ABSTRACT
Low anterior resection syndrome (LARS) is a condition of anorectal dysfunction
that occurs frequently following anal sphincter-preserving surgery for rectal
cancer and can reduce the quality of life. In this review, we summarize the main
symptoms and pathophysiology of this syndrome and discuss the treatment
approaches. Early evaluation and initiation of appropriate treatment
postoperatively are crucial. The most frequently used tool to evaluate the
severity of LARS is the LARS score, and an anorectal manometer is used for
objective evaluation. LARS is believed to be caused by multiple factors, and
some of its causes include direct structural damage to the anal sphincter,
damage to the innervation, loss of rectoanal inhibitory reflex, and decreased
rectal volume and compliance. Diet modifications, medications, pelvic floor
muscle training and biofeedback are the primary treatments, and rectal
irrigation can be added as a secondary treatment. If LARS symptoms persist even
after 1 to 2 years and significantly reduce the quality of life, antegrade
irrigation, sacral nerve stimulation or definitive stoma may be considered.
High-quality evidence-based studies on LARS treatment are lacking, and
randomized controlled trials aimed at developing severity-based treatment
algorithms are needed.
The annual incidence of colorectal cancer (CRC) in Korea is 44.5 cases per 100,000
persons, which is one of the highest in the world [1]. According to a recent review article, the incidence of early onset
cancer per 100,000 people aged 20–49 years was 12.9, which was the highest of
42 countries that were investigated [2]. In
addition to stage 0-I CRC, locally advanced stage II-III CRC is also resected en
bloc together with surrounding organs or structures; therefore, surgical treatment
is the most important treatment for CRC [3].
Multidisciplinary approaches to the treatment of rectal cancer and improved surgical
techniques, including laparoscopic [4] and
robotic total mesorectal excision [5], have
improved the rate of local recurrence and postoperative complications [6] following rectal resection. Owing to the
development of surgical techniques and multimodal treatment in rectal cancer,
sphincter preservation surgery is preferred over abdominoperineal resection which
requires a permanent colostomy [7]. Up to 80%
of patients with rectal cancer have undergone sphincter preservation surgery [8] and up to 90% of them have impaired anorectal
function, which is called low anterior resection (LAR) syndrome (LARS) [9]. This review describes the definition,
epidemiology, risk factors, and evaluation tools of LARS and introduces treatments
with an emphasis on rehabilitation to improve LARS.
LARS is defined as “a combination of symptoms, such as increased frequency and
urgency of bowel movements, fecal incontinence, sense of incomplete emptying, and
fragmentation after rectal resection, which reduces the quality of life [10].” Patients with LARS can be divided
into two overlapping groups: those with urgency and fecal incontinence primarily,
and those with evacuatory dysfunction. Recently, an international consensus Delphi
process was conducted for patients who received LAR to refine the definition of
LARS. This study has defined eight symptoms and eight consequences considered the
highest priority in LARS, and are summarized in Table 1. To meet the definition of LARS, a patient receiving LAR should
experience at least one of these symptoms that result in at least one of these
consequence [11].
Since LARS is a syndrome that includes various symptoms, varying prevalence rates
have been reported depending on the evaluation tools used. Prevalence surveys using
the LARS questionnaire [12] have been
conducted in recent years. The reported prevalence of major LARS, the most severe
anorectal dysfunction, ranges from 17.8% to 56.0% [13–15]. According to the
most recent meta-analysis, the prevalence of major LARS was reported to be 44%
[15] and 41% [14], and the combined rate of minor and major LARS was reported
to be 65% [14].
Tools for evaluating LARS include the LARS score [12], Wexner score [16], Kirwan
classification [17], Fecal incontinence
severity index [18] and anal examination
scoring system (PASS) [19]. Of them, the LARS
score is a simple and valid scoring system, and it is a questionnaire that reflects
incontinence, frequent bowel movements, bowel emptying difficulties, and urges that
occur following LAR. It has been translated into Korean [20], validated, and used in several studies.
