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Article

Low Anterior Resection Syndrome (LARS) after Surgery for Rectal Cancer: An Inevitable Price to Pay for Survival, or a Preventable Complication?

by
Edoardo Maria Muttillo
1,*,†,
Alice La Franca
1,†,
Alessandro Coppola
2,
Francesco Saverio Li Causi
1,
Marzia Checchelani
1,
Alice Ceccacci
1,
Giorgio Castagnola
1,
Giovanni Maria Garbarino
3,
Mattia Falchetto Osti
4,
Genoveffa Balducci
1 and
Paolo Mercantini
1
1
Department of Medical Surgical Science and Translational Medicine, Sant’Andrea Hospital, Sapienza University of Rome, 00191 Rome, Italy
2
Department of Surgery, Sapienza University of Rome, Viale Regina Elena 291, 00161 Rome, Italy
3
Department of General Surgery, Sant’Eugenio Hospital, 00144 Rome, Italy
4
Radiotherapy Oncology, Sant’Andrea Hospital, Sapienza University of Rome, 00191 Rome, Italy
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
J. Clin. Med. 2023, 12(18), 5962; https://doi.org/10.3390/jcm12185962
Submission received: 25 August 2023 / Revised: 7 September 2023 / Accepted: 12 September 2023 / Published: 14 September 2023
(This article belongs to the Section General Surgery)
Browse Figures
Versions Notes

Abstract

:
Background: Rectal cancer is frequent and often treated with sphincter-saving procedures that may cause LARS, a syndrome characterized by symptoms of bowel disfunction that may severely affect quality of life. LARS is common, but its pathogenesis is mostly unknown. The aim of this study is to assess the incidence of LARS and to identify potential risk factors. Methods: We performed an observational retrospective single center analysis. The following data were collected and analyzed for each patient: demographics, tumor-related data, and intra- and peri-operative data. Statistical analysis was conducted, including descriptive statistics and multivariate logistic regression to identify independent risk factors. Results: Total LARS incidence was 31%. Statistically significant differences were found in tumor distance from anal verge, tumor extension (pT and diameter) and tumor grading (G). Multivariate analysis identified tumor distance from anal verge and tumor extension as an independent predictive factor for both major and total LARS. Adjuvant therapy, although not significant at univariate analysis, was identified as an independent predictive factor. Time to stoma closure within 10 weeks seems to reduce incidence of major LARS. Conclusions:bold LARS affects a considerable portion of patients. This study identified potential predictive factors that could be useful to identify high risk patients for LARS.

Graphical Abstract

1. Introduction

Colorectal cancer is the third most commonly diagnosed cancer in the world, and the second most common cause of cancer death [1]. Total mesorectal excision (TME) and neoadjuvant radiotherapy are considered the cornerstones of treatment for potentially curable rectal cancer, and their introduction has radically improved oncological outcomes, both in terms of increased survival and reduction in permanent stoma rates [2,3]. Although surgical treatment has significantly improved, patients who undergo a sphincter-saving procedure may experience symptoms and consequences of bowel dysfunction that can severely affect their quality of life [4,5]. These symptoms include variable and unpredictable bowel function, altered stool consistency or frequency, repeated painful evacuations, emptying difficulties, urgency, incontinence, and soiling [6]. The term low anterior resection syndrome (LARS) has been adopted to refer to this syndrome [4]; however, its definition has only recently been standardized based on international consensus [6]. LARS is consistently linked to a decrease in the quality of life. As access to treatment for rectal cancer improves, LARS increasingly becomes a significant burden of disease [7]. Surgical trauma to the anal sphincter complex, colonic denervation, reduced rectal capacity and compliance, radiotherapy-induced fibrosis, fecal diversion and, more recently, also altered colonic mobility, have been identified as potential risk factors for LARS [8]; however, their exact role is unknown. The development of a validated patient-reported outcome measure (LARS score) has improved the standardization of reporting and prevalence of LARS defined using this score is reported to be 41% (95% CI, 34–48%) [9]. The aim of this study is to assess the incidence of LARS according to LARS scores in patients who underwent sphincter-saving resection in our center, and to identify possible predictive factors.

2. Materials and Methods

We performed an observational retrospective single center analysis.
Patients who underwent Low Anterior Resection (LAR) for cancer at the General Surgery Department at Sant’Andrea Hospital in Rome from January 2013 to June 2022 were selected. Exclusion criteria were age < 18 years, LAR for benign diseases, follow up <12 months, permanent ostomy, other evident causes of fecal incontinence (for instance, advanced dementia) and death. Out of the 351 patients initially considered, 147 were excluded due to not meeting the inclusion criteria, 123 could not be located, and 3 declined to participate. Ultimately, a total of 78 patients were chosen for the analysis (Figure 1).
The following data were collected and analyzed for each patient: demographics (age, sex), tumor-related data (TNM stage, distance from anal verge, grading), and intra- and perioperative data (American Society of Anesthesiologists (ASA) score, surgical technique, operative time, ileostomy, time to stoma closure, neoadjuvant and/or adjuvant therapy, morbidity according to Clavien-Dindo score) [10].
Among the 78 patients, 30 females and 48 males, median age was 65 years (range 57–73). The entire population underwent low anterior resection with anastomosis and protective ileostomy was performed in 34% of cases. The distance of the tumor from the anal verge was ≥10 cm in 49%, between 5 and 10 cm in 38% and ≤5 cm in 13%.

