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Background:
Systematic Review

Transanal Irrigation in Patients with Low Anterior Resection Syndrome After Rectal-Sphincter-Preserving Surgery for Oncological and Non-Oncological Disease: A Systematic Review

by
Andrea Morini
1,*,
Massimiliano Fabozzi
1,
Magda Zanelli
2,
Francesca Sanguedolce
3,
Andrea Palicelli
2,
Alfredo Annicchiarico
4,5,
Candida Bonelli
6 and
Maurizio Zizzo
1
1
Surgical Oncology Unit, Reggio Emilia Local Agency—IRCCS Advanced Technologies and Care Models in Oncology, 42123 Reggio Emilia, Italy
2
Pathology Unit, Reggio Emilia Local Agency—IRCCS Advanced Technologies and Care Models in Oncology, 42123 Reggio Emilia, Italy
3
Pathology Unit, Policlinico Riuniti, University of Foggia, 71122 Foggia, Italy
4
Department of Medicine and Surgery, University of Parma, 43125 Parma, Italy
5
Department of General Surgery, Vaio Hospital, Fidenza, 43125 Parma, Italy
6
Oncology Department, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy
*
Author to whom correspondence should be addressed.
Surg. Tech. Dev. 2024, 13(4), 409-425; https://doi.org/10.3390/std13040033
Submission received: 30 September 2024 / Revised: 28 November 2024 / Accepted: 18 December 2024 / Published: 22 December 2024
Browse Figure
Versions Notes

Abstract

:
Background/Objectives: Transanal irrigation (TAI) has been recognized as a safe and effective treatment for neurological bowel dysfunction, chronic constipation or fecal incontinence and has also been proposed for patients with low anterior resection syndrome (LARS). The aim of the present systematic review was to evaluate the feasibility and effectiveness of TAI in patients with significant LARS symptoms. Methods: We performed a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and guidelines in addition to the Cochrane Handbook for Systematic Reviews of Interventions. The protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42023436839). The risk of bias was assessed using a modified version of the Downs and Black checklist. The main outcome was improvement in low anterior resection syndrome after TAI assessed by change in LARS score. Results: After an initial screening of 3703 studies, 9 were included and underwent qualitative synthesis (among them, 3 were randomized clinical trials). All studies recorded an improvement in LARS score following TAI procedure and almost all studies showed an improvement in other bowel function outcomes (Memorial Sloan Kettering Cancer Center Bowel Function Instrument (MSKCC BFI, ), Cleveland Clinic Incontinence Score (CCIS), visual analog scale (VAS), Cleveland Clinic Florida Fecal Incontinence Score (CCFFIS), fecal incontinence score (FI score), Obstructed Defecation Syndrome (ODS) score) and quality of life (QoL) scores. The discontinuation rate ranged from 0% to 41%. The rate of adverse events was high (from 0 to 93%); moreover, no uniformity was found in the various protocols used among the different studies. Conclusions: The results of this review show that TAI is effective in the treatment of LARS, improving the LARS score, the other bowel function outcomes and the QoL scores. The absence of a treatment protocol validated by the scientific community is reflected in the high disparity in terms of adverse events and discontinuation of therapy, in addition to representing an intrinsic limitation to the study itself.

1. Introduction

Colorectal cancer ranks third among most common cancer types and approximately 30% of patients develop cancer in the rectum [1]. Modern rectal surgery was studied by Heald [2,3] in 1982, and the treatment of rectal cancer has been improved since then by multimodal approaches, including neoadjuvant chemoradiotherapy followed by total mesorectal excision (TME) [4,5]. Progress in healthcare led to a decreased rate of locoregional recurrences and better oncological prognoses [6], in addition to an increased rate of rectal-sphincter-preserving surgery (RSPS), thus ruling out definitive colostomies [7,8,9].
Benefits of RSPS are counterbalanced by post-operative impaired intestinal function, which negatively impacts quality of life (QoL) [10]. Symptoms are different and include fecal incontinence, fecal urgency, constipation, frequent bowel movements, clustering of stool and others [11]. The scientific literature defines such a spectrum of symptoms as Low Anterior Resection Syndrome (LARS), which is defined as a disorder of bowel function following rectal resection resulting in a lowering of QoL [12]. LARS records high rates (60–90%), and it can last for many years and can lead to permanent stoma in 5% of cases [13,14,15,16].
In 2020, a large international trilingual Delphi consensus process defined LARS as a unisymptomatic or polisymptomatic syndrome with one or more consequences following anterior resection [17]. Nevertheless, LARS identification both before and after Keane et al.’s definition required the LARS scoring system (a patient-reported bowel-related impairment) [18]. It consisted of five plain multiple-choice questions, whose validation was written in more than 35 languages, while 0–42 point scoring aimed at identifying three categories: “no LARS” (0–20), “minor LARS” (21–29) and “major LARS” (30–42) [18].
Although it is frequently used, the LARS scoring system has drawbacks, as it is ineffective in evaluating sexual and urinary dysfunction, which often co-exist in patients undergoing anterior rectal resection [19]. Furthermore, the LARS scoring system has not shown any consistent relationships between increasing LARS categories and worse QoL [20] so far.
At present, LARS treatment represents a challenge, while available multimodal approaches are as follows: diet, laxatives, constipation agents, medication (such as 5-HT3 antagonists or bile-acid sequestrants), pelvic floor rehabilitation, transanal irrigation (TAI), sacral nerve stimulation (SNS), percutaneous tibial nerve stimulation (PTNS) or stoma [21].
TAI promotes fecal evacuation by introducing water into the colon and rectum through an anus-inserted catheter [22]. It has already been suggested as treatment for neurological bowel dysfunction (NBD), both the congenital condition (spina bifida, multiple sclerosis, Parkinson’s disease) and the acquired one (spinal cord injury) or in the treatment of functional disorders, such as chronic constipation (CC) or fecal incontinence (FI) following gynecological or urological surgery, prolapse disease or idiopathic forms [23,24]. Being a therapeutic method for adult patients affected by NBD, FI or CC, TAI turns out as effective if compared to standard conservative treatments [25,26]. Based on the good outcomes in patients, TAI has also been used for patients suffering from LARS [27].
To date, only a few publications in the literature have assessed the safety and efficacy of TAI in patients with LARS following RSPS. There is currently no standardized TAI treatment protocol for patients with LARS. Furthermore, there is no standardized approach for follow-up timelines, leading to variability in the reported outcomes.
Our systematic review aimed for TAI feasibility and effectiveness in adult LARS patients with a history of RSPS.

