Does anastomotic leakage after intersphincteric resection for ultralow rectal cancer influence long-term outcomes? A retrospective observational study

doi:10.21203/rs.3.rs-2951271/v1

Purpose

To determine whether anastomotic leakage (AL) following intersphincteric resection (ISR) for ultralow rectal cancer (uLRC) is associated with long-term negative outcomes.

Methods

Between June 2011 and January 2022, 236 consecutive patients who underwent ISR with diverting ileostomy for uLRC were included. The primary outcome was long-term clinical consequences of AL, including chronic stricture, stoma reversal, oncological and functional results.

Results

Forty-one (17.4%) patients developed symptomatic AL, whereas only two (0.8%) required re-laparotomy due to severe leakage. Patients with leaks had a significantly increased incidence of chronic stricture (29.3% vs 8.7%, P = 0.001) and stoma non-reversal (34.1% vs 4.6%, P < 0.0001) than controls. The severe consequences were particularly common in patients with anastomotic separation, resulting in 60% of those presenting with chronic stricture and 50% ending up with stoma non-reversal. After a median follow-up of 59 (range, 7-139) months, AL did not compromise long-term oncological outcomes, including tumor recurrence (9.8% vs 5.6%, P = 0.3), 5-year disease-free and overall survival (73.4% vs 74.8% and 85.1% vs 85.4%, P = 0.56 and P = 0.55). A total of 149 patients with bowel continuity who completed self-assessment questionnaires were enrolled for functional evaluation. The median follow-up was 24 (range, 12–94) months after ileostomy reversal, and functional results were comparable between patients with and without leaks.

Conclusion

AL is an unfortunate reality for patients who underwent ISR for uLRC, but the rate of severe leakage is limited. Leaks contribute to possible adverse impacts on chronic stricture and stoma non-reversal, especially for patients with anastomotic separation. However, long-term oncological and functional results may not be compromised.

Intersphincteric resection

Anastomotic leakage

Long-term outcomes

Ultralow rectal cancer

Intersphincteric resection (ISR) could represent an excellent alternative to abdominoperineal resection to avoid permanent colostomy for selected patients with ultralow rectal cancer (uLRC) [1–3]. The ISR procedure requires partial or total excision of the internal anal sphincter to obtain adequate surgical margins and conducts a coloanal anastomosis (CAA) to restore intestinal continuity. The extreme distal anastomoses are located below the anorectal ring, where the neorectal and mesenteric compression into the anal canal is inevitable after surgery [4, 5]. Therefore, it is theoretically possible that patients undergoing ISR are more vulnerable to anastomotic healing deficiencies.

Previous studies have demonstrated that anastomotic leakage (AL) is the most frequent complication after ISR, with its incidence ranging from 0.9–48%, depending upon definition [6, 7]. This wide variation might be attributed to the application of a temporary diverting stoma, which is routinely recommended for ISR patients to alleviate the consequences of symptomatic AL [8–10]. In the immediate postoperative period, the diagnosis of AL is not always evident in that proximal fecal diversion may prevent leaks from manifesting prominent clinical signs. Similarly, the limited available publications reported different risk factors for AL following ISR [8, 11, 12]. Whether AL is associated with worse oncological outcomes among patients who underwent low anterior resection (LAR) for rectal cancer remains controversial [13–15]. To our knowledge, literature provides scarce data concerning this aspect for ISR patients, albeit with an increased risk of AL.

In addition to oncologic outcomes, AL following sphincter preservation surgery deserves special consideration due to a potential negative impact on chronic stricture, permanent stoma formation, bowel function, and even quality of life. However, few studies exist examining the clinical implications of leaks for ISR patients [16, 17]. The present study aimed to determine whether AL following ISR influences long-term outcomes in patients with uLRC. The hypothesis was that these surgical results would be adversely affected in ISR patients after AL.

Study design

A retrospective observational study was conducted that determined the patients who underwent ISR with diverting ileostomy for uLRC between June 2011 and January 2022. The study protocol was approved by our institutional ethics committee. Data were obtained from the prospectively maintained database.

Neoadjuvant therapy

Preoperative digital examination, pelvic MRI, and/or endorectal ultrasound were adopted for local staging of uLRC. Because of the simultaneous consideration of oncological and functional outcomes, the selective radiotherapy strategy for locally advanced cancer (T3-4 or N+) was implemented as we described previously [17]. Neoadjuvant chemoradiotherapy or total neoadjuvant therapy was routinely performed for patients with MRI-detected involvement of circumferential resection margin. Surgery was carried out 6–12 weeks after completion of long-course radiotherapy. Neoadjuvant chemotherapy without radiotherapy was recommended for high-risk patients with MRI-predicted extramural venous invasion or tumor deposits [18]. Those patients who refused neoadjuvant therapy proceeded straight to surgery only if an R0 resection could be achievable.

Surgical procedure

According to the surgical classification for uLRC [19], ISR was indicated for juxta-anal (lesions ≤ 1 cm from the anorectal ring) and intra-anal (lesions with internal sphincter invasion) tumors. Contraindications included transanal tumors (lesions with external sphincter or levator ani muscles invasion), poorly differentiated tumors, and poor anal function.