2.1. Statistical Analysis

Continuous variables are presented as median and interquartile range (IQR), while categorical variables are expressed as units and percentages. Descriptive statistics were used to summarize information relevant to the study. The differences between groups were analyzed using Wilcoxon rank sum test for continuous variables, and Pearson’s Chi-squared test or Fisher’s exact test, as appropriate, for categorical variables. A multivariate binomial logistic regression was developed to identify independent predictors of outcomes. Significance was accepted at p < 0.05. All statistical analyses were performed using R (version 4.3.1; R Foundation for Statistical Computing, Vienna, Austria).

2.2. LARS Score

Each patient was reached telephonically and subjected to LARS questionnaire, consisting of five questions as shown in Figure 2. The allocated points per question were added together to give a final LARS score between 0 and 42. Finally, the population was divided into three categories [9]:
  • No LARS (L0): 0–20;
  • Minor LARS (mL): 21–29;
  • Major LARS (ML): 30–42.

3. Results

In the examined population, 30 patients (38%) were females and 48 (62%) were males, with a median age of 65 years (IQR 57, 73). A total of 28 patients (36%) had an American Society of Anesthesiologists score > 2.
The distance of the tumor from the anal verge was ≥10 cm in 38 patients (49%) and between 5 and 10 cm in 30 patients (38%). Ten patients (13%) underwent ultra-low resection for a tumor localized at ≤5 cm from the anal verge (Table 1).
Each patient underwent LAR with anastomosis, 53 (68%) with open approach and 25 (32%) with laparoscopic approach. Median operative time was 210 min (IQR 180, 248). Ostomy formation was performed on a total of 29 patients, which accounts for 37% of the study’s participants. Protective temporary ileostomy was performed in 27 cases, while in two patients, a salvage ileostomy was created due to anastomotic leak. Finally, 49 patients (63%) were discharged without ileostomy.
Moreover, in 14 cases (17.95%), other intraoperative procedures were associated (two single liver metastasectomies, one splenectomy, one colostomy reversal, three ovariectomies, one hysterectomy with bilateral ovariectomy, one ureteral stent for intraoperative damage, three cholecystectomies, one umbilical hernia repair).
The overall complication rate was 17% (12 patients), with 7 grade I-II and 1 grade IIIa according to Clavien-Dindo classification [10]. A total of four patients underwent emergency surgery, two for anastomotic leak, one for a fistula and one for rectal bleeding (grade IIIb).
A total of 28 patients (36%) underwent neoadjuvant radiotherapy, 24 (86%) with long-course protocol and four (14%) with short-course protocol. Finally, eight patients (10%) underwent adjuvant therapy (Table 2).
The total LARS (TL) rate was 31% (n = 24), with 17% of patients (n = 13) manifesting the symptoms of minor LARS and 14% (n = 11) of major LARS.
By univariate analysis, the following predictive factors for LARS were found to be statistically significant: tumor distance from anal verge (p = 0.041), tumor extension considered both as tumor diameter (p = 0.013) and pathological T stage (p = 0.007).
Finally, a significant difference in tumor grading (G) was present in patients with ML compared to no LARS (p = 0.038) (Table 3).
Multivariate analysis confirmed the role of tumor distance from anal verge as an independent predictive factor for both ML and TL (p = 0.006), with tumors located at 5–10 cm presenting the highest risk of LARS development (OR 5.58). Tumor extension, both in terms of diameter and T stage, was also found to be an independent predictive factor for both minor and total LARS (p = 0.015). Finally, although not significant at univariate analysis, adjuvant therapy was identified as an independent predictive factor for minor, major and total LARS (p = 0.004) (Table 4).