2. Materials and Methods

Our systematic review had the following aims: systematically analyze available evidence and provide an overall assessment of TAI effectiveness in adult LARS patients with a history of RSPS and make a comparison (in case of comparative studies) with conservative management, standard of care (SoC) or other active approaches.
Our systematic review was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement [28] and guidelines in addition to the Cochrane Handbook for Systematic Reviews of Interventions [29]. The protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42023436839).
As our systematic review was based on previously published studies without any addition to the original patient population data, approval by an ethics committee and informed consent were not required.

2.1. Search Strategy

In October 2023, MEDLINE (via PubMed), EMBASE and Web of Science (Science and Social Science Citation Index) were systematically searched for any relevant human clinical study aimed at evaluating TAI effectiveness and/or comparing TAI and SC/other active treatments in patients with LARS following RSPS.
A reference list of relevant studies was manually searched and the Pubmed “related articles” function was used. In addition, the reference lists from the selected articles were also scrutinized. The research strategy envisaged an “all fields” search, including medical subject headings (MeSHs) and keywords, using terms such as “low anterior resection syndrome”, OR “LARS” OR “faecal incontinence” AND “transanal irrigation”. No restriction was placed on publication status or language. Full-text articles in languages other than English and with title/abstract indicating fulfillment of eligibility criteria were electronically translated.

2.2. Inclusion Criteria

According to the PICOS framework, the clinical factors were:
  • (P) Population: patients with LARS, after RSPS;
  • (I) Intervention: TAI as LARS treatment;
  • (C) Comparison: conservative management (standard of care) or placebo or any other active treatments for LARS;
  • (O) Outcomes, as reported in included studies: LARS improvement, assessed by change in LARS score;
  • (S) Studies: comparative and non-comparative population studies (case series, case-control studies, cohort studies, controlled clinical trials and randomized clinical trials).
We ruled out abstracts, posters, letters to the editor, study protocols, non-human studies, editorials, case reports, previously published systematic reviews and/or meta-analyses, studies that included other types of bowel dysfunction or neurogenic conditions and studies that did not include the LARS score as a LARS measure. In the case patients pooled in the TAI group were treated by other methods, studies were ruled out, although previously published systematic reviews or meta-analyses were taken into account in order to identify comparative studies left out through our systematic search.

2.3. Endopoints

The primary endpoint was TAI effect size on LARS score. The secondary endpoints included TAI effect size on bowel function scores and quality of life (QoL) scores

2.4. Data Extraction

All stages of study identification, selection, quality assessment, and data extraction were carried out by two independent reviewers (AM and AA). Inconsistencies were overcome through discussion between the two reviewers until consensus was reached. A double-blinded method was followed to increase data accuracy, which led to high and satisfactory inter-observer agreement (Kappa = 0.92).
The identified studies were then selected based on title, abstract, and full-text review in the Rayyan web app for systematic reviews (https://www.rayyan.ai/, accessed on 10 October 2023) [30], which was also used for manual removal of duplicate publications and article screening.
In case two or more studies overlap in patient cohorts with no difference in study period, the most recent report was included in the pooled analysis. Secondary analyses from ruled out studies were also included whenever they focused on outcomes other than those analyzed in the primary study.
Demographic and baseline characteristics included the following predefined data:
(1)
Study identifier (first author, nationality, year of publication, study type, study period, inclusion criteria, exclusion criteria, intervention, comparator, analyzed outcomes, follow-up times);
(2)
Baseline demographics characteristics of enrolled patients (population size, sex, age)
(3)
Outcome measures and baseline LARS data: baseline fecal incontinence score (FI score), Obstructive Defecation Syndrome (ODS) score, and quality of life (QoL) data; type of treatment of LARS (other than TAI); change in LARS scores after treatment; change in fecal incontinence score (FI score), Obstructive Defecation Syndrome (ODS) score and quality of life (QoL) after treatment; and follow-up duration in months
A third independent reviewer (MZ) eventually reviewed all collected results.
Inconsistencies were resolved through discussion between the two reviewers until consensus was reached.

2.5. Quality Assessment

The risk of bias was assessed using a modified version of the Downs and Black checklist [31] developed to evaluate the risk of bias for non-randomized and randomized control trials. The checklist is comprised of 27 questions designed to evaluate reporting and selection bias, along with the external and internal validity of an article. A higher score on the Downs and Black checklist is associated with higher quality evidence. In the present version, item 27 addressing statistical power was modified: one point was awarded if a power calculation was conducted and zero if it was not. The assessment was independently performed by two reviewers (AM and MZ). Disagreements were solved by consensus discussion between the two authors or by a third party (MF).

3. Results

3.1. Search Results

According to the final literature search, carried out in October 2023, we recorded 3703 possibly interesting studies (PubMed/MEDLINE: 341 records; Web of Science: 3182 records; Embase: 180 records) (Figure 1) [28]. Out of these, 244 were ruled out as duplicate publications. Furthermore, 3432 turned out to be irrelevant for title and abstract, while 27 full texts were considered eligible. As 18 studies did not comply with inclusion criteria, just 9 underwent qualitative synthesis [32,33,34,35,36,37,38,39,40]. No additional records were found through other sources (reference lists).

