction, and anal sphincter dysfunction.

Colonic dysmotility — LARS can be caused by increased proximal colonic motility coupled with a lack of distal inhibition in patients who undergo sphincter-sparing resections.

There is evidence that denervation of the remnant sigmoid colon [10] or left colon [11] by operative maneuvers (eg, ligation of a vascular pedicle) can result in a significant increase in motility. As a result, patients with LARS have a shorter colonic transit time [12,13] and a greater increase in neorectal pressure after a meal compared with patients who do not have LARS [14].

Removal of the rectum and in particular the rectosigmoid junction eliminates the physiologic distal control center for the regulation of bowel transit, leaving the bowel activities without a "brake." This lack of distal negative feedback signals to oppose increased proximal colonic motility further exacerbates the symptoms of LARS.

Neorectal reservoir dysfunction — Two aspects of neorectal reservoir dysfunction, denervation and reduction in functional capacity, both contribute to LARS symptoms.

The remnant rectum or neorectum may be denervated by surgical dissection or pelvic radiotherapy. A denervated neorectum is hyposensitive to mechanical and thermal stimuli due to impaired afferent nerve function [15] and is thus susceptible to causing LARS symptoms. There is evidence that the risk of LARS is greater after total as opposed to partial mesorectal excision and after neoadjuvant therapy.

Besides denervation, the neorectal function may also be compromised by a reduction in its capacity and compliance. After rectal surgery, smaller volumes of fecal material may be sufficient to induce contraction or spasm of the neorectum, which can cause symptoms such as urgency, soiling, or multiple evacuations. Although such symptoms may be obviated in part by the construction of a neorectal reservoir (eg, colonic J-pouch), the benefit lasts for fewer than 18 months [16], suggesting that reconstructive techniques play only a transient role in determining functional outcomes after sphincter-sparing surgery. (See "Radical resection of rectal cancer", section on 'Anastomosis'.)

Anal sphincter dysfunction — Anal sphincter dysfunction can be a complication of rectal surgery or pelvic radiotherapy. In one study, up to 18 percent of patients who underwent stapled low anterior resection had evidence of long-term internal anal sphincter injury [17]. Intersphincteric resections performed to ensure an adequate distal margin can further alter sphincter functions. Anal sphincter dysfunction can contribute to LARS symptoms such as fecal incontinence or urgency.

PREVENTION — Since all patients who undergo a sphincter-sparing rectal resection are at risk of developing LARS, postoperative efforts should be made to prevent LARS. Upon hospital discharge, all patients should be instructed to perform home Kegel exercises as a form of pelvic floor muscle training.

Additionally, patients who receive a protective stoma as a part of their low anterior resection may be at increased risk of developing LARS. In a follow-up study 12 years after a randomized trial, patients who underwent low anterior resection with a protective stoma reported increased incontinence for flatus and liquid stools and worse overall LARS score compared with patients who underwent low anterior resection without a protective stoma [18]. Thus, patients who have a protective stoma that is not expected to close within one to two months should also receive daily or two- to three-times-per-week enemas or anterograde colonic irrigation via the stoma. (See 'Colonic irrigation' below.)

CLINICAL MANIFESTATIONS — Common symptoms of LARS include:

●Fecal urgency

●Fecal incontinence

●Increased frequency of bowel movements

●Fragmentation and clustering of bowel movements

●Emptying difficulties or incomplete evacuation

●Increased intestinal gas

●Diarrhea

●Constipation

●Change in stool consistency

DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS — LARS should be suspected in patients who develop one or more bowel symptoms after undergoing a sphincter-sparing resection of the rectum. The diagnosis is confirmed when the symptom(s) persist beyond one month after surgery and an evaluation fails to elucidate an alternative etiology.

Although bowel symptoms are common after rectal surgery, not all should be attributed to LARS. Patients with the following complaints require an evaluation to exclude alternative diagnoses:

●Patients who have sepsis or peritonitis may have an anastomotic failure. Abdominopelvic computed tomography (CT) or barium enema can be used to exclude anastomotic complications. (See "Management of anastomotic complications of colorectal surgery".)