For objective evaluation, most studies have assessed the anorectal function using
manometry. The parameters assessed using anorectal manometry include resting
pressure, squeeze pressure, rectoanal inhibitory reflex (RAIR), rectal sensitivity
(first sensation volume, urge to defecate volume, and discomfort volume), and
compliance [21].
Although the exact pathophysiology of LARS is not fully understood, it is believed
that the symptoms result from multiple causes and mechanisms [10].
The internal anal sphincter (IAS) is an involuntary muscle that plays an
important role in maintaining resting continence. The internal sphincter is
contracted by the parasympathetic nerves of S2-4. The internal sphincter is
often resected during intersphincteric resection. It has been reported that
direct structural damage occurs during this procedure with a resultant lowering
of the resting pressure of the IAS. It is also known that the lower the
pressure, the more major LARS that occurs. Additionally, the direct damage
depends on the device used for anastomosis, such as a stapler, which results in
the lowering of the mean resting pressure of the IAS. Structural damage to the
IAS is evaluated using endosonography [22].
IAS function can also be impaired by damage to the autonomic nervous system. The
risk of damage to the sympathetic/parasympathetic nerves entering the rectal
wall is high during total mesorectal excision [23]. It is known that anal canal sensitivity is reduced secondary to
a loss of the sensory branch of the pudendal nerve, which is responsible for
sensations of the rectum, along with other nerves of the autonomic nervous
system, which result in significant effects on postoperative incontinence [24].
RAIR refers to temporary IAS relaxation due to rectal distention. This reflex
makes it possible to distinguish between liquids, solids, and gases. Although
the role of RAIR in incontinence is not well known, previous studies have
revealed many cases of RAIR loss following LAR [25]. Previous studies have demonstrated that the frequency of
soiling is higher in patients in whom RAIR does not recover and that RAIR loss
is a predictor of bowel dysfunction 1 year after LAR [26].
Rectal volume and compliance of the rectum serve as reservoirs for feces and
gases between evacuations. Surgical treatment reduces the maximal rectal volume
by removing varying lengths of the rectum [27], and radiotherapy reduces rectal compliance [28]. Reduced volume and compliance
correlate with urgency, frequency, and urge incontinence [29]. Additionally, the volume required to initiate the urge
to defecate is lowered in patients with LAR and further reduced in patients with
a short remnant rectum [30] and those who
undergone irradiation [28]. For this
reason, surgeons have developed techniques to increase the neorectal volume by
constructing a remnant rectum. Side-to-end anastomosis, colonic J-pouch, and
transverse coloplasty are known to significantly reduce bowel frequency for up
to 24 months postoperatively.
LAR involves ligation of the inferior mesenteric artery and sympathetic
denervation of the left colon. Studies conducted in rats to investigate the
changes in colonic motility following denervation confirmed that colonic
migrating contractions increased in the distal colon early after denervation,
which is the basis for multiple evacuations after LAR [31,32]. A previous
study evaluated the colonic motility following meals in patients with and
without an increase in stool frequency following LAR and in healthy controls
[33]. The results demonstrated that
colonic contractions proximal to the anastomosis site were increased in patients
who underwent LAR than those in healthy controls; additionally, colonic
contractions occurred earlier in patients with increased stool frequency who
underwent LAR than those in patients with normal stool frequency who underwent
LAR. In a study that evaluated the colonic transit time using single-photon
emission CT/CT scintigraphy, patients with major LARS had significantly faster
colonic transit time than those without LARS [34]. In cases of a longer denervated neorectum due to proximal
inferior mesenteric artery dissection, propagated contractions disappeared more
often and spastic minor contractions were higher in the neorectum [35], which correlated with the urgency of
defecation and multiple evacuations [36].
In recently published papers and systematic reviews, low tumor height and thus low
anastomotic height, and radiotherapy were the highest risk factors for LARS [14,15,37]. Furthermore, some studies
have identified anastomotic leak [38] and
diverting stoma as additional risk factors for LARS. The formation of a neorectal
pouch was more common with no functional advantage. Additionally, radiotherapy (OR,
2.89, 95% CI, 2.06–4.05), low tumor height (OR, 2.13, 95% CI,
1.49–3.04), anastomotic leak (OR, 1.98, 95% CI, 1.34–2.93), and
diverting stoma (OR, 1.89, 95% CI, 1.58–2.27) were associated with an
increased risk of major LARS [15].