3.2. Quality of Studies

The modified version of the Downs and Black checklist obtained scores ranging from 14 to 26. Specifically, one of the studies was deemed of poor quality (≤14 points) [36], three were of fair quality (15–19) points [33,35,38], four were good quality studies (20–25 points) [32,34,37,39] and one was of excellent quality [40] (see Supplementary Materials, Table S1).

3.3. Study and Population Characteristics

Table 1 and Table 2 show the nine included studies and their features. Two studies were retrospective in nature [35,36] and four were prospective [32,33,37,38], while three studies were RCTs [34,39,40]. Four studies were multicentric in nature [34,38,39,40] and four were comparative [33,34,39,40]. Seven studies stemmed from Europe, one from the UK and one from Brazil, covering almost 30 years of observation (2003–2023). The first publication dated back to 2018, while the last one dated to 2023. Inclusion criteria, demographics population characteristics, neoadjuvant chemo-radiotherapy and follow-up times are also reported in Table 1. Among the four comparative studies, three compared with SoC [33,39,40] and one with PTNS [34].

3.4. Outcomes

General features and outcomes of studies (sample size, type of irrigation system, procedure of transanal irrigation, LARS score, bowel and QoL scores, discontinuation and adverse events) under analysis are shown in Table 3. The pooled population included 261 patients. As inclusion criteria, all studies recorded LARS score before TAI and following it, while all studies recorded an improvement following the TAI procedure (Table 3).
Concerning bowel function score/questionnaires, one study used St. Marks score [32], two studies used the Cleveland Clinic Florida Fecal Incontinence Score (CCFFIS) [35,39], one study employed an FI score (Vaizey) and ODS score (Altomare) [33] and one study used the Memorial Sloan Kettering Cancer Center Bowel Function Instrument (MSKCC BFI) [31]. Concerning studies that reported bowel function score questionnaires, outcomes are recorded in Table 3.
Outcome analysis between pre-treatment and post-treatment LARS score among comparative studies is shown in Table 4.
Meurette et al. reported a statistically significant improvement at 3-month follow-up in LARS score among patients undergoing TAI (from a mean LARS score of 37.4 (35.5, 39.2) to 21.3 (14.7, 27.8) (95% CI)) compared to those undergoing SoC TAI (from a mean LARS score of 39.2 (37.5, 40.9) to 32.2 (27.3, 37.1) (95% CI) (p = 0.008) [39]) (Table 3). Pieniowski et al. recorded an improved LARS score, both at 6 and 12 months. At a 6-month follow-up, the difference in mean LARS score (95% CI) recorded −11.3 (−17.1 to −5.6), and at a 12-month follow-up, the difference in mean LARS score (95% CI) was −9.5 (−15.2 to −3.7) in a comparison between patients undergoing TAI and those undergoing SoC [40] (Table 4). At 6-month follow-up, McCutchan et al. recorded an improved LARS score among patients undergoing TAI that ranged from 35.93 (21–42) to 17.73 (0–41) when compared to patients undergoing SoC, whose rate decreased from 34.17 (32–37) to 32.35 (26–37) [33] (Table 4). Enriquez-Navascues et al., who compared TAI with PTNS at 6-month follow-up, reported a statistically significant improved LARS score among TAI patients (p = 0.021) and also among PTNS patients (p = 0.045), although the TAI group witnessed a higher number of patients with reduced major LARS to minor or no LARS (8 vs. 3) [34] (Table 4).

3.5. Features of TAI Method

Out of the nine studies included in our systematic review, eight indicated the type of tool used for TAI [32,33,34,36,37,38,39,40]. With the exception of Rodrigues et al. [37], who took into account an ostomy irrigation system, all other authors used the Peristeen© irrigation systems (Coloplast) [32,33,34,36,38,39,40] (Table 3). A description of the TAI procedure was reported by five studies [32,34,36,37,38,39,40] (Table 3). The discontinuation rate (from 0% to 41%) was reported by all the studies [32,33,34,35,36,37,38,39,40], while five studies recorded the rate of adverse events (ranging from 0 to 93%) [33,34,36,39,40] (Table 3).