4. Discussion

Patients who underwent low anterior resection with TME, which remains the gold standard treatment for rectal cancer [11,12], can develop a functional anorectal alteration known as low anterior resection syndrome.
Bearing in mind the strong negative impact on patients’ quality of life, the aim of this study was to calculate incidence of major and minor LARS, and to identify possible predictive factors.
Our results showed a TL rate of 31% (26/78 patients), with a 14% rate of major LARS, which seems far below values reported in literature that can reach up to 40% for ML and 65% for TL [13].
In this study, the following factors emerged as predictive for the development of LARS: tumor size (T stage), adjuvant therapy and distance from the anal verge.
Increased tumor size in itself, calculated in centimeters, did not translate into increased rates of LARS, but tumor size as pT stage showed an impact on LARS. While, as might be expected, as pT increased, so did the risk of developing TL (p = 0.015) and mL (p = 0.003); a surprising finding was the increase in TL shown in the pT2 group (OR 9.05) compared to pT3 (OR 0.91). In the opinion of this research group, though, this finding can be attributed to the nonnegligible fraction within the pT2 group of patients downstaged following neoadjuvant therapy which, although not found to be significant on our series, is recognized in the literature as a risk factor for LARS [9,14,15,16,17,18,19].
Li et al. conducted a meta-analysis in 2022, including 33 studies and involving 17,917 patients. The study concluded that neoadjuvant therapy emerged as an independent risk factor for the significant development of major LARS, with an odds ratio of 3.09 (p < 0.001) [20].
Similar results were obtained by Rui Sun et al. in 2021 [21]; total incidence of ML was 44% and long course neoadjuvant radiotherapy has shown OR 2.89 (p < 0.01).
This role of oncological therapy on the development of LARS in our series was confirmed by analysis of the adjuvant therapy effect. In fact, a combination of adjuvant chemotherapy and radiotherapy has been shown to be a risk factor for all subgroups (total, minor and major LARS).
In the univariate analysis, tumor grading played a significant role, revealing that patients with less differentiated tumors were more prone to experiencing major LARS development (38% of ML among G3 tumors versus 0% G0-G1 and 5.9% G2).
However, on multivariate analysis, the significance was lost probably because the role of grading is to be regarded more as a non-independent risk factor (as lower differentiation is often related to more aggressive tumors and may be associated with larger size and more advanced stages more likely to require oncological therapies; all of which are risk factors for LARS, as we have already discussed).
A distance from anal verge of between 10 and 15 cm was confirmed as protective factor for development of TL (OR 0.19) and ML (OR 0.46), in accordance with global literature [22,23]. Interestingly, we found high rate of TL (40%, OR 5.58) and ML (31%, OR >1000) in patients with tumors of medium rectum (between 5 and 10 cm), probably due to the closeness of this area to the hypogastric plexus nerve that can be damaged during surgery [24]. Sturiale et al., in a retrospective analysis published in 2017 including 93 patients, had similar results [19].
In this scenario, transanal TME (TaTME), which has its primary indication in the middle rectum cancer, could play a role, although the literature at the moment has not shown a difference in LARS rates between TaTME and laparoscopic TME [25].
As for the last factor considered, the presence of ileostomy was associated with a higher rate of both total LARS (41% vs. 24%) and major LARS (29% vs. 9.8%). However, these findings have shown a trend that is not statistically significant (p = 0.12 for TL and p = 0.08 for ML), probably due to the small sample size under study.
Other interesting data are the analysis of interval of time to stoma closure, which showed that patients with late stoma closure are more likely to develop LARS (medians to stoma closure: 43 weeks for LARS patients versus 19 weeks for no LARS group) and major LARS (39 weeks for ML group versus 19 for no LARS group). As shown in Figure 3, the best time for stoma closure appears to be within 10 weeks, even though this finding certainly needs to be validated by subsequent studies (p = 0.11) on a larger patient sample.
Therefore, the risk of developing LARS in patients undergoing anterior rectal resection for cancer may depend on nonmodifiable, partially modifiable, and modifiable factors. The non-modifiable factors are tumor-related: distance from the anal margin < 10 cm, larger dimension of the tumor (≥pT2) and low degree of differentiation (G3) (with the latter two factors probably related to each other). Thus, the goal must be to identify these patients to properly stratify risk and subject them to close functional follow-up. In this light, Yan et al. have developed a nomogram to stratify patients according to the risk of developing LARS that will require further data to be validated but may be a good starting point [26].
On the other hand, factors that can only be partially modified are those that involve treatment choices with an impact on survival: adjuvant therapy and ileostomy.
On this last point, in this study group’s opinion, correct indication remains fundamental. Although the literature has often focused on the burden of ileostomy in terms of quality of life and psychological impact on patients, it now appears necessary to start asking how much temporary bowel defunctionalization that derives from ileostomy exposes patients to the risk of developing functional alterations that persist even when the ostomy is closed. Indeed, if we examine the fact that ostomy seems to not act as a protective factor for anastomotic leak [27,28,29], but has to be considered a safety device in patients with anastomotic leak [30], the excess of ostomies performed becomes evident.
The main fully modifiable factor that was the object of our study, however, was the time of ileostomy closure. An early closure seems to reduce the rate of patients developing total LARS and major LARS, and this finding seems to be confirmed by the few existing studies in the literature [14,31].
Finally, to compare our findings with those presented in the literature, Parnasa et al. [32] published a retrospective single-center study of 240 patients in 2022, obtaining results similar to ours: a smaller distance from the anal verge, neoadjuvant radiotherapy and TME (versus partial mesorectal excision and, therefore, a more conservative approach on the hypogastric nerves) resulted as independent prognostic factors for LARS. He et al. in 2022 [33] conducted a post hoc analysis on 327 patients subjected to chemotherapy followed by sphincter-saving proctectomy. Long-course neoadjuvant radiation, height of anastomosis and anastomotic leak (not analyzed by our study) were reported as predictive factors for the development of ML.
On the other hand, data pertaining to early ileostomy closure are still poor and controversial, and need further validation.
This study has several limitations: first, the small sample size (resulting from the notable number of patients found to be untraceable). Second, the LARS score is, by definition, based on the symptomatology reported by patients and, therefore, does not allow excluding other causes of incontinence and functional intestinal disorders. Finally, the retrospective nature of the study requires the need to confirm the results obtained in the context of a prospective study.