A multimodal approach, rather than a single treatment, could represent the best
management option for patients with LARS. Diet modifications, medications, pelvic
floor muscle training (PFMT) and biofeedback are the primary treatments, and rectal
irrigation can be added as a secondary treatment. If LARS symptoms persist even
after 1 to 2 years and significantly reduce the quality of life, antegrade
irrigation, sacral nerve stimulation (SNS) or definitive stoma may be considered.
The treatment algorithm proposed by the author is shown in Fig. 1.
Self-care strategies and dietary modifications are the easiest and earliest
interventions for patients with LARS. Although the evidence is rare, these
strategies include the advantage of being simple and that they can be controlled
by the patient. It was reported that 96% of patients with rectal cancer who
underwent LAR changed their diet postoperatively [39]. It is important to avoid foods that stimulate the
bowels and loosen stools, such as alcohol, caffeine, and spicy foods. Although
studies on LARS are lacking, it is known that a high intake of soluble dietary
fibers (oats, peas, beans, apples, citrus fruits, carrots, barley, and psyllium)
in the general population is associated with a decreased riskof fecal
incontinence [40]; therefore, post-LAR,
patients are recommended to consume these foods.
Probiotics have also been evaluated based on the hypothesis that LARS is caused
by changes in the colonic mucosal physiology and the bacterial environment;
however, no significant difference was found in comparison with placebo.
Medications are the first-line treatment for LARS, which can be attempted when
symptoms cannot be controlled with self-care strategies, diet, or exercise.
Loperamide, a mu-opioid receptor agonist, is the most commonly prescribed drug
along with sitz baths or topical ointments and is the most effective therapy for
increased bowel frequency and incontinence [41]. Loperamide is believed to decrease colonic motility and
increase the tone of the IAS. Additionally, 5-HT3 antagonists (mosetron or
alosetron) are known to treat intestinal hypermobility. Recently, a randomized
controlled trial that included 100 patients with LARS who were treated with
ramosetron in Korea reported that it significantly reduced the proportion of
major LARS and improved the quality of life in comparison with the control group
[42].
Pelvic floor rehabilitation consists of PFMT, biofeedback, rectal balloon
retraining, and electrical stimulation aimed at improving pelvic floor muscle
strength and coordination and rectal sensations. PFMT includes external anal
sphincter strength training and isometric contraction exercises that strengthen
the pelvic floor muscles. It can be administered along with biofeedback or
electrical stimulation but can also be used as monotherapy. PFMT is thought to
improve LARS by enhancing structural support, timing, and strength of
autonomatic contractions [43]. The
important thing to note during exercise is not to hold breath, not to contract
the gluteal or abdominal muscles, and to have the same contraction and
relaxation time. The anorectal angle, the angle between the anal canal and the
rectum that is maintained by the puborectalis, is important for maintaining
continence. Repetitive voluntary contractions during PFMT and external anal
sphincter are believed to help improve incontinence by reducing the anorectal
angle during the resting state.
Biofeedback training is a therapy that uses electronic equipment to inform the
user of internal physiological events in the form of visual or auditory signals.
Biofeedback consists of rectal sensitivity, strength, and coordination training
[44]. Sensory training involves the
use of a rectal balloon that gradually inflates until the patient reports the
first sense of filling. Repeated re-inflation is performed to teach the patient
to feel inflation at progressively lower volumes. This allows the patient to
detect the need to pass stools at a lower threshold of filling. Strength
training is a process in which the patient contracts and relaxes the anal
sphincter to reach a target signal based on hearing or watching feedback. It is
also possible to receive feedback by attaching reference electrodes to the
abdominal or gluteal muscles such that no force is applied to the muscles other
than that from the pelvic floor muscles. Coordination training is a process in
which the patient contracts the abdominal muscles and relaxes the pelvic floor
muscles while evacuating the balloon from the rectum [45].