4. Discussion

Regulation of anal continence is a complex physiological process involving multiple factors. [41]. Alteration of functional homeostasis created after RSPS therefore has a multifactorial etiology [41]. Following RSPS with TME, rectum reservoir function is lost, which determines less storage, disturbed evacuation and impaired rectal compliance [41]. Scientific studies tried to adopt reconstruction techniques with a reservoir, without obtaining long-term benefits, but only advantages in immediate post-operative period and no confirmation with randomized data were observed [42,43]. The “rectosigmoid brake”, a functional sphincter situated at the sigmoid-rectus passage, is also missing. Its absence leads to a decrease in cyclic motor patterns (CMPs), which are crucial for supporting the continence function [44,45]. Additionally, the denervation of the parasympathetic and sympathetic autonomic nervous systems can result in hyperactivity and adverse effects on intestinal function [45,46]. Factors that are not related to surgery, such as radiotherapy or presence of a protective stoma, may influence the regulation of anal continence. Due to induced fibrosis, radiotherapy seems to cause related neuropathies and variations in colon wall and mesentery [41,45,47,48]. Presence of protective ileostomy and time between its preparation and its closure can create dysbiosis and consequent mucosa atrophy [49,50]. Considering the multifactorial etiogenesis of LARS, the suggested approach is based on a step-by-step escalation of treatments. Both the Christensen guidelines (MANUEL guidelines) [41] and the Hariji therapeutic program (Boreal program) [51] suggest that specific dietary intake (high-fiber, low-fat food and abstaining from wine, cold beverages and spicy or stimulating food), specific medications (laxatives or constipating agents, 5-HT3 antagonists or probiotics) may be considered the first therapeutic measures [41,51]. Despite this, the previously mentioned approaches appear to be inadequate in improving patients’ symptoms and QoL [52]. Pelvic floor rehabilitation through pelvic floor muscle training, biofeedback training or rectal balloon training are recommended as second measures. Despite lack of ambiguity in the protocols used for pelvic rehabilitation and for patient selection, results seem effective as concerns intestinal function, anal continence and QoL [53]. If the previously outlined treatments in the MANUEL guidelines and the Boreal program have not yielded results, the recommended method is TAI. If symptoms persist following TAI, recommended approaches are sacral nerve neuromodulation (step 3), percutaneous endoscopic cecostomy and anterograde enema (step 4) and, as a final step, permanent colostomy (step 5) [41,51].
In our systematic review, the primary outcome was defined by the improvement in LARS, assessed by the LARS score, following RSPS.
Overall, three studies were RCTs [34,39,40], four were prospective studies and two were retrospective cohort studies [32,33,37,38], reporting pre- and post-treatment analysis of bowel function and QoL [35,36].
One study was assessed to be of excellent methodological quality [40], four to be of good methodological quality [32,34,37,39], three were of fair quality [33,35,38] and one was deemed to be of poor quality [36]. The primary method for gauging changes in bowel function and quality of life was through patient-reported outcome measures (PROMs).
In accordance with the inclusion criteria, all studies employed the LARS score as a PROM to assess bowel function. Six PROMs were also utilized to assess bowel function (MSKCC BFI: Memorial Sloan Kettering Cancer Center Bowel Function Instrument, CCIS: Cleveland Clinic Incontinence Score, VAS: visual analog scale, CCFFIS: Cleveland Clinic Florida Fecal Incontinence Score, FI score: fecal incontinence score, and ODS score: Obstructed Defecation Syndrome score), while four others measured QoL (FIQL score: Fecal Incontinence Quality of Life score, EQ-5D-5L™: 5-level EQ-5D version, EORTC QLQ-C30: European Organisation for Research and Treatment of Cancer Quality of Life questionnaire, SF-36 domain: Short-Form (36) Health Survey). This inconsistency in outcome measures hinders comparability. A consensus on the measures of bowel function and quality of life would ensure comparability in future research.
All the studies included in this systematic review (both comparative and non-comparative studies) showed an improvement in LARS-related symptoms, with a reduction in LARS score (which in most cases reached statistical significance). Furthermore, in six of the included studies, the mean/median value of the LARS score changed from the “major LARS” category to the “no LARS” category, while for the remaining three, the LARS score changed from the “major LARS” category to the “minor LARS” category. Therefore, these results seem to suggest the effectiveness of TAI in patients undergoing RSPS.
Our data appear to confirm the effectiveness of TAI in treating LARS following RSPS, as already shown in patients affected by neurological bowel dysfunction (NBD), both congenital or acquired or within functional conditions such as chronic constipation (CC) or fecal incontinence (FI) [54].
In our systematic review, among the comparative studies, three compared TAI with the standard of care [33,39,40] and one with PTNS treatment [34]. In all the comparative studies considered in this systematic review, a significant improvement in LARS score was observed in the TAI group compared to the control group. None of the control groups, whether receiving standard of care or PTNS, experienced a change in their LARS score category, all remaining in the “major LARS” category.
Enriquez-Navascues et al. compared TAI with PTNS, and both treatments were statistically significant in reducing the LARS score. In the TAI group, the average post-treatment LARS score value was 12 (IQR 12–26)—“no LARS”—while in the PTNS group, it was 30 (IQR 25–33)—“major LARS”—thus highlighting how clinical improvement occurred only in the TAI group.
Furthermore, EORTC QLQ-C30 improved in both groups. However, in the PTNS group, after six months of follow-up, a rapid worsening of symptoms was observed, accompanied by an increase in the LARS score, which was linked to a decline in quality of life. Currently, the study by Enriquez-Navascues et al. remains the only comparative study between TAI and PTNS. The results from Enriquez-Navascues et al.’s study suggest that TAI is more effective than PTNS in improving symptoms and quality of life. Based on these findings, the authors recommended restricting the use of PTNS to less severe and/or chronic forms of LARS [34]. A previous meta-analysis (with several study limitations) conducted by Liapis et al. evaluated the impact of PTNS on LARS, revealing improvements in both bowel function and quality of life [55]. In the study conducted by Meurette et al., as previously reported, a statistically significant improvement was observed at 3 months of follow-up in the LARS score among patients who underwent TAI compared to those who underwent SoC (p = 0.008) [39]. In the study conducted by Pieniowski et al., a statistically significant improvement was observed at 6 and 12 months of follow-up in the LARS score among patients who underwent TAI compared to those who underwent SoC (p < 0.0016 months/p = 0.002 12 months). Similarly, the EORTC QLQ-C30 results were in favor of the TAI group [40]. In the study conducted by McCutchan et al., a significant improvement in the LARS score was observed among patients who received TAI compared to those who received the SoC. These results suggest a clear advantage in efficacy, both in terms of symptom improvement and quality of life for TAI compared to SoC [33]. There is no information or comparisons available regarding the healthcare costs of the two procedures.
In terms of other bowel function PROMs, the secondary outcomes, seven studies have assessed intestinal function using scores other than the LARS score [32,33,34,36,38,39,40]. All studies consistently demonstrated a statistically significant improvement, except for Enriquez-Navascues et al. and Martellucci et al., who showed a non-significant improvement in ODS score and two items of the MSKCC BFI (discrimination between gas and stool; incontinence for flatus) [32,38].
Among studies included by our systematic review, six report questionnaires assessing the quality of life of patients undergoing TAI for LARS [32,34,37,38,39,40]. With the exception of Meurette with the EQ-5D-5L™ [39], all studies reporting quality of life questionnaires showed full or incomplete improvement following TAI.
Previous studies have not consistently demonstrated a link between an increase in LARS categories and a decline in QoL [20]. The improvement in both LARS and QoL scores highlights the effectiveness of TAI as a treatment for LARS after RSPS, improving both symptoms and quality of life.
At present, Rosen et al. are evaluating its prophylactic use immediately following ileostomy closure, with promising results [56].
Although our review moves in this direction, our results cannot be considered as universal.