●Patients who have bloody diarrhea may have inflammatory bowel disease, toxic colitis, ischemic colitis, or chemotherapy-induced colitis. Endoscopic examination of the lower gastrointestinal tract with colonoscopy, sigmoidoscopy, proctoscopy, or anoscopy could reveal mucosal alterations or enable tissue biopsy to confirm the diagnosis. (See "Clinical manifestations, diagnosis, and prognosis of ulcerative colitis in adults" and "Clinical manifestations, diagnosis, and prognosis of Crohn disease in adults" and "Toxic megacolon" and "Colonic ischemia" and "Chemotherapy-associated diarrhea, constipation and intestinal perforation: pathogenesis, risk factors, and clinical presentation".)

●Patients who have tissue prolapse from the rectum may have rectal/neorectal prolapse or other pelvic organ prolapse such as pelvic/perineal hernia or enterocele. Barium or magnetic resonance defecography can detect enteroceles, rectoceles, or rectal prolapse in addition to evaluating the length of the anal sphincter, anorectal angle, and pelvic descent. (See "Overview of rectal procidentia (rectal prolapse)", section on 'Clinical features' and "Overview of rectal procidentia (rectal prolapse)", section on 'Diagnosis' and "Management of perineal complications following an abdominal perineal resection", section on 'Perineal hernia' and "Pelvic organ prolapse in females: Epidemiology, risk factors, clinical manifestations, and management", section on 'Clinical manifestations' and "Etiology and evaluation of chronic constipation in adults".)

●Patients who have obstructive symptoms, such as nausea, vomiting, or obstipation, may have postoperative adhesions. Abdominopelvic CT is the imaging modality of choice to diagnose a bowel obstruction. (See "Postoperative peritoneal adhesions in adults and their prevention", section on 'Clinical presentations and diagnosis'.)

●Patients who have fecal incontinence should undergo endoscopic ultrasound examination of the anal sphincter complex to rule out a sphincter injury. Additionally, neurophysiologic tests (eg, electromyography [EMG]) can be performed in patients with clinically suspected neurogenic sphincter weakness, particularly if there are features suggestive of sacral root involvement. (See "Endorectal endoscopic ultrasound (EUS) in the evaluation of fecal incontinence" and "Fecal incontinence in adults: Etiology and evaluation", section on 'Other'.)

●Patients whose main symptoms are excessive gas, flatulence, or abdominal bloating may have small intestinal bacterial overgrowth (SIBO). SIBO can be diagnosed by a lactose breath test. (See "Approach to the adult patient with suspected malabsorption", section on 'Small intestinal bacterial overgrowth'.)

●Patients suspected of having recurrent rectal cancer based on postsurgical surveillance should undergo colonoscopy to confirm the diagnosis. (See "Post-treatment surveillance after colorectal cancer treatment" and "Treatment of locally recurrent rectal adenocarcinoma", section on 'Mode of presentation'.)

●Patients whose bowel symptoms predate sphincter-sparing surgery may have irritable bowel syndrome. However, LARS can be difficult to distinguish from diarrhea-predominant irritable bowel syndrome (IBS-D) because the symptoms overlap and both are diagnoses of exclusion. (See "Clinical manifestations and diagnosis of irritable bowel syndrome in adults", section on 'Diarrhea'.)

DIAGNOSTIC EVALUATION — Evaluation of LARS begins with a history and physical examination. Patient questionnaires, such as the Low Anterior Resection Syndrome Score or the Memorial Sloan Kettering Cancer Center Bowel Function Instrument, should be used to stratify patients based upon the severity of their symptoms and to guide therapy. Although they are not diagnostic, adjunctive tests, such as manometry, imaging, or endoscopy, may be required to elucidate etiology, exclude alternative diagnosis, or guide treatment. (See 'Diagnosis and differential diagnosis' above.)