Mechanical bowel preparation the day before surgery and antibiotic prophylaxis with induction of surgery were administered. Details of the ISR procedure have been reported previously [4, 10]. Low inferior mesenteric artery ligation with D3 lymph node dissection was used for preservation and maximization of perfusion. Since March 2018, patients have received indocyanine green (ICG) fluorescence angiography to ensure blood supply of the proximal colon. Straight hand-sewn CAA or stapled anastomosis with reinforced sutures was performed in the condition of tension-free reconstruction. A diverting loop ileostomy in combination with pelvic drainage was constructed routinely. The ileostomy was planned for reversal at 3–6 postoperative months if patients without endoscopic or radiographic evidence of anastomotic morbidity.

Symptomatic AL

Aside from general clinical symptoms of AL, patients with suspiciously local signs were confirmed by digital examination, endoscopy, and CT scan. The definition of symptomatic AL was used the diagnostic criteria recommended by the International Study Group of Rectal Cancer (ISREC) [20]. Asymptomatic AL was not registered because contrast enema radiography was not routinely adopted. Early and delayed AL were defined as postoperative leaks diagnosed within or more than 30 days after surgery [21]. Additionally, anastomotic separation (AS) was defined as complete dehiscence of neorectal walls at the anastomotic site [16].

Follow-up and outcome definition

Patients were required to follow up one month after discharge for rapid recognition and management of late anastomotic complications. Chronic stricture was defined as a narrowing of the anastomosis that prevented passage through a 12-mm colonoscope [22]. Stoma non-reversal was defined as the continued presence of a diverting stoma after ISR, including non-closure of the primary ileostomy and reconstruction of a replacement colostomy.

Long-term oncological results were recorded in all patients. Patient follow-up was performed every three months for two years and then every six months for at least three years. Local recurrence was defined as evidence of tumor relapse in the pelvis (tumor bed, pelvic nodes, anastomosis, drain site, or perineum), occurring alone or with other sites [23].

Wexner incontinence score (WIS) and low anterior resection syndrome (LARS) score were used as specific patient-reported outcome measures to determine neorectal function for patients with at least 12 months of follow-up after reversal. The WIS ranges from 0 (normal continence) to 20 (severe incontinence); major incontinence was defined as a score ≥ 10, moderate incontinence 5–9, and good continence 0–4 [10]. The LARS score provides a categorization of patients into three groups: no LARS (0–20), minor LARS (21–29), and major LARS (30–42) [24]. The index of patients’ subjective perception of postoperative function was evaluated by visual analog scale (VAS) with scores from 0 (worst) to 10 (best).

Statistical analysis

In line with the data distributions, means (standard deviations) and medians (ranges) were reported for continuous data. Counts (percentages) were calculated for categorical data. Groups were analyzed by Mann-Whitney U test, Kruskal-Wallis test, chi-square test, or Fisher’s exact test where appropriate. The Kaplan-Meier method was used to calculate the cumulative incidence of stoma non-reversal, disease-free survival (DFS), and overall survival (OS), and the log-rank test was used for comparison. A P value < 0.05 was considered statistically significant.

Incidence and management of symptomatic AL

Table 1 outlines clinicopathological characteristics in the study group, specified as with or without AL. There were 41 patients developed symptomatic AL, including early leaks (n = 30) and delayed leaks (n = 11), yielding an overall AL rate of 17.4%. With the exception of BMI and diabetes mellitus, no differences between the three groups were found in terms of patients’ characteristics. Multivariate analysis revealed that obesity (OR = 3.16, P = 0.02) and diabetes mellitus (OR = 2.99, P = 0.02) were independently predictive of early AL, but the baseline characteristics were not associated with delayed AL (Supplement Table 1 and 2). Moreover, the AL rate did not differ significantly before and after the administration of ICG (18.7% vs 15.9%, P = 0.58).

Figure 1 depicts the clinical management of symptomatic AL. Two (0.8%) patients with early AL required re-laparotomy due to sepsis and neorectum necrosis. The median time of the initial diagnosis of early AL was 9 (range, 2-17) days after surgery, with 63.3% (19/30) of the leaks occurring over the first week of the operation. And the median interval time was 3 (range, 1-6) months after surgery for delayed AL. AS occurred in 10 (4.2%) patients with a median time of 11 (range, 3-17) days to clinical diagnosis; in addition, a trans-anal drainage tube was used to bridge the intestinal wall in 70% (7/10) of these patients.

Chronic stricture and stoma non-reversal

Chronic stricture occurred in 29 (12.3%) patients, of whom 12 (29.3%) with AL and 17 (8.7%) without AL (P = 0.001, Figure 2A). Additionally, the incidence was significantly increased in both the early AL group and the delayed AL group when compared with the control group (33.3% vs 18.2% vs 8.7%, P = 0.001). Among patients with AL, a significant higher rate of stricture was noted in the AS subgroup compared to the no-AS subgroup (60% vs 19.4%, P = 0.04, Figure 2B).