In our review, the sample size of the studies was small (ranging from 13 to 117), the population sample was heterogeneous (the inclusion criteria were not uniform), and the number of patients undergoing neoadjuvant chemo-radiotherapy was not uniform.
The technique used for primary surgery (open, laparoscopic, robotic, transanal approaches) and the type of reconstruction (colorectal anastomosis, coloanal, with/without pouch) were heterogeneous and not reported in all the studies included in this systematic review, and this represents a limitation of the study itself. As previously mentioned [42,43], there are currently no recommendations in the literature supported by strong scientific evidence regarding the optimal surgical technique and type of reconstruction: R.T. J. Geitenbeek et al. conducted a meta-analysis where they highlighted no significant differences in patients’ urinary, sexual and fecal functioning and QoL scores across various TME techniques (open, laparoscopic (L-TME), robot-assisted (R-TME) and transanal total mesorectal excision (TaTME)) [57]. On the contrary, recent studies seem to suggest an advantage in total robotic mesorectal excision (rTME) compared to the transanal approach (taTME) and reconstruction with transverse coloplasty pouch (TCP) [58].
Moreover, the elapsed time between the primary surgery and the stoma reversal was not uniform. A 2021 meta-analysis by Vogel et al. showed that the risk of developing LARS with a defunctioning ileostomy was greater and that a prolonged time to ileostomy closure seems to reinforce the negative effect on bowel function [50]. On the contrary, in two recent publications, Yuhan Qi and Verkuijl, Sanne J. M.D, did not show a correlation between the presence of the defunctioning ileostomy and the negative reinforcement of a prolonged time of closure of the stoma with the severity of LARS [59,60]. Future research should be directed towards a better analysis of the various population subgroups, comparing the effects of the treatments for each type of subgroup.
Also, the types of devices used for TAI are different: eight studies use the Peristeen© rectal irrigation system, while Rodrigues et al. use a stoma irrigation device. The authors explain how this difference is due to the rejection of the Peristeen© systems by the Brazilian health regulatory agency and also due to the lower cost of the ostomy device.
Another factor that prevented us from disseminating our results is the presence of differences in patient follow-up periods. Despite this, our review’s results suggest that TAI has a beneficial effect on reducing the LARS score, both at short-term follow-up (3 months) and at short/medium-term follow-up (12 months). Although some authors suggest a stabilization of the LARS score after 1–2 years [61], the series of populations analyzed for a long follow-up period are limited [61,62,63].
The lack of uniformity in the various treatment protocols used reflects the absence of a standardized protocol validated in the literature during the period examined by the studies included in this review, highlighting the need for a consistent approach. The existence of a validated and uniform treatment protocol would facilitate the sharing of experiences among various research centers, particularly in addressing the diverse challenges that TAI poses to healthcare professionals and patients. Additionally, by standardizing data collection, studies would be less biased and qualitatively improved.
Our systematic review revealed a discontinuation rate ranging from 0% to 41%. The main causes of discontinuity reported by the studies examined in this systematic review were local recurrence or tumor progression, discomfort related to the procedure, the onset of adverse events, or treatment failure.
Based on the data extracted from the studies included in this systematic review, it was not possible to extrapolate a correlation between the type of protocol used and the dropout rate, although it can be assumed that improved pre-treatment education/training and ongoing support during treatment can significantly enhance adherence to TAI. In the literature, the primary reasons for abandoning TAI are related to side effects, therapeutic failure and the costs of materials, which not all healthcare systems provide for free. On the contrary, in some instances, discontinuity can lead to improved symptoms, making TAI no longer necessary. In the cohort examined in this systematic review, the discontinuity rate from TAI is comparable to that reported in the literature for patients with functional defecation disorders [64]. As previously suggested by Mekhael et al. [54], the high dropout rates of the studies included in this review suggest that TAI may not benefit all patients. To predict a positive outcome and guide the introduction of TAI to the most suitable patients, who could benefit from the treatment, it would be beneficial to investigate the predictors of interruption. Among the studies included in this review, the predictors of TAI discontinuation were not investigated. In agreement with Mekhael et al., this must be further explored in future studies.
The adverse event rate in the studies included in this systematic review showed an extremely wide range, from 0 to 93%. All reported adverse events were minor, with no intestinal perforations detected. The primary adverse events reported were bleeding, anal pain during irrigation and abdominal pain. The extreme variability in adverse events may be attributed to differences in study design and treatment protocols used across studies. Meurette et al., who reported a higher rate of serious adverse events (93%), conducted a multicenter study involving seven hospitals [39]. The treatment protocol in the study by Meurette et al. included patients 3 months after their primary surgery or stoma closure. The pre-treatment training and education period for the patient was not specified, while the average irrigation water volume of 718 mL (SD 135) was reported. Despite all centers being reported as experts in TAI, it is possible that education and training varied across centers. On the other hand, the study by Enriquez-Navascues et al., which did not report any adverse events, was a single-center study [34]. The treatment protocol involved at least 1 year of waiting after the primary surgery or stoma closure and at least 3–4 weeks of education and training with a dedicated and experienced nurse. However, the average volume of water used for irrigation was not reported. Despite these arguments, due to the small sample size and the heterogeneity of the protocols, it is not possible to establish a direct correlation between a specific protocol type and a higher or lower rate of adverse events. In a collection of adverse events caused by medical tools recorded by the European Community, United States Food and Drug Association (FDA) and other national qualified authorities, six perforations related to TAI were recorded (weighted average risk of a bowel perforation was six per million (1:167,000) irrigation procedures) [65], while standard perforation risk is 20 per million irrigation procedures (all irrigation systems) [66], 1:40,000 during flexible sigmoidoscopy [67], 1:1000 during colonoscopy [68] and 1:10,000 during barium enema procedures) [69]. To minimize adverse events, we believe it is crucial to offer TAI in specialized centers staffed by experienced healthcare professionals. These professionals can educate and train patients in the pre-treatment phase and provide ongoing support throughout the entire process.
The included studies have certain limitations. The follow-up periods varied between the studies, with the majority of them having a shorter duration. Additionally, the sample sizes of the included studies are generally small, potentially leading to type 2 errors. In most studies, external validation was generally considered to be of good quality. However, the small sample size may suggest a potential selection bias in patient recruitment. TAI is often combined with conservative modalities to optimize treatment; however, most studies fail to report concomitant treatment. This can lead to an overlapping effect between treatments, potentially confusing the specific outcomes for TAI. Future studies should explore the use and methods of combined treatments, aiming to improve quality. This systematic review has limitations, such as the potential risk of publication bias if studies investigating TAI that found no significant results were not published. Furthermore, few randomized controlled studies were identified and observational studies lacked propensity-score matching analysis. The integration of both comparative and non-comparative (single-arm) studies could lead to non-negligible increased bias. Such variability necessitates a cautious interpretation of the study outcomes. It highlights the importance of standardizing intervention protocols in future studies to minimize heterogeneity and enhance the comparability of results. This limitation also highlights the need for further research to expand this work, incorporating a larger number of studies and participants, standardizing treatment protocols and inclusion criteria and obtaining long-term results. This will enable a more definitive determination of TAI’s effectiveness in managing LARS.