Transanal retrograde irrigation is a method of mechanical colon flushing using a
pump or an irrigation bag. A cone-shaped end attached to the distal tip is
inserted into the anal canal, and 500–1000 cc of water with a temperature
similar to the body temperature is injected. It is usually administered daily,
and the amount and frequency of water injected may vary between patients. The
patient is instructed to evacuate the rectum until urgency is felt. If it is
difficult to maintain a cone-shaped end, irrigation can be performed by
inserting a balloon catheter into the rectum. Rectal irrigation does not result
in true continence; rather, it produces pseudo-continence between washouts.
However, it is known to be safe and improve patients’ quality of life by
preventing nocturnal soiling, improving fecal incontinence, and regularizing of
defecation. Since patients irrigate large volumes by themselves, education
regarding the correct method is essential. The treatment algorithm used in one
study suggested that rectal irrigation could be performed 30 days after LAR
[46], but the algorithm in another
paper suggested that it should be performed after 6 months [37]. A recent study evaluated prophylactic
rectal irrigation early after stoma closure in high-risk patients with LARS and
reported that early rectal irrigation was safe and improved LARS [47].
Antegrade irrigation refers to daily irrigation using an external catheter after
performing percutaneous endoscopic colostomy (PEC). The largest case series
report of antegrade irrigation in rectal cancer was a study involving 25
patients, of which 4 (16%) had catheters removed, meaning that the procedure was
ineffect in 16%. LARS score significantly decreased from 33 to 4 after PEC
procedure and antegrade irrigation, and rate of major LARS decreased
significantly from 73% to 9%. However, PEC shoulder be chosen carefully as there
are some complications such as local pain, sweating, granulation at the PEC
entry, leakage, and wound infection [48].
Given the evidence that SNS affects not only the anus and rectum but also the
upper gastrointestinal tract and colon, the effects of SNS on anorectal function
appear to originate at the pelvic afferent or central level. Recently, a
systematic review article on studies that used SNS to improve LARS was published
[49]. Before permanent SNS
implantation, a temporary electrode was inserted through the S3 foramen to
confirm the effectiveness of SNS, and percutaneous nerve evaluation (PNE) was
performed. Permanent SNS was implanted when PNE confirmed improvement in fecal
incontinence. A total of 94 patients underwent PNE and 79.8% of them underwent
permanent SNS implantation. Although each study was different, stimulation was
used with a pulse width of 210 µs and a frequency of 14 pulses/s; the
amplitude was controlled by determining the degree to which the patient felt
perineal and anal sphincter contractions. Although the studies included in the
systematic review were not randomized controlled trials and the sample size was
small, it is a meaningful result that the degree of fecal incontinence and LARS
score improved significantly with implantation, especially because the patients
who received SNS had chronic LARS. The use of SNS can be a treatment option in
patients with refractory LARS.
Tibial nerve stimulation (TNS) is a novel, cost-effective and less invasive form
of indirect neuromodulation of sacral nerve function. The tibial nerve is a
mixture of sensory and motor nerves originating from the L4 to S3 spinal nerve
roots, overlapping with the from S2 to S4 spinal nerve roots, from which nerves
to the pelvic floor muscle and sphincter originate. TNS is thought to improve
the resing and stress pressure of the sphincter and enhance rectal sensitivity
by triggering multiple nerve pathways at the medulla and brain levels. TNS can
modulate higher perception of afferent information and is thought to modulate
colonic motility by triggering local somato-visceral reflexes [50]. A small electrode is inserted close to
the posterior tibial nerve at ankle level and stimulated for 30 minutes, once a
week, for a total of 16 to 20 times. Stimulation was used with a pulse width of
200 µs and a frequency of 20 pulses/s; the amplitude was ranged from 0.5
to 9.0 mA. Two of the three randomized controlled trials had no significant
effect, and in one study, only the TNS group had a positive result that
improvement of LARS and fecal incontinence scores were maintained up to 12
months [50].