Stoma non-reversal was eventually documented in 23 (9.7%) patients, including 14 cases of the AL group (Figure 1) and 9 of the control group (34.1% vs 4.6%, P < 0.0001). The reasons for stoma non-reversal were anastomotic morbidity (n = 9), metastatic disease (n = 8), recurrent disease (n = 3), patients’ refusal (n = 1), poor general condition (n = 1), and peri-operative mortality (n = 1). At 12-months after the index operation, the cumulative incidence of stoma non-reversal was 2.9% in the control group, but 20.6% in the AL group (P < 0.0001). Besides, the median time to stoma closure was significantly longer in the AL group than that in the control group [4.6 (range, 3.1-11.1) months vs 3.7 (range, 2.7-19.9) months, P = 0.001]. The diverting stomas were not closed in 50% (5/10) of patients with AS; however, 71.4% (5/7) of those who treated with the trans-anal drainage tube underwent stoma reversal.

Oncological outcomes

After a median follow-up of 59 (range, 7-139) months, tumor recurrence occurred in 37 (15.7%) patients. Of these, 7 (3%) patients experienced local recurrence, 27 (11.4%) distant metastasis, and 8 (3.4%) both local and distant recurrence. The median time from surgery to local recurrence and distant metastasis was 12 (range, 5-53) months and 13 (range, 3-60) months, respectively.

The local recurrence rate was lower in patients without leaks than those with leaks, but the difference was not statistically significant (5.6% vs 9.8%, P = 0.3). Furthermore, no differences were found in terms of local recurrence and distant metastasis between the early AL, delayed AL, and control groups (Table 1). The 5-year OS and DFS in this series were 85.3% and 74.5%, respectively. As shown in Figure 3, there were also no differences between the AL and control groups in the 5-year DFS (73.4% vs 74.8%) and OS (85.1% vs 85.4%).

Functional outcomes

A total of 173 patients with bowel continuity were enrolled for functional assessment, of these 149 (86.1%) returned their self-assessment questionnaires (Figure 4). There were no significant differences in clinicopathological characteristics between responders and non-responders (Table 2). The response rate among the AL and control group was 87% and 86% (P = 1.0), respectively. When evaluating the 149 patients with bowel continuity, the incidence of chronic stricture was higher in the AL group than that in the control group (25% vs 8.5%, P = 0.04).

The median follow-up of patients involved in the functional evaluation was 24 (range, 12-94) months, with no difference between the AL and control groups (P = 0.9, Table 3). Functional scoring systems (including the WIS, LARS score, and VAS score) were comparable between the groups. Moreover, no differences in the proportion of both major incontinence and major LARS were found between patients with and patients without AL.

This study described the clinical impact of AL on patients undergoing ISR with diverting ileostomy for uLRC. Consistent with our previously published data [17], we found that nearly 1 in 8 patients occurred early AL after ISR. The higher AL rate in this study might be attributed to detailed documentation during the early postoperative period. Even though the diverting ileostomy prevents leaks from manifesting prominent clinical symptoms, we paid more attention to the local leakage signs, including mucosa ischemia, exfoliation, necrosis, turbid discharge, and fecal content from the pelvic drainage. Moreover, digital examination findings are valuable and confirmatory for AL because the distal anastomoses are situated near the anal verge. Our reported rate was concordant with the 25-year experience on ISR from Bordeaux [10], which indicated that the incidence of AL was 12.2%, with no difference between the three time periods. In the meanwhile, the AL rate did not obviously reduce over time in this series. Thus, an effective method of preventing or decreasing AL after ISR needs to be further elucidated.

Although the majority of early leaks were successfully managed with active therapeutic intervention, AS was an unexpected or unintended severe complication after ISR. We found that the incidence of AS was 4.2%, similar to the 3.8% reported rate by Yokota et al [16]. In our experience, AS commonly presents with mucosa ischemia and exfoliation in the early postoperative period and then results from subsequent leakage and anastomotic dehiscence. This process is supported by the median time of 11 days to clinical diagnosis of AS after surgery in this series. The occurrence of AS is also even rarer after colon surgery, but it could be resolved by endoscopic operation with self-expanding metal stents to bridge the intestinal wall [25]. For the distal separated anastomosis after ISR, there is no option to perform the technique; and, hence, a trans-anal drainage tube whereby connecting bowel tissue and mitigating subsequent stricture was used in 70% of our patients with AS.

AL predisposing the anastomosis to a chronic setting of inflammation is one of the most important causes of stricture formation [26]. We found a significantly increased incidence of chronic stricture in both patients with early and late leaks, which subsequently give rise to a delay of ileostomy reversal and a high risk of stoma non-reversal. The results were consistent with previous findings that AL was independently predictive of permanent stoma after ISR [17, 27]. Most notably, the adverse consequences were particularly common in patients with AS, resulting in 60% of those presenting with chronic stricture and 50% ending up with stoma non-reversal in this study. Nonetheless, 71.4% (5/7) of the AS patients who treated with trans-anal drainage tube underwent stoma reversal in this study. Since promising results previously reported that AS had a stricture incidence of 38.5% with a 3-year stoma reversal rate of 61.5% [16], we postulate that it would be possible to alleviate the negative consequences by early diagnosis and proactive management of AS after ISR.