5. Conclusions

While patients who undergo surgery for rectal cancer often achieve favorable survival outcomes, it is important to acknowledge that the impact on their quality of life remains significant. Specifically, low anterior resection syndrome affects a considerable portion of patients. Within our series, the incidence of LARS was noted to be 31%. This study further pinpointed potential predictive factors. Among these, certain factors are modifiable, such as the closure of ileostomies within a 10-week timeframe. Additionally, there are non-modifiable factors (such as distance from the anal margin, pT stage, and adjuvant therapy) that play a crucial role in identifying patients at risk of LARS development. This recognition is essential for guiding these patients toward more focused functional follow-up, ultimately enhancing their overall care.

Author Contributions

Conceptualization: E.M.M. and A.L.F.; methodology: E.M.M., A.L.F., G.B., P.M. and F.S.L.C.; formal analysis: E.M.M., A.L.F., A.C. (Alice Ceccacci) and F.S.L.C.; data curation: A.L.F., M.C., M.F.O., A.C. (Alice Ceccacci) and A.C. (Alessandro Coppola); writing—original draft preparation E.M.M., A.L.F., G.B., P.M., A.C. (Alice Ceccacci), A.C. (Alessandro Coppola) and F.S.L.C.; writing—review and editing A.C. (Alessandro Coppola), G.M.G., G.C., M.F.O., G.B. and P.M. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not required.

Informed Consent Statement

No patient consent was necessary due to the type of the study.

