While the standard treatment modality for low-grade rectal cancer is transabdominal perineal resection (APR), several new techniques have emerged in recent years to treat low-grade rectal cancer. In an article published in World J Gastrointest Oncol, Dimitriou, MD, Greece, summarizes the indications, technical approach, and oncologic and functional outcomes of the new treatment techniques, emphasizing that treatment according to guidelines and patient characteristics will ensure maximum patient benefit.
Low-grade rectal cancer is defined as a tumor < 5 cm from the anal verge. The most fundamental advancement in rectal cancer surgery in the last 20 years or so has been the total mesorectal excision (TME) proposed by Dr. Heald in 1982, and although TME has never been compared prospectively with conventional surgical approaches, TME has clearly shown advantages in terms of control of local recurrence and survival compared to historical controls.
The standardized TME has a recurrence rate of < 10% and 5-year survival of 80%. The Dutch TME trial confirmed these results and clearly demonstrated an increased risk of local recurrence if patients underwent incomplete rectal mesenteric resection.
Laparoscopy provides better visualization of the pelvis and facilitates rectal resection. Although laparoscopic TME is a standardized and reproducible procedure, it is still technically complex. the rate of positive circumferential margins (CRM) after laparoscopic anterior resection in the UK MRC CLASICC trial was very high, and the location of the tumor in the mid-distal rectum was an important risk for a positive CRM. Patients with positive CRM (<1 mm) have an increased risk of local recurrence and distant metastasis and reduced overall survival, and TME techniques may reduce the rate of positive CRM.
Another change in the surgical treatment of rectal cancer is the re-evaluation of the distal resection margin (DRM) length, usually to ensure a 2 cm length. Because intra-distal bowel wall propagation or retrograde lymph node invasion is rare, and because recent review studies have shown no negative impact on local recurrence or overall survival in low-risk tumors when the DRM is <1 cm or even <5 mm, the TME technique allows for a shorter DRM and the circumferential anastomosis significantly reduces the transabdominal perineal resection rate.
A meta-analysis showed that patients treated with APR had a positive CRMs rate of 10%, a local recurrence rate of 20%, and a 5-year survival rate of 59%, whereas patients treated with LAR (low anterior rectal resection) had a positive CRMs rate of 5%, a local recurrence rate of 11%, and a 5-year survival rate of 70%, and the oncologic outcome after APR was not superior to that of LAR, and the worse outcome with APR may be due to defects in the surgical technique itself The worse outcome of APR may be caused by the defect of the surgical technique itself or the characteristics of the tumor itself.
In recent years, several new techniques have emerged for the treatment of very low rectal cancer with the aim of preserving the continuity of the GI (digestive tract) and improving oncologic outcomes and functional results. This article will describe these new techniques and the improvements in oncologic and functional outcomes that are supported by the data.
Intersphincteric resection (ISR)
1. Patient selection
Patient selection is based on MRI, CT, endoanal ultrasound, rigid rectoscopy, and fingerprick findings. In particular, the examination under anesthesia is important to assess the tumor activity, the relationship between the tumor and the perianal sphincter, and the final decision on the surgical procedure. A recent review suggests that ISR should be used for T1-3 tumors within 30-35 mm of the anal verge, with or without invasion of the internal anal sphincter (IAS).
Absolute contraindications to ISR are T4 tumors, extra-anal expansion muscle (EAS) invasion, fixed tumors on finger examination, poorly differentiated tumors, poor preoperative expansion muscle function, distant metastases, and the presence of psychiatric disease.
2.Surgical technique
ISR, first proposed by Dr. Schiessel in 1994, is a resection along the anatomic plane between the IAS and the EAS with the aim of increasing the retention of the sphincter and avoiding a permanent stoma in low-grade rectal cancer.
The procedure consists of two parts: abdominal and perineal. The abdominal procedure begins with separation of the peritoneum over the inferior mesenteric vessels, separation of the left colonic mesentery from the fascia, and exposure of the left colonic artery followed immediately by high ligation of the inferior mesenteric vein and inferior artery. After ligation of the vessels, the peritoneal folds around the sigmoid colon and rectum were separated, the sigmoid mesentery, rectal mesentery and fascia were separated, and resection continued along the rectal mesenteric plane. Sometimes it is also necessary to free the splenic flexure of the colon.