5. Conclusions

All in all, LARS is a very frequent syndrome that is not adequately investigated and whose diagnosis rarely occurs in many centers. Thus, its incidence is destined to rise, increasing clinicians’ awareness and improving the accuracy of diagnostic tools. For this reason, the identification of safe and effective procedures will become increasingly important.
This review’s findings demonstrate that TAI improves bowel function and potentially enhances the quality of life for patients with LARS. Furthermore, in comparative studies, it has been shown to be more effective than SoC and PTNS in improving bowel function and quality of life. The discontinuation rate from TAI found in this review is moderately high, indicating the need for a personalized approach for each patient. It is crucial to refine patient selection and examine the factors that predict therapy dropout. It is also crucial to implement patient education and training by healthcare professionals with expertise in this field, aiming to improve adherence to treatment and reduce adverse events. It is highly recommended that future research be based on standardized treatment protocols and a large, homogeneous study sample.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/std13040033/s1, Table S1: Results of quality assessment of randomized and non-randomized studies with modified Downs and Black checklist.

Author Contributions

A.M.: conceptualization, methodology, validation, data curation, formal analysis, investigation, project administration, visualization, writing—original draft and writing—review and editing. M.Z. (Maurizio Zizzo): data curation, formal analysis, investigation, supervision, validation, writing—review and editing. M.Z. (Magda Zanelli), F.S., A.P., A.A. and C.B.: data curation, methodology. M.F.: supervision, writing—review and editing. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

The local ethics committee (Comitato Etico dell’Area Vasta Emilia Nord, Italy) ruled that no formal ethics approval was required in this study.

Informed Consent Statement

Not applicable.

Data Availability Statement

The data presented in this study are available on request from the corresponding author.

Acknowledgments

We thank Daniela Masi (Reggio Emilia Local Agency—IRCCS Advanced Technologies and Care Models in Oncology) for support in English editing. This study was partially supported by the Italian Ministry of Health—Ricerca Corrente Annual Program 2025.

Conflicts of Interest

The authors declare no conflicts of interest.