With an increasing number of patients receiving neoadjuvant concurrent
chemoradiotherapy and sphincter-preserving surgery for rectal cancer, the number of
patients with a reduced quality of life due to LARS is increasing. After appropriate
evaluations, it is important to provide treatment according to the postoperative
duration and severity of LARS. Further studies are required to improve the level of
evidence.
References
1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence
and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018; 68(6):394–424. DOI: 10.3322/caac.21492. PMID: 30207593.
2. Patel SG, Karlitz JJ, Yen T, Lieu CH, Richard Boland C. The rising tide of early-onset colorectal cancer: a comprehensive
review of epidemiology, clinical features, biology, risk factors,
prevention, and early detection. Lancet Gastroenterol Hepatol. 2022; 7(3):262–274. DOI: 10.1016/S2468-1253(21)00426-X.
3. Purkayastha J, Singh PR, Talukdar A, Das G, Yadav J, Bannoth S. Feasibility and outcomes of multivisceral resection in locally
advanced colorectal cancer: experience of a tertiary cancer center in
North-East India. Ann Coloproctol. 2020; 37(3):174–178. DOI: 10.3393/ac.2020.06.03. PMID: 34111348. PMCID: PMC8273713.
4. Tan HCL, Tan JH, Nur Dzainuddin NA, Chan KK. First feasibility study and short-term outcomes of
laparoscopic-assisted anterior resection in colorectal cancer in
Malaysia. Ann Coloproctol. 2020; 36(2):94–101. DOI: 10.3393/ac.2019.05.10. PMID: 32178501. PMCID: PMC7299566.
5. Jang JH, Kim CN. Robotic total mesorectal excision for rectal cancer: current
evidences and future perspectives. Ann Coloproctol. 2020; 36(5):293–303. DOI: 10.3393/ac.2020.06.16. PMID: 33207112. PMCID: PMC7714377.
6. Oh CK, Huh JW, Lee YJ, Choi MS, Pyo DH, Lee SC, et al. Long-term oncologic outcome of postoperative complications after
colorectal cancer surgery. Ann Coloproctol. 2020; 36(4):273–280. DOI: 10.3393/ac.2019.10.15. PMID: 32054256. PMCID: PMC7508476.
7. Piozzi GN, Kim SH. Robotic intersphincteric resection for low rectal cancer:
technical controversies and a systematic review on the perioperative,
oncological, and functional outcomes. Ann Coloproctol. 2021; 37(6):351–367. DOI: 10.3393/ac.2021.00836.0119. PMID: 34784706. PMCID: PMC8717069.
8. Varela C, Kim NK. Surgical treatment of low-lying rectal cancer:
updates. Ann Coloproctol. 2021; 37(6):395–424. DOI: 10.3393/ac.2021.00927.0132. PMID: 34961303. PMCID: PMC8717072.
9. Bregendahl S, Emmertsen KJ, Lous J, Laurberg S. Bowel dysfunction after low anterior resection with and without
neoadjuvant therapy for rectal cancer: a population-based cross-sectional
study. Colorectal Dis. 2013; 15(9):1130–1139. DOI: 10.1111/codi.12244. PMID: 23581977.
10. Bryant CLC, Lunniss PJ, Knowles CH, Thaha MA, Chan CLH. Anterior resection syndrome. Lancet Oncol. 2012; 13(9):E403–E408. DOI: 10.1016/S1470-2045(12)70236-X.
11. Keane C, Fearnhead NS, Bordeianou L, Christensen P, Espin Basany E, Laurberg S, et al. International consensus definition of low anterior resection
syndrome. Colorectal Dis. 2020; 22(3):331–341. DOI: 10.1111/codi.14957. PMID: 32037685.
12. Emmertsen KJ, Laurberg S. Low anterior resection syndrome score: development and validation
of a symptom-based scoring system for bowel dysfunction after low anterior
resection for rectal cancer. Ann Surg. 2012; 255(5):922–928. DOI: 10.1097/SLA.0b013e31824f1c21. PMID: 22504191.