Our data revealed that obesity and diabetes mellitus were independently predictive of early AL. This association could be explained by the fact that obesity, representing the surgical difficulty of ISR per se, makes surgical dissection in the deeper pelvis more technically challenging and more prone to anastomotic morbidity. Additionally, higher BMI and diabetes mellitus are associated with impaired microcirculation, adversely impacting the healing capacity of distal anastomoses [28, 29]. Although the two patient-related risk factors have been demonstrated among patients who underwent colorectal surgery [30], our data reaffirmed this association in the cohort of ISR patients. This result is an important addition to the literature, thus potentially contributing to better preoperative counseling and planning for high-risk patients.

There is a paucity of data concerning the late leaks after ISR. However, delayed AL cannot be considered a rare complication because its incidence following colorectal anastomosis has been reported to be 0.3%-4.3% [21]. The current study showed that 4.7% of ISR patients occurred late leaks, accounting for one-fourth of all AL. Of note, late leakage may develop through different mechanisms than early leakage after rectal surgery [31]. Previous study suggests that most risk factors for early leakage are surgery-related factors, whereas most risk factors for late leakage are patient-related factors [28]. We did not find the patient-related or surgery-related risk factors for delayed AL, probably because of the low number of these patients in this study.

For patients with rectal cancer, controversy exists as to whether or not AL has adverse effects on oncologic outcomes [13–15]. This discrepancy might be related to apparent differences in patient heterogeneity and study design types. More recently, an extended follow-up of a multicenter randomized controlled trial demonstrated that AL after LAR does not affect long-term OS, DFS, and tumor recurrence in patients with mid-low rectal cancer [14]. To our knowledge, there is no study to date determining this association for ISR patients, albeit with generally higher AL rates. This study is limited to ISR, and our data on oncological outcome fall within the range of previously published series [1–3, 5, 6]. Intriguingly, we found that AL following ISR did not compromise long-term oncological results (including local recurrence, distant metastasis, 5-year DFS and OS), which needs to be further confirmed in future research with a larger sample size.

Mounting evidence supports that functional concern instead of oncological outcomes has been the main limitation of ISR [5, 10]. As a consequence, AL following ISR deserves more special consideration because of the potential for functional impairment. In concordance with Clavien–Dindo classification system, Yokota et al [16] revealed that patients with major AL had similar WIS to those without AL at the 2-year follow-up after ISR. According to the ISREC criteria, our data showed that functional outcomes were comparable for ISR patients with or without leaks at a median follow-up of 24-months. These findings were consistent with the previous study with a median of 51 months follow-up, indicating that AL was not proven to be an independent predictor of poor continence after ISR [32]. Nevertheless, it should be noted that the diverting stomas were not closed in 34.1% of our patients with AL, of whom 35.7% (5/14) presented with subsequent major stricture. The results of this study, hence, would only be appropriate for leakage patients with bowel continuity. On the other hand, our subgroup analysis showed that chronic stricture could contribute to worse continence [WIS: 13 (range, 0–20) vs 8 (range, 0–20), P = 0.01]. In spite of a higher proportion of chronic stricture in the AL group, we did not find significant differences in functional outcomes between the groups, which might be ascribed to the improved impact of stricture on anal function after reversal of ileostomy, especially for those with successful intervention. Therefore, how to minimize AL and its sequelae is an imperative issue that may be essential to improving functional outcomes after ISR.

There were limitations in our study. First, this study was limited by its retrospective nature and limited sample size. Although data were prospectively collected, there is a potential for selection bias. Second, propensity score-matching was not employed for covariate balance because of the small number of leakage patients with stoma reversal. Third, previous literature showed that the WIS was poor in patients with major AL during the early period after ISR [16], but we did not determine the longitudinal course of functional outcomes and quality of life in this study. Lastly, only 14.8% of patients received preoperative radiotherapy, which is a predisposing factor for anastomotic morbidity and functional impairment [5, 27, 33].

In conclusion, although AL is an unfortunate reality for uLRC patients who underwent ISR with diverting ileostomy, the severe leakage rate is limited. Leaks contribute to possible adverse impacts on chronic stricture and ileostomy reversal, especially for patients with AS. However, the long-term oncological and functional results may not be compromised. It might be preferable to ameliorate the negative consequences through early detection and appropriate management of leaks for high-risk patients.

Authors’ contributions Study concept and design: Jianhua Ding, Bin Zhang, and Jianbin Xiang. Acquisition of data: Feifan Liu, Bin Zhang, Guangzuan Zhuo, and Yujuan Zhao. Analysis and interpretation of data: Bin Zhang, Feifan Liu, Yiming Zhou, and Jianbin Xiang. Drafting of manuscript: Bin Zhang and Jianhua Ding. Critical revision of manuscript: Bin Zhang, Jianbin Xiang, and Jianhua Ding. All the authors read and approved the final manuscript.

Clinical trial Chictr.org.cn identifier: ChiCTR-ONC-15007506 and ChiCTR2100051614.

Funding This study was supported by the National Natural Science Foundation of China (No. 82172845) and the Clinical Research Fund of Beijing Municipal Science and Technology Commission (No. Z211100002921044).

Competing interests The authors declare no competing interests.