Data Availability Statement

Referring to corresponding author.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J. Clin. 2021, 71, 209–249. [Google Scholar] [CrossRef] [PubMed]
  2. Heald, R.J.; Ryall, R.D. Recurrence and Survival after Total Mesorectal Excision for Rectal Cancer. Lancet 1986, 1, 1479–1482. [Google Scholar] [CrossRef] [PubMed]
  3. van Gijn, W.; Marijnen, C.A.M.; Nagtegaal, I.D.; Kranenbarg, E.M.-K.; Putter, H.; Wiggers, T.; Rutten, H.J.T.; Påhlman, L.; Glimelius, B.; van de Velde, C.J.H.; et al. Preoperative Radiotherapy Combined with Total Mesorectal Excision for Resectable Rectal Cancer: 12-Year Follow-up of the Multicentre, Randomised Controlled TME Trial. Lancet Oncol. 2011, 12, 575–582. [Google Scholar] [CrossRef] [PubMed]
  4. Bryant, C.L.C.; Lunniss, P.J.; Knowles, C.H.; Thaha, M.A.; Chan, C.L.H. Anterior Resection Syndrome. Lancet Oncol. 2012, 13, e403–e408. [Google Scholar] [CrossRef]
  5. Keane, C.; Wells, C.; O’Grady, G.; Bissett, I.P. Defining Low Anterior Resection Syndrome: A Systematic Review of the Literature. Color. Dis. 2017, 19, 713–722. [Google Scholar] [CrossRef]
  6. Keane, C.; Fearnhead, N.S.; Bordeianou, L.G.; Christensen, P.; Basany, E.E.; Laurberg, S.; Mellgren, A.; Messick, C.; Orangio, G.R.; Verjee, A.; et al. International Consensus Definition of Low Anterior Resection Syndrome. Color. Dis. 2020, 63, 274–284. [Google Scholar] [CrossRef]
  7. Denlinger, C.S.; Barsevick, A.M. The Challenges of Colorectal Cancer Survivorship. J. Natl. Compr. Cancer Netw. JNCCN 2009, 7, 883–893; quiz 894. [Google Scholar] [CrossRef]
  8. Varghese, C.; Wells, C.I.; Bissett, I.P.; O’Grady, G.; Keane, C. The Role of Colonic Motility in Low Anterior Resection Syndrome. Front. Oncol. 2022, 12, 975386. [Google Scholar] [CrossRef]
  9. Emmertsen, K.J.; 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, 922–928. [Google Scholar] [CrossRef]
  10. Clavien, P.A.; Barkun, J.; De Oliveira, M.L.; Vauthey, J.N.; Dindo, D.; Schulick, R.D.; De Santibañes, E.; Pekolj, J.; Slankamenac, K.; Bassi, C.; et al. The Clavien-Dindo Classification of Surgical Complications: Five-Year Experience. Ann. Surg. 2009, 250, 187–196. [Google Scholar] [CrossRef]
  11. Benson, A.B.; Venook, A.P.; Al-Hawary, M.M.; Arain, M.A.; Chen, Y.-J.; Ciombor, K.K.; Cohen, S.; Cooper, H.S.; Deming, D.; Garrido-Laguna, I.; et al. NCCN Guidelines Insights: Rectal Cancer, Version 6.2020: Featured Updates to the NCCN Guidelines. J. Natl. Compr. Cancer Netw. 2020, 18, 806–815. [Google Scholar] [CrossRef]
  12. Glynne-Jones, R.; Wyrwicz, L.; Tiret, E.; Brown, G.; Rödel, C.; Cervantes, A.; Arnold, D. Rectal Cancer: ESMO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-Up. Ann. Oncol. 2017, 28, iv22–iv40. [Google Scholar] [CrossRef]
  13. Croese, A.D.; Lonie, J.M.; Trollope, A.F.; Vangaveti, V.N.; Ho, Y.-H. A Meta-Analysis of the Prevalence of Low Anterior Resection Syndrome and Systematic Review of Risk Factors. Int. J. Surg. 2018, 56, 234–241. [Google Scholar] [CrossRef] [PubMed]
  14. Hughes, D.L.; Cornish, J.; Morris, C.; on behalf of the LARRIS Trial Management Group. Functional Outcome following Rectal Surgery—Predisposing Factors for Low Anterior Resection Syndrome. Int. J. Color. Dis. 2017, 32, 691–697. [Google Scholar] [CrossRef] [PubMed]
  15. Ekkarat, P.; Boonpipattanapong, T.; Tantiphlachiva, K.; Sangkhathat, S. Factors Determining Low Anterior Resection Syndrome after Rectal Cancer Resection: A Study in Thai Patients. Asian J. Surg. 2016, 39, 225–231. [Google Scholar] [CrossRef] [PubMed]
  16. Bondeven, P.; Emmertsen, K.J.; Laurberg, S.; Pedersen, B.G. Neoadjuvant Therapy Abolishes the Functional Benefits of a Larger Rectal Remnant, as Measured by Magnetic Resonance Imaging after Restorative Rectal Cancer Surgery. Eur. J. Surg. Oncol. EJSO 2015, 41, 1493–1499. [Google Scholar] [CrossRef] [PubMed]