13. Chen TYT, Wiltink LM, Nout RA, Kranenbarg EMK, Laurberg S, Marijnen CAM, et al. Bowel function 14 years after preoperative short-course
radiotherapy and total mesorectal excision for rectal cancer: report of a
multicenter randomized trial. Clin Colorectal Cancer. 2015; 14(2):106–114. DOI: 10.1016/j.clcc.2014.12.007. PMID: 25677122.
14. Croese AD, Lonie JM, Trollope AF, Vangaveti VN, Ho YH. A meta-analysis of the prevalence of low anterior resection
syndrome and systematic review of risk factors. Int J Surg. 2018; 56:234–241. DOI: 10.1016/j.ijsu.2018.06.031. PMID: 29936195.
15. Sun R, Dai Z, Zhang Y, Lu J, Zhang Y, Xiao Y. The incidence and risk factors of low anterior resection syndrome
(LARS) after sphincter-preserving surgery of rectal cancer: a systematic
review and meta-analysis. Support Care Cancer. 2021; 29(12):7249–7258. DOI: 10.1007/s00520-021-06326-2. PMID: 34296335.
16. Jorge MJN, Wexner SD. Etiology and management of fecal incontinence. Dis Colon Rectum. 1993; 36(1):77–97. DOI: 10.1007/BF02050307. PMID: 8416784.
17. Kirwan WO, Turnbull RB Jr, Fazio VW, Weakley FL. Pullthrough operation with delayed anastomosis for rectal
cancer. Br J Surg. 1978; 65(10):695–698. DOI: 10.1002/bjs.1800651008. PMID: 709078.
18. Rockwood TH, Church JM, Fleshman JW, Kane RL, Mavrantonis C, Thorson AG, et al. Patient and surgeon ranking of the severity of symptoms
associated with fecal incontinence: the fecal incontinence severity
index. Dis Colon Rectum. 1999; 42(12):1525–1531. DOI: 10.1007/BF02236199. PMID: 10613469.
19. Eldamshety O, Kotb S, Khater A, Elnahas W, Roshdy S, Zahi MS, et al. Early and late functional outcomes of anal sphincter-sparing
procedures with total mesorectal excision for anorectal
adenocarcinoma. Ann Coloproctol. 2020; 36(3):148–154. DOI: 10.3393/ac.2018.07.19. PMID: 32311866. PMCID: PMC7392569.
20. Kim CW, Jeong WK, Son GM, Kim IY, Park JW, Jeong SY, et al. Validation of Korean version of low anterior resection syndrome
score questionnaire. Ann Coloproctol. 2020; 36(2):83–87. DOI: 10.3393/ac.2019.08.01. PMID: 32054239. PMCID: PMC7299562.
21. Ihnát P, Vávra P, Prokop J, Pelikán A, Ihnát Rudinská L, Penka I. Functional outcome of low rectal resection evaluated by anorectal
manometry. ANZ J Surg. 2017; 88(6):E512–E516. DOI: 10.1111/ans.14207. PMID: 28922706.
22. Farouk R, Duthie GS, Lee PW, Monson JR. Endosonographic evidence of injury to the internal anal sphincter
after low anterior resection: long-term follow-up. Dis Colon Rectum. 1998; 41(7):888–891. DOI: 10.1007/BF02235373. PMID: 9678375.
23. Bharucha AE, Blandon RE, Lunniss PJ, Mark Scott S. Anatomy and physiology of continence. In. In : Ratto C, Doglietto GB, Lowry AC, Påhlman L, Romano G, editors. editors. Fecal incontinence. Milano: Springer;2007. p. p. 3–16. DOI: 10.1007/978-88-470-0638-6_1.
24. Tomita R, Igarashi S, Fujisaki S. Studies on anal canal sensitivity in patients with or without
soiling after low anterior resection for lower rectal cancer. Hepato-Gastroenterology. 2008; 55(85):1311–1314.
25. Otto IC, Ito K, Ye C, Hibi K, Kasai Y, Akiyama S, et al. Causes of rectal incontinence after sphincter-preserving
operations for rectal cancer. Dis Colon Rectum. 1996; 39(12):1423–1427. DOI: 10.1007/BF02054533. PMID: 8969670.
