As laparoscopy and even robotics become more widely used and the understanding of gastrointestinal anatomy refined, more and more patients with low rectal cancer can achieve tumor resection and anal preservation through various of sphincter-saving surgery. However, for ultra-low rectal cancers near the anus, which are located too close to the anus and have too little pelvic space, especially in men, APR is still the standard procedure to achieve a negative resection margin, but the postoperative permanent to the pain of patients underwent colostomy and inconvenience is indelible, some patients even give up treatment because they could not accept postoperative colostomy. Thus, it has always been the research direction of gastrointestinal surgery to ensure the radical resection of tumor while preserving the patient's anus and maintaining the original gastrointestinal structure. ISR was first proposed by Professor Lyttle and Professor Parks in 1977 for the treatment of patients with inflammatory bowel disease requiring colon and rectal resection, and it was first used in 1994 to treat rectal cancer less than 5 cm from the anal margin. ISR dissects part or all of the internal sphincter by dissecting the sphincter space, and sutures the proximal colon and anal canal. It emphasizes the correct separation of the inner and outer sphincter. The range of internal anal sphincter resection based on tumor location is divided into complete ISR (complete resection of internal sphincter, resection at the sphincter groove), subtotal ISR (subtotal resection of internal sphincter, resection between dentate line and sphincter groove) and partial ISR (partial removal of the internal sphincter, removal at the dentate line) . The proposal of ISR has brought hope to patients and the medical community, but also brought us a series of questions, such as the radical tumor problem and the anal function of patients after surgery.
This study compared a series of outcomes of ISR versus APR surgery for ultra-low rectal cancer patients in our center, including the short-term, oncological and functional outcomes. Our data showed that ISR may provide a feasible and safety alternative to APR based on the oncologic cure rate and defecation function.
In our study, ISR group showed shorter operative time and less blood loss than APR group. Moreover, the mean length of postoperative hospital stay was shorter in ISR group, although there were no statistical differences. In addition, 30-day complications and Clavien–Dindo score showed no statistical difference between the two groups, among them, anastomotic leakage was the main complication in the ISR group, while hemorrhage was the main complication in the APR group. Clinically, we consider that the main causes of anastomotic leakage including: (1) low anastomosis, difficult operation; (2) poor blood supply or excessive tension in the anastomosis; (3) more opportunities for pelvic and intestinal contamination. Because APR permanently closes the anus, the anastomotic leakage can be greatly reduced or avoided, and the postoperative complications mainly come from the large trauma caused by the surgery itself. Therefore, surgeons should fully understand the various complications, comprehensively evaluate patients before surgery, correctly grasp the surgical indications, make preventive stoma when appropriate, what’s more, surgical skills and experience are also very important. These short outcomes demonstrated that ISR may provide a safe alternative to APR, with less surgical trauma and faster recovery.
In recent years, the survival results of ISR and APR have been reported in several studies. Rullier et al. found that the combination of preoperative radiotherapy with sphincter-saving procedures not only may facilitate good perioperative and functional outcomes, but is also safe from the oncological point of view . Schiessel et al. studied 121 rectal cancer patients who underwent ISR. After 16 years of follow-up, they found that there were no statistically significant differences in postoperative survival and recurrence rate between patients with ISR compared with low anterior resection (LAR) and APR . Shunsuke Tsukamoto et al. followed up 285 patients (112 ISR and 173 APR) by propensity score matching and found the similar oncologic outcomes for ISR and APR without preoperative chemoradiotherapy in patients with low rectal cancer . In our study, the overall survival, disease-free survival and local recurrence rate were similar between the two groups, R0 resection achieved 100% in both the groups and the number of lymph nodes harvested showed no difference, indicating that oncological outcomes and surgical efficacy were similiar between ISR and APR. In addition, we found that postoperative local recurrence or metastasis in the ISR group mostly occurred in patients with poorly differentiated tumors, or with a small number of lymph node detection, suggesting that ISR surgery should be carefully selected for patients with poorly differentiated tumors with very low rectal cancer. For patients with insufficient lymph node detection, postoperative follow-up interval should be shortened and close observation should be conducted.
Although our study and another previous studies have confirmed the oncology safety of ISR, whether patients can obtain good stool control after surgery due to partial or complete loss of the internal sphincter is always a concern. Most scholars believe that preserving all internal sphincter and mucosa is the key to maintaining good stool control function after the surgery . When the distance between the lower edge of the tumor and the anorectal ring is less than 2 cm, most or even all internal sphincters need to be removed to ensure the radical treatment effect, and the patient will have severe defecation control dysfunction and even anal incontinence. To avoid this outcome, APR is often preferred. Due to the removal of part or all of the internal sphincter in ISR surgery, defecation control dysfunction will inevitably occur after a period of time, but the ability to control defecation can be recovered to varying degrees within 3 to 6 months after surgery. In our study, most of the patients after ISR presented with low anterior resection syndrome to varying degrees, but according to LARS score and Wexner score, the anal function of the vast majority of patients after ISR was satisfactory. Yamada et al.  also considered that postoperative anal function of ISR was generally satisfactory, and found no significant difference in postoperative defecation times between patients with partial internal sphincter resection and patients with subtotal resection, but anal function was relatively poor in patients with complete ISR. Therefore, it is of great significance to retain as much internal anal sphincter as possible to maintain good postoperative stool control. Motoi Koyama et al.  suggested that younger patients with T1 or T2 rectal cancers who require no preoperative therapy are ideal candidates for ISR. We believe that laparoscopy has significant implications for the safety and efficacy of oncology. With the help of the magnification effect of the laparoscope, the visual field can be exposed more clearly, the clearance and approach selection can be more accurate, and the perirectal tissue damage can be more effectively avoided. At the same time, the principle of total mesorectal excision should be strictly followed, and the peripheral incision edge should be kept smooth and intact, and the instinctual sense receptors located outside the intestinal wall should be preservated. This is of great significance for the recovery of postoperative anal function.
Currently, comprehensive treatment is emphasized for low and ultra-low rectal Cancer. According to the latest National Comprehensive Cancer Network (NCCN) guidelines, neoadjuvant radiotherapy and chemical therapy are recommended for t3-4 or patients with positive lymph node metastasis, which can reduce the tumor stage, reduce the positive rate of circumcircumential resection edge and improve the anal retention rate. However, many scholars believe that neoadjuvant chemoradiotherapy would increase the incidence of anastomotic fistula and impair postoperative anal function . Ito etc.  had performed postoperative anal function evaluation in 96 cases of patients with the ISR, single factor analysis showed that excessive internal sphincter resection range and preoperative radiotherapy and chemical drug treatment is the adverse factors that affect the anus function, multi-factor analysis showed that only the preoperative radiation therapy and chemical therapy is the independent factors affect the anus function, has nothing to do with internal sphincter resection range. In order to avoid the adverse effects of neoadjuvant therapy on postoperative anal function and anastomotic healing, all patients did not receive preoperative radiotherapy or chemotherapy in this study.
The limitations of this study are retrospective and nonrandomized design of a single center and selection bias of patient. In addition, the sample size is also limited and the skill and experience of the surgeon may influence the outcome. Therefore, it is necessary to expand the sample size and carry out multi-center research.