After separation of the mesenteric fascia, the left colonic mesentery, sigmoid mesentery and rectal mesentery are removed and the fascial integrity of the specimen is removed, as well as the lymph nodes to the greatest extent possible. Laparoscopic, open and robotic resections are all available for abdominal resections.
Perineal resection requires the patient to be placed in a high lithotomy position with a self-fixing puller to expose the perineum. 1 mg of epinephrine dissolved in 20 mL of saline is injected at multiple points into the submucosa of the anus to reduce bleeding and facilitate interdigital resection. The anal mucosa is incised circumferentially, at least 1 cm distal to the T1 tumor and 2 cm to the T2-3 tumor, in order to remove the entire rectal wall and part/all of the IAS (Figure 1). A purse-string suture closes the anus to stop the tumor cells from diffusing through the perineum.
The resection is continued under direct vision along the gap of the dilator muscle towards the cephalic end to meet the abdominal TME plane, and the specimen is usually removed transanally. A recto-anal anastomosis is then performed to restore GI continuity. There are various types of anastomoses such as J-pouch, T-pouch or direct coloanal anastomosis, the choice of which is largely based on the surgeon’s personal preference. Finally, a rerouted colostomy or ileostomy is performed.
There are three types of ISR: partial, subtotal and total, differentiated by the extent of IAS resection. Partial ISR is resection of the upper third of the IAS, subtotal ISR is resection of two-thirds of the IAS, and total ISR is complete resection of the IAS. combined resection of the EAS is sometimes used when the tumor may have invaded the intersphincteric or external dilator muscle. ISR differs from traditional colorectal anastomosis after super-low anterior resection because ISR is characterized by resection of the internal dilator muscle along the intersphincteric plane.
3. Early postoperative outcomes
The operative mortality rate fluctuates from 0% to 1.7%, and postoperative complications range from 8% to 64%. The main causes of complications are anastomotic leak, anastomotic stricture, fistula formation, pelvic abscess, incisional complications, bleeding, and intestinal obstruction. Anastomotic leak is associated with postoperative anastomotic stricture, cancer recurrence, poor postoperative function, and increased operative mortality.
One meta-analysis showed a cumulative complication rate of 25.8%, anastomotic leak rate of 9.1%, and pelvic abscess rate of 2.4%. Akagi et al. reported a 12% complication rate and 5.6% anastomotic leak rate for Dindo grade II, while Saito reported a 10% anastomotic leak rate.
4. Oncological results
Tilney and Tekkis identified oncologic outcomes after ISR through a literature search, with 9.5% local recurrence, 81.5% mean 5-year survival, and 9.3% distant metastases. Martin et al. reported that negative distal margins required a mean of 17.1 mm, 96% of patients had a negative CRM margin, and 97% had R0 resection; with a median follow-up of 56 months, total local recurrence was 6.7%, 5-year disease-free survival was 78.6%, and 5-year overall survival was 86.3%.
A large prospective study enrolling 124 patients with low-grade rectal T1-3 tumors without preoperative chemoradiotherapy (CRT) was published in 2013. The results showed an overall postoperative recurrence rate of 16.1%, local recurrence of 4.8%, lateral lymph node metastases of 2.4%, pelvic floor recurrence in 2.4% of patients, and distant metastases of 10.5%; comparing the oncologic results of contemporaneous ISR and APR, the overall recurrence-free survival and local recurrence rates after ISR were similar to those of APR.
In Saito’s prospective study, 199 patients were recruited and treated with ISR, 25% received neoadjuvant CRT, and 20.6% underwent concomitant EAS resection. At a median follow-up of 6.5 years, 14.1% had lung metastases, 13.6% had local recurrence with or without distant metastases, 7.5% had liver metastases, and 4.5% had multiple recurrences. Positive CRM was 19.6%, with expected 7-year overall survival, disease-free survival and local recurrence-free survival of 78%, 67% and 80%, respectively. However, T4 tumors were included in this study.