26. Kakodkar R, Gupta S, Nundy S. Low anterior resection with total mesorectal excision for rectal
cancer: functional assessment and factors affecting outcome. Colorectal Dis. 2006; 8(8):650–656. DOI: 10.1111/j.1463-1318.2006.00992.x. PMID: 16970574.
27. Lee SJ, Park YS. Serial evaluation of anorectal function following low anterior
resection of the rectum. Int J Colorectal Dis. 1998; 13(5-6):241–246. DOI: 10.1007/s003840050169. PMID: 9870169.
28. Ihnát P, Slívová I, Tulinsky L, Ihnát Rudinská L, Máca J, Penka I. Anorectal dysfunction after laparoscopic low anterior rectal
resection for rectal cancer with and without radiotherapy (manometry
study). J Surg Oncol. 2017; 117(4):710–716. DOI: 10.1002/jso.24885. PMID: 29094352.
29. Chan CLH, Lunniss PJ, Wang D, Williams NS, Scott SM. Rectal sensorimotor dysfunction in patients with urge faecal
incontinence: evidence from prolonged manometric studies. Gut. 2005; 54(9):1263–1272. DOI: 10.1136/gut.2005.071613. PMID: 15914573. PMCID: PMC1774666.
30. Nesbakken A, Nygaard K, Lunde OC. Mesorectal excision for rectal cancer: functional outcome after
low anterior resection and colorectal anastomosis without a
reservoir. Colorectal Dis. 2002; 4(3):172–176. DOI: 10.1046/j.1463-1318.2002.00305.x. PMID: 12780611.
31. Lee WY, Takahashi T, Pappas T, Mantyh CR, Ludwig KA. Surgical autonomic denervation results in altered colonic
motility: an explanation for low anterior resection
syndrome? Surgery. 2008; 143(6):778–783. DOI: 10.1016/j.surg.2008.03.014. PMID: 18549894.
32. Shimizu K, Koda K, Kase Y, Satoh K, Seike K, Nishimura M, et al. Induction and recovery of colonic motility/defecatory disorders
after extrinsic denervation of the colon and rectum in rats. Surgery. 2006; 139(3):395–406. DOI: 10.1016/j.surg.2005.08.018. PMID: 16546505.
33. Mochiki E, Nakabayashi T, Suzuki H, Haga N, Fujita K, Asao T, et al. Barostat examination of proximal site of the anastomosis in
patients with rectal cancer after low anterior resection. World J Surg. 2001; 25(11):1377–1382. DOI: 10.1007/s00268-001-0144-y. PMID: 11760737.
34. Ng KS, Russo R, Gladman MA. Colonic transit in patients after anterior resection:
prospective, comparative study using single-photon emission CT/CT
scintigraphy. Br J Surg. 2020; 107(5):567–579. DOI: 10.1002/bjs.11471. PMID: 32154585.
35. Koda K, Saito N, Seike K, Shimizu K, Kosugi C, Miyazaki M. Denervation of the neorectum as a potential cause of defecatory
disorder following low anterior resection for rectal cancer. Dis Colon Rectum. 2005; 48(2):210–217. DOI: 10.1007/s10350-004-0814-6. PMID: 15711859.
36. Iizuka I, Koda K, Seike K, Shimizu K, Takami Y, Fukuda H, et al. Defecatory malfunction caused by motility disorder of the
neorectum after anterior resection for rectal cancer. Am J Surg. 2004; 188(2):176–180. DOI: 10.1016/j.amjsurg.2003.12.064. PMID: 15249246.
37. Nguyen TH, Chokshi RV. Low anterior resection syndrome. Curr Gastroenterol Rep. 2020; 22(10):48. DOI: 10.1007/s11894-020-00785-z. PMID: 32749603. PMCID: PMC8370104.
38. Kim S, Kang SI, Kim SH, Kim JH. The effect of anastomotic leakage on the incidence and severity
of low anterior resection syndrome in patients undergoing proctectomy: a
propensity score matching analysis. Ann Coloproctol. 2021; 37(5):281–290. DOI: 10.3393/ac.2021.03.15. PMID: 34098631. PMCID: PMC8566143.