Tsukamoto S, Miyake M, Shida D, Ochiai H, Yamada K, Kanemitsu Y (2018) Intersphincteric Resection Has Similar Long-term Oncologic Outcomes Compared With Abdominoperineal Resection for Low Rectal Cancer Without Preoperative Therapy: Results of Propensity Score Analyses. Dis Colon Rectum 61(9):1035–1042. https://doi.org/10.1097/DCR.0000000000001155
Rouanet P, Rivoire M, Gourgou S, Lelong B, Rullier E, Jafari M, Mineur L, Pocard M, Faucheron JL, Dravet F, Pezet D, Fabre JM, Bresler L, Balosso J, Lemanski C (2021) Sphincter-saving surgery after neoadjuvant therapy for ultra-low rectal cancer where abdominoperineal resection was indicated: 10-year results of the GRECCAR 1 trial. Br J Surg 108(1):10–13. https://doi.org/10.1093/bjs/znaa010
Liu ZH, Zeng ZW, Jie HQ, Huang L, Luo SL, Liang WF, Zhang XW, Kang L (2022) Transanal total mesorectal excision combined with intersphincteric resection has similar long-term oncological outcomes to laparoscopic abdominoperineal resection in low rectal cancer: a propensity score-matched cohort study. Gastroenterol Rep (Oxf) 10: goac026. https://doi.org/10.1093/gastro/goac026
Scala D, Niglio A, Pace U, Ruffolo F, Rega D, Delrio P (2016) Laparoscopic intersphincteric resection: indications and results. Updates Surg 68(1):85–91. https://doi.org/10.1007/s13304-016-0351-6
Collard M, Lefevre JH (2020) Ultimate Functional Preservation With Intersphincteric Resection for Rectal Cancer. Front Oncol 10: 297. https://doi.org/10.3389/fonc.2020.00297
Martin ST, Heneghan HM, Winter DC (2012) Systematic review of outcomes after intersphincteric resection for low rectal cancer. Br J Surg 99(5):603–12. https://doi.org/10.1002/bjs.8677
Shirouzu K, Murakami N, Akagi Y (2017) Intersphincteric resection for very low rectal cancer: A review of the updated literature. Ann Gastroenterol Surg 1(1):24–32. https://doi.org/10.1002/ags3.12003
Park IJ, Kim JC (2018) Intersphincteric Resection for Patients With Low-Lying Rectal Cancer: Oncological and Functional Outcomes. Ann Coloproctol 34(4):167–174. https://doi.org/10.3393/ac.2018.08.02
Rink AD, Kienle P, Aigner F, Ulrich A (2020) How to reduce anastomotic leakage in colorectal surgery-report from German expert meeting. Langenbecks Arch Surg 405(2):223–232. https://doi:10.1007/s00423-020-01864-5
Denost Q, Moreau JB, Vendrely V, Celerier B, Rullier A, Assenat V, Rullier E (2020) Intersphincteric resection for low rectal cancer: the risk is functional rather than oncological. A 25-year experience from Bordeaux. Colorectal Dis 22(11):1603–1613. https://doi.org/10.1111/codi.15258
Akasu T, Takawa M, Yamamoto S, Yamaguchi T, Fujita S, Moriya Y (2010) Risk factors for anastomotic leakage following intersphincteric resection for very low rectal adenocarcinoma. J Gastrointest Surg 14(1):104–11. https://doi.org/10.1007/s11605-009-1067-4
Toyoshima A, Nishizawa T, Sunami E, Akai R, Amano T, Yamashita A, Sasaki S, Endo T, Moriya Y, Toyoshima O (2020) Narrow pelvic inlet plane area and obesity as risk factors for anastomotic leakage after intersphincteric resection. World J Gastrointest Surg 12(10):425–434. https://doi.org/10.4240/wjgs.v12.i10.425
Zimmermann MS, Wellner U, Laubert T, Ellebrecht DB, Bruch HP, Keck T, Schlöricke E, Benecke CR (2019) Influence of Anastomotic Leak After Elective Colorectal Cancer Resection on Survival and Local Recurrence: A Propensity Score Analysis. Dis Colon Rectum 62(3):286–293. https://doi.org/10.1097/DCR.0000000000001287
Bao QR, Pellino G, Spolverato G, Restivo A, Deidda S, Capelli G, Ruffolo C, Bianco F, Cuicchi D, Jovine E, Lombardi R, Belluco C, Amato A, La Torre F, Asteria C, Infantino A, Contardo T, Del Bianco P, Delrio P, Pucciarelli S (2022) The impact of anastomotic leak on long-term oncological outcomes after low anterior resection for mid-low rectal cancer: extended follow-up of a randomised controlled trial. Int J Colorectal Dis 37(7):1689–1698. https://doi.org/10.1007/s00384-022-04204-9
Tschann P, Weigl MP, Szeverinski P, Lechner D, Brock T, Rauch S, Rossner J, Eiter H, Girotti PNC, Jäger T, Presl J, Emmanuel K, De Vries A, Königsrainer I, Clemens P (2022) Are risk factors for anastomotic leakage influencing long-term oncological outcomes after low anterior resection of locally advanced rectal cancer with neoadjuvant therapy? A single-centre cohort study. Langenbecks Arch Surg 407(7):2945–2957. https://doi.org/10.1007/s00423-022-02609-2