  17. Hain, E.; Manceau, G.; Maggiori, L.; Mongin, C.; Prost À La Denise, J.; Panis, Y. Bowel Dysfunction after Anastomotic Leakage in Laparoscopic Sphincter-Saving Operative Intervention for Rectal Cancer: A Case-Matched Study in 46 Patients Using the Low Anterior Resection Score. Surgery 2017, 161, 1028–1039. [Google Scholar] [CrossRef]
  18. Carrillo, A.; Enríquez-Navascués, J.M.; Rodríguez, A.; Placer, C.; Múgica, J.A.; Saralegui, Y.; Timoteo, A.; Borda, N. Incidencia y caracterización del síndrome de resección anterior de recto mediante la utilización de la escala LARS (low anterior resection score). Cir. Esp. 2016, 94, 137–143. [Google Scholar] [CrossRef]
  19. Sturiale, A.; Martellucci, J.; Zurli, L.; Vaccaro, C.; Brusciano, L.; Limongelli, P.; Docimo, L.; Valeri, A. Long-Term Functional Follow-up after Anterior Rectal Resection for Cancer. Int. J. Color. Dis. 2017, 32, 83–88. [Google Scholar] [CrossRef]
  20. Li, X.; Fu, R.; Ni, H.; Du, N.; Wei, M.; Zhang, M.; Shi, Y.; He, Y.; Du, L. Effect of Neoadjuvant Therapy on the Functional Outcome of Patients with Rectal Cancer: A Systematic Review and Meta-Analysis. Clin. Oncol. 2023, 35, e121–e134. [Google Scholar] [CrossRef]
  21. 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, 7249–7258. [Google Scholar] [CrossRef] [PubMed]
  22. Ye, L.; Huang, M.; Huang, Y.; Yu, K.; Wang, X. Risk Factors of Postoperative Low Anterior Resection Syndrome for Colorectal Cancer: A Meta-Analysis. Asian J. Surg. 2022, 45, 39–50. [Google Scholar] [CrossRef] [PubMed]
  23. Nicotera, A.; Falletto, E.; Arezzo, A.; Mistrangelo, M.; Passera, R.; Morino, M. Risk Factors for Low Anterior Resection Syndrome (LARS) in Patients Undergoing Laparoscopic Surgery for Rectal Cancer. Surg. Endosc. 2022, 36, 6059–6066. [Google Scholar] [CrossRef] [PubMed]
  24. Kauff, D.W.; Koch, K.P.; Somerlik, K.H.; Heimann, A.; Hoffmann, K.P.; Lang, H.; Kneist, W. Online Signal Processing of Internal Anal Sphincter Activity during Pelvic Autonomic Nerve Stimulation: A New Method to Improve the Reliability of Intra-Operative Neuromonitoring Signals: Online Signal Processing of Internal Anal Sphincter Activity. Color. Dis. 2011, 13, 1422–1427. [Google Scholar] [CrossRef]
  25. Filips, A.; Haltmeier, T.; Kohler, A.; Candinas, D.; Brügger, L.; Studer, P. LARS Is Associated with Lower Anastomoses, but Not with the Transanal Approach in Patients Undergoing Rectal Cancer Resection. World J. Surg. 2021, 45, 873–879. [Google Scholar] [CrossRef]
  26. Yan, M.; Lin, Z.; Wu, Z.; Zheng, H.; Shi, M. A Predictive Nomogram Model for Low Anterior Resection Syndrome after Rectal Cancer Resection. ANZ J. Surg. 2022, 92, 3224–3231. [Google Scholar] [CrossRef] [PubMed]
  27. Brescia, A.; Muttillo, E.M.; Angelicone, I.; Madaffari, I.; Maggi, F.; Sperduti, I.; Gasparrini, M.; Osti, M.F. The Role of Indocyanine Green in Laparoscopic Low Anterior Resections for Rectal Cancer Previously Treated with Chemo-Radiotherapy: A Single-Center Retrospective Analysis. Anticancer Res. 2022, 42, 211–216. [Google Scholar] [CrossRef]
  28. Ahmad, N.Z.; Abbas, M.H.; Khan, S.U.; Parvaiz, A. A Meta-Analysis of the Role of Diverting Ileostomy after Rectal Cancer Surgery. Int. J. Color. Dis. 2021, 36, 445–455. [Google Scholar] [CrossRef]
  29. Niu, L.; Wang, J.; Zhang, P.; Zhao, X. Protective Ileostomy Does Not Prevent Anastomotic Leakage after Anterior Resection of Rectal Cancer. J. Int. Med. Res. 2020, 48, 030006052094652. [Google Scholar] [CrossRef]
  30. Mu, Y.; Zhao, L.; He, H.; Zhao, H.; Li, J. The Efficacy of Ileostomy after Laparoscopic Rectal Cancer Surgery: A Meta-Analysis. World J. Surg. Oncol. 2021, 19, 318. [Google Scholar] [CrossRef]
  31. Vogel, I.; Reeves, N.; Tanis, P.J.; Bemelman, W.A.; Torkington, J.; Hompes, R.; Cornish, J.A. Impact of a Defunctioning Ileostomy and Time to Stoma Closure on Bowel Function after Low Anterior Resection for Rectal Cancer: A Systematic Review and Meta-Analysis. Tech. Coloproctology 2021, 25, 751–760. [Google Scholar] [CrossRef] [PubMed]