Patient questionnaires — Two patient questionnaires have been validated and widely used for assessing patients with LARS. Scores generated by such instruments are not used to diagnose LARS but to quantify the severity of the illness and to monitor the effectiveness of therapy.

●The Low Anterior Resection Syndrome Score (LARS score; 2012) is a validated questionnaire for assessing bowel function after sphincter-sparing surgery for rectal cancer [19]. Only five questions are asked by this questionnaire: incontinence for flatus, incontinence for liquid stool, fecal frequency (number of bowel movements per day), clustering of (less than an hour between) bowel movements, and urgency (calculator 1). Based upon their scores, patients are stratified into minor or major LARS. Major LARS, defined by a LARS score of ≥30, is typically associated with seriously compromised quality of life and therefore requires intensive or invasive treatment. Minor LARS (score <30) can be treated medically for individual symptoms. (See 'Treatment' below.)

The LARS score is widely used in clinical practice owing to its conciseness and ease of scoring. Its severity categories are also clinically meaningful and correlate with patients' quality of life. The LARS score has been translated from Danish into many other languages (English, Dutch, Swedish, Spanish, Chinese, German, and Lithuanian) and has been validated in those respective countries.

However, the LARS score may be insensitive to evacuatory dysfunction and overestimate the impact on quality of life for some patients [20]. There is also a high rate of LARS-like symptoms in the general population. As an example, a study in Denmark reported that 19 percent of females and 10 percent of males from the general population had a LARS score ≥30, corresponding to the category of "major LARS," and the median score for females and males surveilled was 16 (7 to 26) and 11 (4 to 22), respectively [21]. This reflects the high sensitivity but low specificity of the LARS score.

●The Memorial Sloan Kettering Cancer Center Bowel Function Instrument (MSKCC BFI; 2005) was the first questionnaire specifically validated for evaluating bowel function after sphincter-sparing surgery for rectal cancer [22]. It consists of 18 questions on a variety of LARS-related issues. Its complexity in scoring (which involves recoding, three subscale scores, a global score, and a total score) limits its use in clinical practice.

Anorectal/colonic manometry — Anorectal/colonic manometry is not required to diagnose LARS but can be helpful in monitoring patient response to treatment, especially for major LARS. (See 'Neurostimulation' below.)

Resting and squeeze sphincter pressures in LARS are typically normal or reduced. In some patients, however, the sphincter pressure may be increased as an involuntary response to fecal incontinence or abnormal straining maneuvers in a dyssynergic pattern.

In LARS, both the capacity and compliance of the neorectum are typically reduced compared with the presurgical baseline. The neorectal sensibility can be normal, reduced, or increased depending upon the anastomotic height, any inflammation or anastomotic complication in the neorectum, or previous pelvic radiotherapy.

Colonic manometry in LARS often reveals a reduction in segmental contractile activities and an increase in high-amplitude propagated contractions. The latter is correlated with colonic mass movements.

TREATMENT — At one month after the initial surgery without a stoma or after the protective stoma is closed, patients who have persistent bowel symptoms are diagnosed with LARS and evaluated with one of the patient questionnaires, such as the LARS score. Further treatment options are dependent upon the LARS score.

LARS can be treated with medications, transanal irrigation, pelvic floor rehabilitation, neurostimulation, or surgery [23]. The choice of treatment(s) is based upon the variety, severity, and duration of symptoms (algorithm 1).

For most patients with LARS, nonoperative therapies, including pelvic floor rehabilitation and transanal irrigation, and minimally invasive procedures such as sacral nerve stimulation are the mainstay of treatment. A multimodal approach generally works better than any single therapy. Given the lack of high-quality evidence in this field, recommendations are generally based upon retrospective studies or extrapolated from studies on nonsurgical patients with similar gastrointestinal disorders (eg, irritable bowel syndrome) [24].

Counselling and follow-up of patients with LARS should be organized proactively and include a clinical nurse specialist [25].