Yokota M, Ito M, Nishizawa Y, Kobayashi A, Saito N (2017) The Impact of Anastomotic Leakage on Anal Function Following Intersphincteric Resection. World J Surg 41(8):2168–2177. https://doi.org/10.1007/s00268-017-3960-4
Zhang B, Zhuo GZ, Zhao K, Zhao Y, Gao DW, Zhu J, Ding JH (2022) Cumulative Incidence and Risk Factors of Permanent Stoma After Intersphincteric Resection for Ultralow Rectal Cancer. Dis Colon Rectum 65(1):66–75. https://doi.org/doi: 10.1097/DCR.0000000000002036
Bhudia J, Glynne-Jones R, Smith T, Hall M (2020) Neoadjuvant Chemotherapy without Radiation in Colorectal Cancer. Clin Colon Rectal Surg 33(5):287–297. https://doi.org/10.1055/s-0040-1713746
Rullier E, Denost Q, Vendrely V, Rullier A, Laurent C (2013) Low rectal cancer: classification and standardization of surgery. Dis Colon Rectum 56(5):560–7. https://doi.org/10.1097/DCR.0b013e31827c4a8c
Rullier E, Denost Q, Vendrely V, Rullier A, Laurent C (2013) Low rectal cancer: classification and standardization of surgery. Dis Colon Rectum 56(5):560–7. https://doi.org/10.1097/DCR.0b013e31827c4a8c
Iwamoto M, Kawada K, Hida K, Hasegawa S, Sakai Y (2017) Delayed anastomotic leakage following laparoscopic intersphincteric resection for lower rectal cancer: report of four cases and literature review. World J Surg Oncol 15(1):143. https://doi.org/10.1186/s12957-017-1208-2
Qin Q, Ma T, Deng Y, Zheng J, Zhou Z, Wang H, Wang L, Wang J (2016) Impact of Preoperative Radiotherapy on Anastomotic Leakage and Stenosis After Rectal Cancer Resection: Post Hoc Analysis of a Randomized Controlled Trial. Dis Colon Rectum 59(10):934–42. https://doi.org/10.1097/DCR.0000000000000665
Marsh PJ, James RD, Schofield PF (1995) Definition of local recurrence after surgery for rectal carcinoma. Br J Surg 82(4):465–8. https://doi.org/10.1002/bjs.1800820412
Emmertsen KJ, Laurberg S; Rectal Cancer Function Study Group (2013) Impact of bowel dysfunction on quality of life after sphincter-preserving resection for rectal cancer. Br J Surg 100(10):1377–87. https://doi.org/10.1002/bjs.9223
Gu J, Deng S, Cao Y, Mao F, Li H, Li H, Wang J, Wu K, Cai K (2021) Application of endoscopic technique in completely occluded anastomosis with anastomotic separation after radical resection of colon cancer: a case report and literature review. BMC Surg 21(1):201. https://doi.org/10.1186/s12893-021-01202-6
Polese L, Vecchiato M, Frigo AC, Sarzo G, Cadrobbi R, Rizzato R, Bressan A, Merigliano S (2012) Risk factors for colorectal anastomotic stenoses and their impact on quality of life: what are the lessons to learn? Colorectal Dis 14(3):e124-8. https://doi.org/10.1111/j.1463-1318.2011.02819.x
Song O, Kim KH, Lee SY, Kim CH, Kim YJ, Kim HR (2018) Risk factors of stoma re-creation after closure of diverting ileostomy in patients with rectal cancer who underwent low anterior resection or intersphincteric resection with loop ileostomy. Ann Surg Treat Res 94(4):203–208. https://doi:10.4174/astr.2018.94.4.203
Sparreboom CL, van Groningen JT, Lingsma HF, Wouters MWJM, Menon AG, Kleinrensink GJ, Jeekel J, Lange JF; Dutch ColoRectal Audit group (2018) Different Risk Factors for Early and Late Colorectal Anastomotic Leakage in a Nationwide Audit. Dis Colon Rectum 61(11):1258–1266. https://doi.org/10.1097/DCR.0000000000001202
García-Granero E, Navarro F, Cerdán Santacruz C, Frasson M, García-Granero A, Marinello F, Flor-Lorente B, Espí A (2017) Individual surgeon is an independent risk factor for leak after double-stapled colorectal anastomosis: An institutional analysis of 800 patients. Surgery 162(5):1006–1016. https://doi:10.1016/j.surg.2017.05.023
Zarnescu EC, Zarnescu NO, Costea R (2021) Updates of Risk Factors for Anastomotic Leakage after Colorectal Surgery. Diagnostics (Basel) 11(12):2382. https://doi.org/10.3390/diagnostics11122382
Stewart DB (2021) Transanal Drainage Tubes-Prevention of Leaks or Unnecessary Sump? JAMA Surg 156(12):1158–1159. https://doi.org/10.1001/jamasurg.2021.4569
Denost Q, Laurent C, Capdepont M, Zerbib F, Rullier E (2011) Risk factors for fecal incontinence after intersphincteric resection for rectal cancer. Dis Colon Rectum 54(8):963–8. https://doi:10.1097/DCR.0b013e31821d3677
Lord AC, Corr A, Chandramohan A, Hodges N, Pring E, Airo-Farulla C, Moran B, Jenkins JT, Di Fabio F, Brown G (2022) Assessment of the 2020 NICE criteria for preoperative radiotherapy in patients with rectal cancer treated by surgery alone in comparison with proven MRI prognostic factors: a retrospective cohort study. Lancet Oncol 23(6):793–801. https://doi:10.1016/S1470-2045(22)00214-5