39. Yin L, Fan L, Tan R, Yang G, Jiang F, Zhang C, et al. Bowel symptoms and self-care strategies of survivors in the
process of restoration after low anterior resection of rectal
cancer. BMC Surg. 2018; 18(1):35. DOI: 10.1186/s12893-018-0368-5. PMID: 29866087. PMCID: PMC5987619.
40. Staller K, Song M, Grodstein F, Whitehead WE, Matthews CA, Kuo B, et al. Increased long-term dietary fiber intake is associated with a
decreased risk of fecal incontinence in older women. Gastroenterology. 2018; 155(3):661–667. DOI: 10.1053/j.gastro.2018.05.021. PMID: 29758215.
41. Garfinkle R, Dell’Aniello S, Bhatnagar S, Morin N, Ghitulescu G, Faria J, et al. Assessment of long-term bowel dysfunction after restorative
proctectomy for neoplastic disease: a population-based cohort
study. Surgery. 2022; 172(3):782–788. DOI: 10.1016/j.surg.2021.10.068. PMID: 34848073.
42. Ryoo SB, Park JW, Lee DW, Lee MA, Kwon YH, Kim MJ, et al. Anterior resection syndrome: a randomized clinical trial of a
5-HT3 receptor antagonist (ramosetron) in male patients with rectal
cancer. Br J Surg. 2021; 108(6):644–651. DOI: 10.1093/bjs/znab071. PMID: 33982068.
43. Dulskas A, Smolskas E, Kildusiene I, Samalavicius NE. Treatment possibilities for low anterior resection syndrome: a
review of the literature. Int J Colorectal Dis. 2018; 33(3):251–260. DOI: 10.1007/s00384-017-2954-x. PMID: 29313107.
44. Hite M, Curran T. Biofeedback for pelvic floor disorders. Clin Colon Rectal Surg. 2021; 34(1):56–61. DOI: 10.1055/s-0040-1714287. PMID: 33536850. PMCID: PMC7843943.
45. Nishigori H, Ishii M, Kokado Y, Fujimoto K, Higashiyama H. Effectiveness of pelvic floor rehabilitation for bowel
dysfunction after intersphincteric resection for lower rectal
cancer. World J Surg. 2018; 42(10):3415–3421. DOI: 10.1007/s00268-018-4596-8. PMID: 29556878.
46. Martellucci J. Low anterior resection syndrome: a treatment
algorithm. Dis Colon Rectum. 2016; 59(1):79–82. DOI: 10.1097/DCR.0000000000000495. PMID: 26651116.
47. Rosen HR, Kneist W, Fürst A, Krämer G, Hebenstreit J, Schiemer JF. Randomized clinical trial of prophylactic transanal irrigation
versus supportive therapy to prevent symptoms of low anterior resection
syndrome after rectal resection. BJS Open. 2019; 3(4):461–465. DOI: 10.1002/bjs5.50160. PMID: 31388638. PMCID: PMC6677104.
48. Didailler R, Denost Q, Loughlin P, Chabrun E, Ricard J, Picard F, et al. Antegrade enema after total mesorectal excision for rectal
cancer: the last chance to avoid definitive colostomy for refractory low
anterior resection syndrome and fecal incontinence. Dis Colon Rectum. 2018; 61(6):667–672. DOI: 10.1097/DCR.0000000000001089. PMID: 29722725.
49. Huang Y, Koh CE. Sacral nerve stimulation for bowel dysfunction following low
anterior resection: a systematic review and meta-analysis. Colorectal Dis. 2019; 21(11):1240–1248. DOI: 10.1111/codi.14690. PMID: 31081580.
50. Tazhikova A, Makishev A, Bekisheva A, Dmitriyeva M, Toleubayev M, Sabitova A. Efficacy of tibial nerve stimulation on fecal incontinence in
patients with low anterior resection syndrome following surgery for
colorectal cancer. Ann Rehabil Med. 2022; 46(3):142–153. DOI: 10.5535/arm.22025. PMID: 35793903. PMCID: PMC9263329.