  32. Parnasa, S.Y.; Chill, H.; Helou, B.; Cohen, A.; Alter, R.; Shveiky, D.; Mizrahi, M.I.; Abu-Gazala, A.; Pikarsky, J.; Shussman, N. Low anterior resection syndrome following rectal cancer surgery: Are incidence and severity lower with long-term follow-up? Tech. Coloproctology 2022, 26, 981–989. [Google Scholar] [CrossRef] [PubMed]
  33. He, S.; Zhang, J.; Wang, R.; Li, L.; Shi, L.; Ren, D.; Wang, J.; Deng, Y.; Dou, R. Impact of long-course neoadjuvant radiation on postoperative low anterior resection syndrome and stoma status in rectal cancer: Long-term functional follow-up of a randomized clinical trial. BJS Open 2022, 6, zrac127. [Google Scholar] [CrossRef] [PubMed]
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Figure 1. Flowchart.
Figure 1. Flowchart.
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Figure 2. LARS questionnaire by Emmertsen et al., Annals of Surgery, 2012 [9].
Figure 2. LARS questionnaire by Emmertsen et al., Annals of Surgery, 2012 [9].
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Figure 3. Time to stoma closure and incidence of LARS.
Figure 3. Time to stoma closure and incidence of LARS.
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Table 1. General features of study population.
Table 1. General features of study population.
ParameterCategoryValue (n = 78)
Median (IQR) or n (%)
Age, years 65 (57, 73)
SexFemale30 (38%)
Male48 (62%)
ASAI4 (5%)
II46 (59%)
III28 (36%)
IV0 (0%)
Distance from anal verge0–5 cm10 (13%)
5–10 cm30 (38%)
10–15 cm38 (49%)
TNM Stage05 (6.4%)
120 (26%)
2a14 (18%)
2b3 (3.8%)
3a6 (7.7%)
3b21 (27%)
3c6 (7.7%)
4a3 (3.8%)
ASA: American Society of Anesthesiologists score, IQR: interquartile range.
Table 2. Intraoperative and perioperative features.
Table 2. Intraoperative and perioperative features.
ParameterCategoryValue (n = 78)
Mean (IQR) or n (%)
Surgical techniqueOpen53 (68%)
VLS25 (32%)
Operative time, minMedian (IQR)210 (180, 248)
IleostomyYes29 (37%)
No49 (63%)
Stoma closure, weeksMedian (IQR)25 (13, 51)
nRTLCRT24 (31%)
SCRT4 (5%)
No50 (64%)
Adjuvant therapyCHT6 (8%)
RT1 (1%)
No69 (90%)
MorbidityYes11 (17%)
No58 (83%)
Clavien-Dindo Score13 (4%)
24 (6%)
3a1 (1%)
3b4 (6%)
LARS ScoreNo LARS54 (69%)
Minor LARS13 (17%)
Major LARS11 (14%)
nRT: neoadjuvant radiotherapy, LCRT: long course radiotherapy, SCRT: short course radiotherapy, LARS: low anterior resection syndrome, IQR: interquartile range.
Table 3. Factors associated with LARS. Bold format dates mean the statistically significant data.
Table 3. Factors associated with LARS. Bold format dates mean the statistically significant data.
ParameterTotal LARSMinor LARSMajor LARS
L0
(n = 54)		TL
(n = 24)		p ValueL0
(n = 54)		mL
(n = 13)		p ValueL0
(n = 54)		ML
(n = 11)		p Value
Age, yearsMedian (IQR)67(57, 75)65 (55, 68)0.15967 (57, 75)62 (53, 66)0.17267 (57, 75)65 (56, 69)0.446
Sex, n (%)Female18 (60%)12 (40%)0.16318 (72%)7 (28%)0.20918 (78%)5 (22%)0.500
Male36 (75%)12 (25%) 36 (86%)6 (14%) 36 (86%)6 (14%)
ASA, n (%)12 (50%)2 (50%)0.3152 (67%)1 (33%)0.2212 (67%)1 (33%)0.717
230 (65%)16 (35%) 30 (75%)10 (25%) 30 (83%)6 (17%)
322 (79%)6 (21%) 22 (92%)2 (8%) 22 (85%)4 (15%)
Distance from anal verge, n (%)0–5 cm6 (60%)4 (40%)0.1806 (67%)3 (33%)0.5156 (86%)1 (14%)0.041
5–10 cm18 (60%)12 (40%) 18 (82%)4 (18%) 18 (69%)8 (31%)
10–15 cm30 (79%)8 (21%) 30 (83%)6 (17%) 30 (94%)2 (6%)
Tumor dimension, cmMedian (IQR)3.15 (2.20, 4.50)2.50 (1.85, 3.00)0.0523.15 (2.20, 4.50)2.50 (2.00, 2.50)0.0133.15 (2.20, 4.50)2.50 (1.78, 4.88)0.752
pT, n (%)T02 (67%)1 (33%)0.1072 (100%)0 (0%)0.0072 (67%)1 (33%)0.323
Tis1 (50%)1 (50%)1 (50%)1 (50%)1 (100%)0 (0%)
T16 (67%)3 (33%)6 (86%)1 (14%)6 (75%)2 (25%)
T29 (50%)9 (50%)9 (53%)8 (47%)9 (90%)1 (10%)
T331 (84%)6 (16%)31 (94%)2 (6.1%)31 (89%)4 (11%)
T4a4 (57%)3 (43%)4 (100%)0 (0%)4 (57%)3 (43%)
T4b1 (50%)1 (50%)1 (50%)1 (50%) 1 (100%)0 (0%)
pN, n (%)N030 (68%)14 (32%)0.16830 (79%)30 (79%)0.10430 (83%)30 (83%)0.309
N119 (79%)5 (21%)8 (21%)8 (21%)6 (17%)6 (17%)