Minor LARS — Patients who have a LARS score <30 have minor LARS. Patients with minor LARS typically have preserved quality of life, and most can be treated medically for one or more specific symptom(s), including (algorithm 1):

Diarrhea — Loperamide is most commonly used to treat diarrhea associated with LARS. Although loperamide has not been specifically studied in LARS, its use is supported by its efficacy in treating two similar disorders, diarrhea-predominant irritable bowel syndrome (IBS-D) and bowel dysfunction after restorative proctocolectomy (see "Treatment of irritable bowel syndrome in adults" and "Restorative proctocolectomy with ileal pouch-anal anastomosis: Laparoscopic approach", section on 'Functional results'):

●Loperamide is the only antidiarrheal agent that has been evaluated in randomized trials in patients with IBS-D [26]. In IBS-D patients, loperamide was more effective than placebo in reducing the number of bowel movements and improving stool consistency.

●In patients who have undergone a restorative proctocolectomy with construction of an ileoanal pouch, loperamide significantly lowered stool frequency and modified some aspects of pouch contraction in one study [27] and improved anal sphincter function and continence in another [28].

In patients with persistent diarrhea despite antidiarrheals, bile acid sequestrants can be used. Bile acid malabsorption can occur after colorectal surgery and cause symptoms such as diarrhea, fecal urgency, frequency, or incontinence. Having been successfully used to treat bile acid malabsorption after pelvic radiation [29] and from IBS-D [30], bile acid sequestrants (eg, colesevelam) are being investigated as potential treatments for LARS. (See "Treatment of irritable bowel syndrome in adults", section on 'Bile acid sequestrants'.)

Postprandial urgency or incontinence — Some patients with LARS have an exaggerated postprandial response in the neorectum of urgency and/or incontinence. For such patients, one of the serotonin- (5-hydroxytryptamine)-3 receptor (5-HT₃) antagonists, in particular ramosetron, may be used to control their symptoms.

In one trial, 100 male patients with LARS one month after rectal cancer surgery or ileostomy reversal were treated with 5 mcg of ramosetron hydrochloride daily or routine management [31]. After one month, fewer patients who received ramosetron (58 versus 82 percent) still had major LARS. There were no major adverse effects or difference in minor adverse effects.

Other 5-HT₃ antagonists (eg, alosetron or cilansetron) have also been used to treat exaggerated intestinal/colonic hypermotility in IBS-D patients but have not been studied in LARS patients. (See "Treatment of irritable bowel syndrome in adults", section on '5-hydroxytryptamine (serotonin) 3 receptor antagonists'.)

Gas and bloating — Patients whose main symptoms are excessive gas, flatulence, or abdominal bloating can be treated with antibiotics such as rifaximin or neomycin. Symptoms related to excessive intestinal gas production, including flatulence and abdominal bloating, can be caused by small intestinal bacterial overgrowth (SIBO). SIBO occurs with expansion of gut microbes from the colon to the small intestine, where the microbes produce excessive intestinal gas by abnormal fermentation of food [32]. Antibiotics, such as neomycin and rifaximin, can help reduce or eliminate SIBO. (See "Small intestinal bacterial overgrowth: Management".)

Fecal soilage — In patients whose main symptoms are soiling or mild passive fecal incontinence, intra-anal injection of bulking agents can be used as part of a multimodal approach. Its value as a stand-alone therapy, however, is limited. (See "Fecal incontinence in adults: Management", section on 'Injectable anal bulking agents'.)

Ineffective medical treatments — First-line conservative measures, such as dietary restrictions, fiber, constipating agents, or enemas, typically do not have good control of LARS symptoms; their impact on patient satisfaction and quality of life is doubtful and not supported by evidence. The following medications or supplements have been tried and found ineffective against LARS symptoms:

●Probiotics have a limited role in the prevention or treatment of LARS. In one study, the use of a probiotic preparation, VSL#3, did not alter the postoperative bowel function of patients undergoing loop ileostomy reversal after a sphincter-sparing resection [33].