Table 1 Clinicopathological characteristics of patients undergoing ISR for ultralow rectal cancer

Patient characteristic

Overall

n = 236

Control

n = 195

Early AL

n = 30

Delayed AL

n = 11

P

Age at operation (years)

Gender, male/female

BMI (kg/m²)

ASA score, I/II/III-Ⅳ

Diabetes mellitus

Baseline serum CEA level (ng/ml)

Baseline serum CA-199 level (U/ml)

Baseline blood hemoglobin level (g/L)

Baseline serum albumin level (g/L)

Tumor height from anal verge (cm)

Neoadjuvant radiotherapy

Neoadjuvant chemotherapy

Surgical approach

Laparoscopic/open surgery

Partial/subtotal/total ISR

IMA, high ligation/low ligation

Straight anastomosis/transverse coloplasty

CAA, handsewn/stapled with reinforced sutures

Operative time (min)

Estimated blood loss (ml)

Distal resection margin (cm)

Maximal tumor size (cm)

Lymph nodes harvested

CRM involvement (≤1mm)

Distal margin involvement

Tumor stage (AJCC), 0-I/II/III/IV

Adjuvant chemotherapy

Tumor recurrence

Local recurrence

Distant metastasis

61 (25-84)

149/87 (63.1/36.9)

25 (18-36)

111/86/39 (47/36.4/16.5)

43 (19)

2.92 (0.24-110.8)

10.49 (0.6-479.4)

135 (51-173)

42.2 (32.2-50.6)

3 (1-5)

35 (14.8)

8 (3.4)

233/3 (98.7/1.3)

136/63/37 (57.6/26.7/15.7)

24/212 (10.2/89.8)

226/10 (95.8/4.2)

215/21 (91.1/8.9)

200 (120-400)

50 (10-400)

1.5 (0.5-4)

3.8 (0.7-9.5)

14 (1-31)

4 (1.7)

2 (0.8)

110/44/70/12 (46.6/18.6/29.7/5.1)

137 (58.1)

15 (6.4)

35 (14.8)

61 (25-84)

122/73 (62.6/37.4)

25 (18-34)

94/68/33 (48.2/34.9/16.9)

31 (15.9)

2.89 (0.24-110.8)

6.05 (0.6-479.4)

135 (86-173)

42.1 (33.2-50.6)

3 (1-5)

29 (14.9)

8 (4.1)

192/3 (98.5/1.5)

113/52/30 (57.9/26.7/15.4)

20/175 (10.3/89.7)

185/10 (94.9/5.1)

178/17 (91.3/8.7)

200 (120-400)

50 (10-400)

1.5 (0.5-4)

4 (0.7-9.5)

14 (2-31)

4 (2.1)

1 (0.5)

91/37/57/10 (46.7/19/29.2/5.1)

113 (57.9)

11 (5.6)

29 (14.9)

62 (47-71)

19/11 (63.3/36.7)

27 (20-36)

9/16/5 30/53.3/16.7)

12 (40)

3.03 (0.54-21.91)

8.5 (0.6-47.3)

140.5 (51-164)

43.2 (32.2-49.5)

4 (1-5)

3 (10)

0 (0)

30/0 (100/0)

17/8/5 (56.7/26.7/16.7)

3/27 (10/90)

30/0 (100/0)

27/3 (90/10)

215 (135-360)

50 (20-300)

1.5 (0.8-2.5)

3.5 (0.8-8.5)

13 (3-27)

0 (0)

1 (3.3)

12/6/10/2 (40/20/33.3/6.7)

15 (50)

3 (10)

61 (36-81)

8/3 (72.7/27.3)

26 (20-33)

8/2/1 (72.73/18.2/9.1)

0 (0)

3.45 (0.72-72.22)

15.4 (0.6-278.6)

136 (116-152)

40.4 (36.3-47.3)

3 (3-4)

3 (27.3)

0 (0)

11/0 (100/0)

6/3/2 (54.5/27.3/18.2)

1/10 (9.1/90.9)

11/0 (100/0)

10/1 (90.9/9.1))

225 (150-345)

50 (20-300)

1.5 (1-3)

3 (1.2-5)

14 (1-20)

0 (0)

7/1/3/0 (63.6/9.1/27.3/0)

9 (81.8)

1 (9.1)

3 (27.3)

0.77

0.89

0.008

0.13

0.003

0.97

0.84

0.45

0.59

0.73

0.35

0.73

1.0

0.99

1.0

0.61

0.9

0.11

0.46

0.37

0.63

1.0

0.32

0.93

0.19

0.41

0.35

Values are given as median (range) or n (%).

Abbreviations: ISR, intersphincteric resection; AL, anastomotic leakage; BMI, body mass index; ASA, American Society of Anesthesiologists; IMA, inferior mesenteric artery; CAA, coloanal anastomosis; CRM, circumferential resection margin; AJCC, American Joint Committee on Cancer (8th edition).