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Figure 1. PRISMA flowchart of literature search.
Figure 1. PRISMA flowchart of literature search.
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Table 1. Study characteristics.
Table 1. Study characteristics.
ReferenceCountryStudy PeriodStudy Design/CenterInclusion Criteria
Martellucci J, 2018 [32]ItalyApril 2015–May 2016Prospective/Single CenterAll patients undergoing low anterior resection for rectal cancer
McCutchan GM, 2018 [33]UKJanuary 2009–January 2014Prospective/Single CenterAll patients undergoing an anterior resection for rectal cancer who were aged 18 years or older and had restoration of bowel continuity for a minimum of 12 weeks
Enriquez-Navascues JM, 2020 [34]SpainMay 2017–February 2018RCT/
Multicenter		Patients had major LARS (score > 29) and at least 1 year had passed since they had had related surgery or closure of a protective ileostomy. All participants had undergone surgery for rectal cancer involving low anterior resection with total mesorectal excision and colorectal/coloanal anastomosis with curative intent
Dalsgaard P, 2021 [35]DenmarkJanuary 2012–January 2016Retrospective/Single Centern/a
Bianco F, 2022 [36]ItalyApril 2019–December 2021Retrospective/Single CenterAll patients who underwent TAI treatment after SHiP procedure for low rectal cancer reaching at least 3 months of follow-up
Rodrigues BDS, 2022 [37]BrazilJanuary 2003–December 2014Prospective/Single CenterAge > 18, absence of any disease other than rectal adenocarcinoma, presence of anastomosis, absence of local recurrence, more than 1 year after diverting stoma closure, availability of running water or minimal sanitary conditions
Falletto E, 2023 [38]Italyn/aProspective/MulticenterAge over 18 years; prescribed to use TAI as part of the normal clinical practice; not previously treated with TAI; trained to handle the irrigation system by healthcare professionals
Meurette G, 2023 [39]Switzerland/FranceJanuary 2020–December 2021RCT/MulticenterPatients with a low colorectal or coloanal anastomosis who had major LARS (LARS score at least 30) at least 3 months after stoma closure
Pieniowski EHA, 2023 [40]SwedenMay 2016–November 2019RCT/MulticenterPatients who had undergone rectal cancer surgery with total mesorectal excision (TME) and a defunctioning ileostomy, >6 months since stoma reversal, normal endoscopic examination of the anastomosis at 1-year follow-up visit and with an understanding of the Swedish language
TAI: transanal irrigation, LARS: low anterior resection syndrome, RCT: randomized controlled trial, SoC: standard of care, PTNS: posterior tibial nerve stimulation, n/a: not available, SHiP: short stump and high anastomosis pull-through.
Table 2. Population characteristics.
Table 2. Population characteristics.
ReferenceSample of
TAI Cohort for LARS Syndrome		Sample of
Comparative Cohort/Type of Treatment		TAI CohortNeoadiuvat Chemo-RadiotherapyFollow-Up Time (Months)
Gender (M/F)Age (Years)
Martellucci J, 2018 [32]27 (33)-17/1061 (range 29–83)189
McCutchan GM, 2018 [33]156/
SoC		14/165 (range 36–79)6/5 1 6
Enriquez-Navascues JM, 2020 [34]1313/
PTNS		9/468 (range 48–71)76
Dalsgaard P, 2021 [35]17-n/an/an/an/a
Bianco F, 2022 [36]13-9/467 ± 6 (range 54–79)n/aMean 9 (range 3–21, SD ± 5.02)
Rodrigues BDS, 2022 [37]22-16/658.59 ± 12.02 (median)1612
Falletto E, 2023 [38]117-n/an/an/a6
Meurette G, 2023 [39]1515/
SoC		13/263.3 (range 37–81)11 23
Pieniowski EHA, 2023 [40]2216/
SoC		11/1165 (mean)7/16 312
TAI: transanal irrigation, LARS: low anterior resection syndrome, RCT: randomized controlled trial, SoC: standard of care, PTNS: posterior tibial nerve stimulation, n/a: not available, SHiP: short stump and high anastomosis pull-through. 1 Six patients with neo-adjuvant chemotherapy; five patients with preoperative radiotherapy; 2 eleven patients with preoperative radiotherapy; 3 seven patients with neo-adjuvant chemotherapy; sixteen patients with preoperative radiotherapy.
Table 3. Outcomes of TAI cohort patients.
Table 3. Outcomes of TAI cohort patients.
ReferenceType of TAITAI ProcedureLARS Score
Pre-TAI/Post-TAI		Bowel Function Outcome
Pre-TAI/Post-TAI		QoL OutcomeDiscontinuationAdverse Events
Martellucci J, 2018 [32]Peristeen© system (Coloplast,
Humblebaek, Denmark)		Irrigation on alternate days (3 or 4 times per week) over the course of 6 months. After 6 months: a 266 mL enema (2 Clisma fleet; Recordati Spa, Milan, Italy) administered according to the same schedule (3–4 times per week on alternate days) for 3 months35.1 (30–42)/12.2 (0–21) (p < 0.001)
Median (range)		MSKCC BFI: significant mprovement in: Q4, 5, 6, 8, 9, 10, 15, 17, 18 and a non-significant improvement in dietary items, discrimination between gas and stool, and incontinence for flatusSF-36 domain: improved mental health, social functioning, emotional role functioning and bodily pain, and a non-significant improvement in vitality, physical functioning, general health perceptions and physical role functioning6 (18.2%)n/a
McCutchan GM, 2018 [33]Peristeen© Rectal irrigation systems (Coloplast, Peterborough, UK)n/a35.93 (21–42)/17.73 (0–41)
mean (range)		St Marks score:
9.73 (2–15)/3.20 (0–9)
mean (range)		-00
Enriquez-Navascues JM, 2020 [34]Peristeen© system (Coloplast,
Humlebaek, Denmark)		After specific education, the irrigation procedures,
using volumes of water were adjusted for each patient, were
initially carried out once a day and then three to four times
a week for a period of up to 6 months		35 (32–39)/12 (12–26) (p = 0.021)
Median (IQR)		FI score (Vaizey):
15 (11–18)/6 (4–7) (p = 0.037)
ODS score (Altomare):
10 (7–14)/8 (6–9) (p = 0.083)
(IQR)		EORTC QLQ-C30
Global health status: 8 (8–9)/12 (9–12)
Physical functioning: 35 (28–43)/28 (26–34)
Role functioning: 8 (7–8)/7 (7–7)
VAS: 2 (0–3)/7.5 (6–9)
(IQR)		3 (23.1%)0
Dalsgaard P, 2021 [35]n/an/a39 (35–41)/28 (13–36) (p = 0.006)
Median (IQR)		--7 (41.2%)n/a
Bianco F, 2022 [36]Peristeen system
® (Coloplast,
Humlebaek, Denmark)		Every day for the first 5 days
and then every other day for 2 weeks		36 (8)/3 (3)
Median (IQR)		CCIS
13 (6)/2 (4)
Median (IQR)		-4 (31%)2
Rodrigues BDS, 2022 [37]Ostomy irrigation system (Coloplast, São Paulo, SP, Brazil)n/a39 (4)/8 (9)
Median (IQR)		-SF-36 domain: improved vitality (p = 0.025), physical (p = 0.002), social (p = 0.001), and emotional aspects (p = 0.001)2 (9.1%)n/a
Falletto E, 2023 [38]Peristeen
® Plus irrigation system		n/a34.48 ± 9.70, 37.00 (34.00–41.00)/
17.47 ± 11.26, 18.00 (7.00–27.00) (p < 0.0001)
Mean ± standard deviation, median (25th–75th percentile)		VAS scale
2.66 ± 1.90, 2.00 (2.00–3.00)/7.18 ± 1.91, 8.00 (7.00–8.00)
mean ± standard deviation; median (25th–75th percentile)		-11 (9.4%)n/a
Meurette G, 2023 [39]Peristeen© cone catheter (Coloplast, Humlebaek, Denmark)After specific education and
training, irrigations were administered by the patient
daily, starting with a maximum one-litre enema, with a
self-reported diary being used to record daily irrigation
efficacy		37.4 (35.5, 39.2)/21.3 (14.7, 27.8)
mean (95% CI)		CCFFIS: 17.9/12.2 (9.6, 14.8)
mean (95% CI)		FIQL score:
Lifestyle: 2.19/3.1 (2.65, 3.55)
Coping/behaviour: 1.94/2.95 (2.55, 3.35)
Depression/self-perception: 3.47/3.41 (2.87, 3.95)
Embarrassment: 2.29/2.98 (2.57, 3.38)
EQ-5D-5L™
Utility score: 0.88/0.92 (0.86, 0.97)
VAS score: 75.8/82.8 (70.2, 95.5)
mean (95% CI)		017
Pieniowski EHA, 2023 [40]Peristeen© System (Coloplast Group, Humlebaek, Denmark) After education, a test irrigation. At home: irrigated
daily for 2 weeks, initially with 500 mL water, which gradually
could be increased to a maximum of 1000 mL		36.4/22.9
mean score		CCFFIS: 9.6/6.4
mean score		EORTC QLQ-C30
Global health status: 8 (8–9)/12 (9–12)
Physical functioning: 35 (28–43)/28 (26–34)
Role functioning: 8 (7–8)/7 (7–7)
VAS: 2 (0–3)/7.5 (6–9)
Difference in mean score
(95% CI)		6 (27%)0
TAI: transanal irrigation, LARS: low anterior resection syndrome, QoL: quality of life, n/a: not available, IQR: interquartile range, MSKCC BFI: Memorial Sloan Kettering Cancer Center Bowel Function Instrument, CCIS: Cleveland Clinic Incontinence Score, VAS: visual analog scale, CCFFIS: Cleveland Clinic Florida Fecal Incontinence Score, FI score: fecal incontinence score, ODS score: Obstructed Defecation Syndrome score; FIQL score: Fecal Incontinence Quality of Life score, EQ-5D-5L™: 5-level EQ-5D version, EORTC QLQ-C30: European Organisation for Research and Treatment of Cancer Quality of Life questionnaire, SF-36 domain: Short-Form (36) Health Survey.
Table 4. Comparisons between pre-treatment and post-treatment LARS score among comparative studies.
Table 4. Comparisons between pre-treatment and post-treatment LARS score among comparative studies.
Reference LARS Score
Sample of
TAI Cohort		Pre-TreatmentPost-Treatmentp-Value
McCutchan GM, 2018 [33]TAI1535.93 (21–42)
mean (range)		17.73 (0–41)n/a
Soc634.17 (32–37)32.35 (26–37)
Enriquez-Navascues JM, 2020 [34]TAI1035 (IQR 32–39)12 (IQR 12–26)0.021
PTNS1335 (IQR 34–37)30 (IQR 25–33)0.045
Meurette G, 2023 [39]TAI1537.4 (35.5, 39.2)
mean (95% CI)		21.3 (14.7, 27.8)0.008
SoC1539.2 (37.5, 40.9)32.2 (27.3, 37.1)
Pieniowski EHA, 2023 [40]TAI2236.4
mean score		22.9n/a 1
SoC1635.632.4
TAI: transanal irrigation, LARS: low anterior resection syndrome, n/a: not available, SoC: standard of care, PTNS: posterior tibial nerve stimulation, IQR: interquartile range. 1 Difference in mean score (95% CI) at 12 months of follow-up between TAI group and SoC group: −9.5 (−15.2 to −3.7) (statistically significant).
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MDPI and ACS Style