●Fiber intake can improve stool consistency by absorbing water but not any other bowel symptoms. It is often poorly tolerated in LARS patients due to bloating and abdominal pain.

●There is no evidence supporting the use of steroids or nonsteroidal anti-inflammatory drugs in the treatment of LARS.

Major LARS — Patients who have a LARS score ≥30 have major LARS. Major LARS has a significant negative impact on patients' quality of life. Thus, patients with major LARS typically require multimodal therapy rather than medical treatment for individual symptoms as described above (algorithm 1).

Multimodal therapy for LARS consists of transanal irrigation (TAI) daily or three to four times per week plus pelvic floor rehabilitation (including biofeedback, pelvic floor muscle training, balloon training, and electrostimulation). Patients who have major LARS should receive such treatment for six months to one year before they are reevaluated with the LARS score. Patients who no longer have major LARS on repeat evaluation can be treated medically for any symptoms that persist. (See 'Minor LARS' above.)

Patients who continue to have major LARS after one year of multimodal therapy should be treated with neurostimulation (eg, sacral nerve stimulation). Patients who do not respond to neurostimulation and continue to have major LARS and severely compromised quality of life should be offered a diverting stoma in another year (ie, after a total of two years from the start of multimodal therapy).

Colonic irrigation — TAI is a simple, safe, effective, and inexpensive treatment for LARS patients who primarily have symptoms of fecal incontinence or frequency [34,35]. TAI is typically used in conjunction with pelvic floor rehabilitation in those with major LARS. (See "Ileostomy or colostomy care and complications", section on 'Colon irrigation'.)

Low-volume TAI simply achieves the effect of a mechanical washout. High-volume (>250 mL) irrigation generates functional colonic responses, such as colonic mass movements, which improves colonic transit time and fecal continence when administered regularly. Patients who have low rectal volume, low maximal rectal capacity, and/or low anal squeeze pressure respond most favorably to TAI.

TAI for LARS is typically performed transanally in a retrograde fashion. Patients are trained by a stoma nurse to perform TAI with one of the commercially available systems (eg, the Peristeen anal irrigation system) daily or three to four times per week. During each treatment, 500 to 1500 mL of water was instilled into the colon [34].

In a trial of 45 patients with major LARS following rectal cancer surgery and total mesorectal excision, TAI resulted in lower LARS score (23 versus 32) and improved quality of life compared with conservative management at one year [36].

In one study of 14 patients with LARS, the number of bowel movements during the day and at night both decreased (8 to 1 and 3 to 0, respectively), and quality of life improved after regular TAI for an average of 29 months [34]. In another study of 33 patients, the median LARS score fell from 35.1 (range 30 to 42) to 12.2 (range 0 to 21) after six months of TAI, and quality of life improved in several domains as well [37].

The risk of bowel perforation associated with TAI has been estimated to be about 2 per million procedures [38]. Risk factors include suboptimal patient evaluation, wrong indications, lack of training, and poor patient compliance.

One center in France treated 25 patients for major LARS after total mesorectal excision with anterograde enema (one liter of tap water) administered via a percutaneous endoscopic cecostomy (PEC) [39]. LARS score significantly improved after treatment (33 versus 4). At the end of the follow-up (median 8 months, range 1 to 33 months), the PEC catheter was removed from four patients (16 percent), indicating treatment failure; three of the four patients underwent a permanent colostomy.

Pelvic floor rehabilitation — LARS patients who present with fecal incontinence or frequency can also benefit from pelvic floor rehabilitation (PFR). PFR is typically used in conjunction with TAI in those with major LARS.

PFR refers to a collection of rehabilitative techniques that includes biofeedback, pelvic floor muscle training, electrostimulation, and volumetric/rectal balloon training. Specific techniques are selected according to the individual needs of each patient, although a combination of techniques has been shown to significantly improve outcomes compared with individual techniques alone [40].