Table 2 Clinicopathological characteristics of responders and non-responders

Patient characteristic

Responders

n = 140

Non-responders

n = 24

P

Age at operation (years)

Gender, male/female

BMI (kg/m²)

ASA score, I/II/III-Ⅳ

Diabetes mellitus

Baseline serum CEA level (ng/ml)

Baseline serum CA-199 level (U/ml)

Baseline blood hemoglobin level (g/L)

Baseline serum albumin level (g/L)

Tumor height from anal verge (cm)

Neoadjuvant chemoradiotherapy

Surgical approach

Laparoscopic/open surgery

Partial/subtotal/total ISR

IMA, high ligation/low ligation

Straight anastomosis/transverse coloplasty

Handsewn/stapled CAA

Operative time (min)

Estimated blood loss (ml)

Distal resection margin (cm)

Maximal tumor size (cm)

Lymph nodes harvested

Tumor stage (AJCC), 0-I/II/III/IV

Adjuvant chemotherapy

57 ± 10

83/57 (59.3/40.7)

25.5 ± 3.43

68/51/21 (48.6/36.4/15)

28 (20)

2.7 (0.24-110.8)

9.5 (0.6-278.6)

134.6 ± 17.65

42.48 ± 3.62

3.5 (1.5-5.0)

18 (12.9)

139/1 (99.3/0.7)

84/40/16 (60/28.6/11.4)

14/126 (10/90)

138/2 (98.6/1.4)

129/11 (92.1/7.9)

195 (120-400)

50 (10-400)

1.5 (0.5-3.0)

3.8 (1.0-9.0)

14 (3-31)

64/28/45/3 (45.7/20/32.1/2.1)

83 (59.3)

57 ± 10

17/7 (70.8/29.2)

25.55 ± 3.8

17/5/2 (70.8/20.8/8.3)

0 (0)

3.07 (0.66-72.22)

11.45 (0.6-479.4)

133.1 ± 17.51

42.95 ± 3.64

3.0 (1.5-5.0)

3 (12.5)

24/0 (100/0)

13/4/7 (54.2/16.7/29.2)

1/23 (4.2/95.8)

24/0 (100/0)

22/2 (91.7/8.3)

210 (120-345)

50 (20-300)

1.5 (1.0-3.0)

3.8 (1.2-6.0)

12 (3-19)

12/4/8/0 (50/16.7/33.3/0)

10 (41.7)

0.69

0.28

0.95

0.16

0.02

0.22

0.74

0.71

0.56

0.58

1.0

0.08

0.7

1.0

0.12

0.8

0.62

0.82

0.06

0.97

0.11

Values are given as mean ± SD, median (range), or n (%) .

Abbreviations: BMI, body mass index; ASA, American Society of Anesthesiologists; ISR, intersphincteric resection; IMA, inferior mesenteric artery; CAA, coloanal anastomosis; AJCC, American Joint Committee on Cancer (8th edition).

Table 3 Functional results after ISR for ultralow rectal cancer

Characteristic

Overall

n = 149

AL

n = 20

Control

n = 129

P

(AL vs Control)

WIS [median (range)]

Subscales of WIS [mean (SD)]

Solid

Liquid

Gas

Wear pad

Life style alteration

Grade of WIS [n (%)]

0-4

5-9

10-20

LARS score [median (range)]

Grade of LARS score [n (%)]

No LARS (0-20)

Minor LARS (21-29)

Major LARS (30-42)

VAS [median (range)]

Months between reversal and survey [median (range)]

8 (0-20)

1.36 (1.41)

1.86 (1.28)

1.87 (1.44)

2.01 (1.71)

1.55 (1.44)

45 (31)

43 (27.9)

61 (41.1)

32 (0-42)

29 (19.5)

31 (20.8)

89 (59.7)

6 (0-10)

24 (12-94)

8.5 (0-20)

1.5 (1.54)

2.01 (1.32)

1.95 (1.54)

2.2 (1.58)

1.8 (1.24)

5 (25)

7 (35)

8 (40)

28.5 (11-41)

3 (15)

8 (40)

9 (45)

6 (2-10)

24 (12-75)

8 (0-20)

1.34 (1.39)

1.83 (1.28)

1.85 (1.43)

1.98 (1.74)

1.51 (1.46)

40 (31)

36 (27.9)

53 (41.1)

32 (0-42)

26 (20.2)

23 (17.8)

80 (62)

6 (0-10)

24 (12-94)

0.5

0.67

0.5

0.8

0.54

0.31

0.77

0.71

0.09

0.64

0.9

Abbreviations: ISR, intersphincteric resection; AL, anastomotic leakage; WIS, Wexner incontinence score; LARS, low anterior resection syndrome; VAS, visual analogue scale.

No competing interests reported.

Does anastomotic leakage after intersphincteric resection for ultralow rectal cancer influence long-term outcomes? A retrospective observational study

Status:

Journal Publication

Version 1

Abstract

Purpose

Methods

Results

Conclusion

Figures

Introduction

Methods

Study design

Neoadjuvant therapy

Surgical procedure

Symptomatic AL

Follow-up and outcome definition

Statistical analysis

Results

Discussion

Declarations

References

Tables

Additional Declarations

Supplementary Files

Status:

Journal Publication

Version 1