N25 (50%)5 (50%)19 (90%)19 (90%)19 (86%)19 (86%)
G, n (%)G02 (100%)0 (0%)0.1892 (100%)0 (0%)>0.9992 (100%)0 (0%)0.038
G13 (100%)0 (0%)3 (100%)0 (0%)3 (100%)0 (0%)
G232 (78%)9 (22%)32 (82%)7 (18%)32 (94%)2 (5.9%)
G38 (53%)7 (47%)8 (80%)2 (20%)8 (62%)5 (38%)
Surgical Technique, n (%)Open36 (68%)17 (32%)0.71636 (78%)10 (22%)0.74036 (84%)7 (16%)>0.999
VLS18 (72%)7 (28%)18 (86%)3 (14%)18 (82%)4 (18%)
Operative time, minMedian (IQR)210 (180, 255)208 (170, 229)0.249210 (180, 255)195 (155, 225)0.131210 (180, 255)210 (193, 235)0.854
IleostomyYes17 (59%)12 (41%)0.11817 (77%)5 (23%)0.74517 (71%)7 (29%)0.083
No37 (76%)12 (24%)37 (82%)8 (18%)37 (90%)4 (10%)
Time to stoma closure, weeksMedian (IQR)19 (12, 26)43 (14, 71)0.10619 (12, 26)46 (13, 51)0.41019 (12, 26)39 (22, 74)0.105
Neoadjuvant therapyLCRT16 (67%)8 (33%)0.64216 (80%)4 (20%)0.20116 (80%)4 (20%)0.815
SCRT2 (50%)2 (50%)2 (50%)2 (50%)2 (100%)0 (0%)
No36 (72%)14 (28%)36 (84%)7 (16%)36 (84%)7 (16%)
Adjuvant therapyCHT4 (67%)2 (33%)0.6084 (67%)2 (33%)0.6724 (100%)0 (0%)0.327
RT1 (100%)0 (0%)1 (100%)0 (0%)1 (100%)0 (0%)
CHT + RT0 (0%)1 (100%)000 (0%)1 (100%)
No48 (70%)21 (30%)48 (81%)11 (19%)48 (83%)10 (17%)
Table 4. Multivariate analysis of factors associated with LARS. Bold format dates mean the statistically significant data.
Table 4. Multivariate analysis of factors associated with LARS. Bold format dates mean the statistically significant data.
ParameterTotal LARSMinor LARSMajor LARS
OR95% CIp ValueOR95% CIp ValueOR95% CIp Value
Distance from anal verge0–5 cm--0.006--0.9--0.002
5–10 cm5.580.65, 77.90.990.02, 52.0>10000.00, >1000
10–15 cm0.190.01, 2.330.350.00, 23.40.460.00, >1000
Tumor dimension, cmMedian0.600.35, 0.940.0250.130.01, 0.44<0.0010.760.27, 1.900.5
pTT0--0.015--0.003--0.2
T10.910.03, 40.2>10000.00, NA0.210.00, 16.5
T29.050.36, 464>10000.00, NA0.520.00, 71.1
T30.910.04, 33.8>10000.00, NA0.360.01, 20.5
T4a18.80.31, >10000.000.00, >1000>10000.00, >1000
T4b>10000.00, NA>10000.00, NA>10000.00, >1000
Tis14.60.19, >1000>10000.00, NA0.570.00, >1000
pNN0--0.13--0.6--0.3
N1a0.820.08, 6.310.00 4.600.29, 102
N1b0.260.01, 2.888.020.02, >10000.000.00, >1000
N1c0.00-0.00-0.00-
N2a9.740.46, 39514.10.06, >10000.940.00, >1000
N2b0.00-0.00-0.00-
Neoadjuvant therapyNo--0.3--0.066--0.6
LCRT0.190.02, 1.490.030.00, 2.900.280.02, 4.31
SCRT0.270.01, 8.2513.40.01, >10000.510.00, >1000
Adjuvant TherapyNo--0.004--0.012--0.007
CHT0.570.03, 7.14>10004.21, >10000.000.00, >1000
RT0.00-0.00-0.050.00, >1000
CHT + RT>10000.00, NA-->10000.00, >1000
OR: odds ratio, CI: confidence interval, LCRT: long course radiotherapy, SCRT: short course radiotherapy.
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Muttillo, E.M.; La Franca, A.; Coppola, A.; Li Causi, F.S.; Checchelani, M.; Ceccacci, A.; Castagnola, G.; Garbarino, G.M.; Osti, M.F.; Balducci, G.; et al. Low Anterior Resection Syndrome (LARS) after Surgery for Rectal Cancer: An Inevitable Price to Pay for Survival, or a Preventable Complication? J. Clin. Med. 2023, 12, 5962. https://doi.org/10.3390/jcm12185962

AMA Style

Muttillo EM, La Franca A, Coppola A, Li Causi FS, Checchelani M, Ceccacci A, Castagnola G, Garbarino GM, Osti MF, Balducci G, et al. Low Anterior Resection Syndrome (LARS) after Surgery for Rectal Cancer: An Inevitable Price to Pay for Survival, or a Preventable Complication? Journal of Clinical Medicine. 2023; 12(18):5962. https://doi.org/10.3390/jcm12185962

Chicago/Turabian Style

Muttillo, Edoardo Maria, Alice La Franca, Alessandro Coppola, Francesco Saverio Li Causi, Marzia Checchelani, Alice Ceccacci, Giorgio Castagnola, Giovanni Maria Garbarino, Mattia Falchetto Osti, Genoveffa Balducci, and et al. 2023. "Low Anterior Resection Syndrome (LARS) after Surgery for Rectal Cancer: An Inevitable Price to Pay for Survival, or a Preventable Complication?" Journal of Clinical Medicine 12, no. 18: 5962. https://doi.org/10.3390/jcm12185962

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