Both pelvic floor muscle training [41-43] and biofeedback [44] have been associated with improvements in bowel function and health-related quality of life in patients with LARS:

●In one small trial of about 100 patients, those who performed pelvic floor muscle training regularly starting at one month after sphincter-sparing resection or ostomy closure reported greater improvement in LARS category than controls at four and six months, but not 12 months [45].

●In another study of patients after sphincter-sparing surgery, significant improvements were observed after biofeedback therapy in fecal incontinence score, number of bowel movements, and anorectal manometry data (maximum resting pressure, maximum squeeze pressure, and rectal capacity) [44].

●In a third study, patients with LARS benefited equally from PFR regardless of whether they received adjuvant pelvic radiotherapy [46].

However, the available studies on PFR in LARS are generally of low quality due to the heterogeneity in the PFR protocols and fecal incontinence scoring systems used. A 2015 systematic review concluded that the majority of studies reported significant improvements in stool frequency, incontinence episodes, severity of fecal incontinence, and quality of life after pelvic floor muscle training, but a meta-analysis was not possible due to the heterogeneity in study designs. High-quality data are required to validate the efficacy of PFR used for LARS.

The same PFR techniques are used to treat patients with pelvic organ prolapse, urinary incontinence, or pelvic pain syndrome and are further discussed in other topics. (See "Myofascial pelvic pain syndrome in females: Pelvic floor physical therapy for management" and "Pelvic organ prolapse in females: Epidemiology, risk factors, clinical manifestations, and management", section on 'Pelvic floor muscle exercises' and "Female urinary incontinence: Treatment", section on 'Pelvic floor muscle (Kegel) exercises'.)

Neurostimulation — Patients who continue to have major LARS after one year of multimodal therapy should be evaluated for neurostimulation (eg, sacral nerve stimulation [SNS]). SNS has been shown to improve fecal incontinence and the ability to defer defecation in patients with normal or impaired sphincters [47].

SNS was initially thought to directly act upon anal sphincter muscles through peripheral motor stimulation to increase resting and squeeze pressures but is now believed to exert more influence on anorectal functions at a pelvic afferent or central level. Additionally, SNS has also been shown to decrease anterograde while increasing retrograde colonic motor activities [48] and to impair postprandial changes in rectal motility [49]. The latter two mechanisms are most relevant for LARS patients.

SNS involves placement of an electrode into the sacral foramen to provide low-grade electrical stimulation to the sacral nerve. Patients who respond to a two-week trial with a temporary electrode then undergo placement of a permanent electrode connected to a generator embedded subcutaneously.

SNS has been studied in patients with LARS [50-57]; approximately 72 percent of patients who underwent temporary stimulation went on to receive a permanent stimulator (table 1). After a follow-up of 12 to 32 months, most patients achieved good functional results with improvements in incontinence episodes, the ability to defer bowel movement, fragmentation or urgency in defecation, and quality of life. Manometric results varied and did not always correlate with functional outcomes.

Similar conclusions were reached by a 2015 systematic review, which included 43 patients with a median follow-up of 15 months [58]. In that study, 79 percent of patients who underwent temporary stimulation received a permanent stimulator, 94 percent of whom experienced improvement of symptoms. However, all the studies that have been conducted to date are small, retrospective, and heterogenous; high-quality evidence is required to validate SNS as a standard treatment for LARS.

Other techniques of neurostimulation (eg, posterior tibial nerve stimulation [PTNS] and electroacupuncture) are being investigated as potential treatments for LARS but are not yet available for widespread clinical use. In a trial of 46 patients with LARS, LARS scores were reduced from 36.4 (standard deviation 3.9) to 30.7 (11.5) at 12 months, and fecal incontinence scores were reduced from 15.4 (5.2) to 12.5 (6.4) after PTNS [59]. The LARS scores were also reduced in the sham control group, but the effect was not sustained.

Surgery — Patients with intractable LARS despite all other treatments may require surgery. Surgical options include anal sphincter substitution and fecal diversion.