Most studies comparing LAR, APR and ISR concluded that oncologic outcomes were not significantly different, except for Saito, who reported worse 5-year overall survival for APR than for ISR. 77, 68 and 33 patients were in the ISR, LAR and APR groups, respectively, with no significant differences in overall recurrence, local recurrence and 5-year local recurrence-free survival between the groups. 76.4% 5-year overall survival in the ISR group was better than 51.2% in the APR group and similar to 80.7% in the LAR group. This may be related to the fact that there were more patients in the APR group with progressive disease.
According to TNM staging, the 5-year overall survival was 90.0%, 79.8% and 65.6% for stage I, II and III patients in the ISR group, respectively; the 5-year overall survival for stage III patients in the ISR, LAR and APR groups was predicted to be 65.6%, 56.3% and 33.3%. These long-term results suggest that the oncologic outcome of ISR is very good. However, T3 tumors and margin-positive patients are more likely to experience local recurrence after ISR.
CRM was a very strong predictor of local recurrence, with positive CRM patients having significantly worse overall survival, disease-free survival, and local recurrence-free survival than CRM-negative patients. Other factors contributing to local recurrence included undifferentiated tumors, preoperative CA199 above 37 U/mL, and pathologically poorly differentiated tumors with N1 or N2 lymph nodes.
5. Functional outcome: quality of life
Postoperative anal function is an important marker of clinical outcome in dilator preserving surgery for low rectal cancer, but only a few studies have reported short-term postoperative outcomes. resting anal pressure after ISR does not fully recover rapidly and needs to be gradually restored; maximum squeeze pressure is not affected. In conclusion, anal function needs to improve gradually over time.
Köhler et al. reported a 29% reduction in resting anal pressure after ISR, with squeeze pressure returning to preoperative levels 12 months after surgery; Martin reported an average of 2.7 bowel movements per day, with nearly half of patients having normal bowel movements, 1/3 having fecal incontinence, 23.8% having gas incontinence, and 18.6% having urgency; Denost et al. reported half of patients functioning well, 39% having mild fecal incontinence, and 11% having severe fecal incontinence. Saito et al.
Saito et al. reported long-term functional outcomes in 199 patients with a bowel movement of 4.0±3.7/day and a median Wexner score of 8.5 at 5 years after fistula closure, with approximately 50% having fecal interruption, gas incontinence, 30% having fecal incontinence, and ¼ having difficulty emptying. In men, preoperative CRT was a predictor of poor bowel control, and type of surgery did not affect long-term functional outcomes. the Ito report also supports that preoperative CRT has the greatest impact on anal function, while the Yamada study showed that patient age at the time of surgery was the only postoperative risk factor for fecal incontinence.
Denost et al. reported that risk factors for fecal incontinence after ISR were directly related to tumor level and anastomotic height, and that to obtain good bowel control, the tumor needed to be more than 1 cm from the anorectal loop and the anastomosis more than 2 cm from the anal verge.
A recent study comparing functional outcomes after ISR and LAR found that postoperative defecation function such as frequency of defecation, presence of urgency, differentiated venting and perianal skin itchiness were similar in both groups, with lower Wexner scores in the LAR group, but no difference in fecal incontinence quality of life scores (FIQL) between the two groups.
Bretagnol et al. used the SF-36 and FIQL questionnaires to compare quality of life (QoL) in patients with ISR and conventional colorectal anastomosis and did not find differences in physical and mental scores between the two groups. saito et al. reported that patients with ISR with or without EAS resection were in better or equal status at 5 years, whereas patients with preoperative CRT showed a significant decrease in FIQL quality of life scores at long-term follow-up.
6. Conclusion
ISR is an alternative to the classical surgical approach for the treatment of low-grade rectal cancer. The literature shows that ISR is indicated for T1-3 tumors, located 30-35 mm within the anal verge, with or without IAS invasion, with comparable oncologic outcomes to LAP and APR, and acceptable quality of life.APR can be used for locally progressive tumors.