Morini, A.; Fabozzi, M.; Zanelli, M.; Sanguedolce, F.; Palicelli, A.; Annicchiarico, A.; Bonelli, C.; Zizzo, M. Transanal Irrigation in Patients with Low Anterior Resection Syndrome After Rectal-Sphincter-Preserving Surgery for Oncological and Non-Oncological Disease: A Systematic Review. Surg. Tech. Dev. 2024, 13, 409-425. https://doi.org/10.3390/std13040033

AMA Style

Morini A, Fabozzi M, Zanelli M, Sanguedolce F, Palicelli A, Annicchiarico A, Bonelli C, Zizzo M. Transanal Irrigation in Patients with Low Anterior Resection Syndrome After Rectal-Sphincter-Preserving Surgery for Oncological and Non-Oncological Disease: A Systematic Review. Surgical Techniques Development. 2024; 13(4):409-425. https://doi.org/10.3390/std13040033

Chicago/Turabian Style

Morini, Andrea, Massimiliano Fabozzi, Magda Zanelli, Francesca Sanguedolce, Andrea Palicelli, Alfredo Annicchiarico, Candida Bonelli, and Maurizio Zizzo. 2024. "Transanal Irrigation in Patients with Low Anterior Resection Syndrome After Rectal-Sphincter-Preserving Surgery for Oncological and Non-Oncological Disease: A Systematic Review" Surgical Techniques Development 13, no. 4: 409-425. https://doi.org/10.3390/std13040033

APA Style

Morini, A., Fabozzi, M., Zanelli, M., Sanguedolce, F., Palicelli, A., Annicchiarico, A., Bonelli, C., & Zizzo, M. (2024). Transanal Irrigation in Patients with Low Anterior Resection Syndrome After Rectal-Sphincter-Preserving Surgery for Oncological and Non-Oncological Disease: A Systematic Review. Surgical Techniques Development, 13(4), 409-425. https://doi.org/10.3390/std13040033

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