Anal sphincter substitution by electrostimulated graciloplasty or an artificial sphincter has been performed to treat intractable fecal incontinence, but not in LARS patients. The procedure is associated with a high complication rate and significant costs.

Fecal diversion by stoma is the option of last resort after all other treatment modalities have failed. It is only elected if the patient has low quality of life due to symptoms from major LARS after two years of conservative or minimally invasive (eg, SNS) treatment. (See "Overview of surgical ostomy for fecal diversion".)

PROGNOSIS — LARS can continue to affect patients long after the surgery has concluded. In a study of 242 patients who were followed for a median of 14.6 years after sphincter-sparing resection, major LARS was reported by 46 percent [3]. Active prevention, prompt diagnosis, and multimodal treatment of LARS will have a significant benefit to these patients' quality of life.

SUMMARY AND RECOMMENDATIONS

●Definition and epidemiology of low anterior resection syndrome – Low anterior resection syndrome (LARS) is a constellation of symptoms, such as fecal incontinence or urgency, frequent or fragmented bowel movements, emptying difficulties, and increased intestinal gas, that occur after a sphincter-sparing resection (ie, anterior resection) of the rectum. An estimated 25 to 80 percent of patients develop LARS following a sphincter-sparing rectal surgery, and symptoms persist beyond 10 years in 50 percent of patients. (See 'Definition' above and 'Epidemiology and risk factors' above.)

●Prevention of LARS – After a sphincter-sparing rectal resection, we suggest pelvic floor muscle training with home Kegel exercises for all patients (Grade 2C). Additionally, those who have a protective stoma that is not expected to close within one to two months should also receive daily or two- to three-times-per-week enemas or anterograde colonic irrigation via the stoma. (See 'Prevention' above.)

●Diagnosis of LARS – LARS should be suspected in patients who develop one or more bowel symptoms after undergoing a sphincter-sparing resection of the rectum. The diagnosis is confirmed after the symptom(s) persist for one month after surgery and an evaluation fails to elucidate an alternative etiology. (See 'Diagnosis and differential diagnosis' above and 'Diagnostic evaluation' above.)

●Diagnostic evaluation – At one month after the initial surgery or after the protective stoma is closed, patients who have persistent bowel symptoms should be formally evaluated with one of the patient questionnaires, such as the LARS score. Further treatment options are dependent upon the LARS score. Although anorectal/colonic manometry is not required to diagnose LARS, it can be helpful in monitoring patient response to treatment, especially for major LARS, when available (algorithm 1). (See 'Diagnostic evaluation' above.)

●Medical treatment of minor LARS – For patients with minor LARS (LARS score <30), we suggest medical treatment rather than more intensive or invasive modalities of therapy (Grade 2C). Medical treatments for minor LARS should be individualized for each patient based on symptoms:

•Diarrhea – Loperamide (first-line) or colesevelam (second-line) (see 'Diarrhea' above)

•Postprandial urgency or incontinence – One of the serotonin- (5-hydroxytryptamine)-3 receptor (5-HT₃) antagonists (eg, ramosetron) (see 'Postprandial urgency or incontinence' above)

•Gas and bloating – Antibiotics (eg, rifaximin or neomycin) (see 'Gas and bloating' above)

•Fecal soilage – Intra-anal injection of bulking agents (see 'Fecal soilage' above)

●Treatment of major LARS – For patients with major LARS (LARS score ≥30), we suggest intensive multimodal therapy including transanal irrigation and pelvic floor rehabilitation (Grade 2C). (See 'Colonic irrigation' above and 'Pelvic floor rehabilitation' above.)

•At one year, patients who continue to have major LARS should be offered a trial of sacral nerve stimulation (SNS) in addition to continued transanal irrigation and pelvic floor rehabilitation. (See 'Neurostimulation' above.)

•At two years, or one year after sacral nerve stimulation has been attempted, patients who continue to have major LARS associated with a low quality of life should be offered fecal diversion by stoma. (See 'Surgery' above.)