Clinical trial NCT06662643: A Clinical Trial Comparing Staged Turnbull-Cutait Pull-through Anastomosis With Direct Anastomosis Plus Prophylactic Ileostomy in the Treatment of Low Rectal Cancer After Internal Sphincter Resection
Official title: A Prospective, Multicenter, Randomized Controlled Clinical Trial Comparing Staged Turnbull-Cutait Pull-through Anastomosis With Direct Anastomosis Plus Prophylactic Ileostomy in the Treatment of Low Rectal Cancer After Internal Sphincter Resection
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Rectal Cancer
Rectal Carcinoma
Keywords: Low Rectal Cancer
Turnbull-Cutait
Pull-through
Internal Sphincter Resection
Lead sponsor: Zhongnan Hospital
Sponsor class: OTHER
Collaborators: name: Ezhou Central Hospital
name: Jingzhou Central Hospital
name: Taihe Hospital
name: Hubei University of Medicine
name: Qilu Hospital of Shandong University
name: Beijing Chao Yang Hospital
name: Tianmen First People's Hospital
name: Xiangyang Central Hospital
name: First People's Hospital of Xianyang
name: Central Hospital of Xiaogan
name: Yichang Central People's Hospital
name: Yichang Second People's Hospital
name: Rocket Force Special Medical Center of the People's Liberation Army
name: Huashan Hospital
First posted: 2024-10-29
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study targets patients undergoing ultra-low rectal cancer surgery, which requires internal sphincter resection for sphincter-saving procedures. The study compares the staged Turnbull-Cutait Pull-through anastomosis (a delayed transanal pull-through anastomosis without a protective stoma) as the experimental group with traditional anastomosis (hand-sewn/stapled) plus protective ileostomy as the control group. The aim is to assess whether the Turnbull-Cutait Pull-through colon-anal anastomosis is non-inferior to traditional ISR surgery in terms of complications (short-term such as anastomotic leakage/dehiscence, pelvic infection, anastomotic bleeding, ischemic bowel necrosis, bowel obstruction, and long-term complications such as anastomotic stricture, perianastomotic fistula, bowel obstruction, stoma-related complications, and others), postoperative anal function, quality of life, long-term oncologic outcomes, hospital stay duration, and total hospitalization costs.

Detailed description: In recent years, with the increasing understanding of the anatomy and physiological functions of the lower rectum, the biological behavior of rectal cancer tumors, advancements in new surgical technologies, and the application of comprehensive treatment methods, there has been growing emphasis on radical surgical procedures for low rectal cancer that balance oncological safety with anal function preservation. After undergoing total mesorectal excision for low rectal cancer and subsequent coloanal anastomosis, patients often face a high risk of anastomotic leakage and pelvic infection. Therefore, a protective ileostomy is usually performed to divert feces, providing a relatively low-perfusion environment conducive to healing for ultra-low coloanal anastomoses. In the event of an anastomotic leak, the protective stoma can mitigate infection and reduce the likelihood of secondary surgeries. Nevertheless, complications following protective ileostomy, such as dehydration, chronic renal failure, and parastomal hernia, occur at rates as high as 43% . Additionally, complications related to stoma reversal exceed 20% , all of which significantly impact patients' quality of life. Approximately one-fifth of patients with preventive stomas are unable to have their stomas reversed as planned, or may require lifelong stoma formation.

In 1961, Turnbull and Cutait independently reported surgical techniques involving transanal pull-through rectal resection and delayed manual coloanal anastomosis. From a certain perspective, this procedure is the safest reconstructive method, effectively reducing anastomotic leakage-related complications and avoiding the need for a protective stoma. In recent years, its clinical application in challenging rectal cases involving radiation proctitis, complex recto-vaginal/urethral fistulas, salvage surgeries for anastomotic leaks, and low-stage progressive rectal cancer has gained increasing attention and acceptance.In 2020, a multicenter randomized controlled study published in JAMA Surgery found that the delayed anastomosis group (avoiding protective stoma) did not increase the incidence of anastomotic leaks or other complications compared to the standard coloanal anastomosis plus ileostomy group, and exhibited comparable oncological and functional outcomes . Furthermore, a recent systematic review in 2022 included one randomized controlled trial and nine observational studies with a total of 1,743 patients. This study found that staged Turnbull-Cutait anastomosis was associated with a reduced rate of anastomotic leaks.

However, the aforementioned studies and systematic reviews on staged Turnbull-Cutait anastomosis were all based on total mesorectal excision (TME), and there is a paucity of data on postoperative anal function and quality of life following this procedure, necessitating further research. As an extreme sphincter-saving surgery, ISR is currently limited in widespread adoption due to the high incidence of postoperative complications and suboptimal functional outcomes associated with anastomoses located very close to the anal verge. To date, there is a lack of systematic studies applying the Turnbull-Cutait Pull-through anastomosis to ISR procedures. Therefore, it is highly worthwhile to conduct a multicenter prospective randomized controlled study to determine whether the modified Bacon procedure (transanal pull-through, delayed anastomosis) can serve as an effective alternative to ISR-coloanal anastomosis, achieving comparable or lower rates of postoperative complications, as well as equivalent oncological radicality and defecatory function. Such research is urgently needed in this largely unexplored field. If successfully conducted and achieving its objectives, this clinical study could provide highly valuable guidance for clinical practice. Existing reports on the application of the modified Bacon procedure in low rectal cancer are generally small-sample, single-center, retrospective studies with low levels of evidence. This study aims to provide higher-level evidence through a larger-sample, prospective, multicenter, randomized controlled design.

Eligibility criteria: Inclusion Criteria:

1. Histopathologically confirmed high- or moderate-grade adenocarcinoma or villous adenoma with malignancy on preoperative colonoscopy; tumor located ≤ 5 cm from the anal verge; primary tumor size \< 5 cm in diameter.
2. All enrolled patients require intersphincteric dissection. PISR surgery must be completed with hand-sewn (preferably) or stapled coloanal anastomosis. The anastomosis should be located near the dentate line (intraoperative photos or videos must be preserved).
3. Both male and female patients aged 18-75.
4. Non-recurrent rectal cancer.
5. No concurrent multiple primary colorectal cancers.
6. Initial staging or post-neoadjuvant therapy stage: T3 above the levator ani, T1-2 below.
7. Liver or lung oligometastases deemed resectable after evaluation by a multidisciplinary team (MDT).
8. Patients may or may not have received neoadjuvant chemoradiotherapy.
9. Patients and families must understand and be willing to participate in this study, providing written informed consent.
10. Good anal function (Wexner incontinence score ≤ 5).

Exclusion Criteria:

1. History of malignant colorectal tumors.
2. Previous colorectal or anorectal surgeries or diseases.
3. Patients requiring emergency surgery due to intestinal obstruction, perforation, or bleeding.
4. Tumor invasion into the external sphincter, levator ani, or adjacent organs requiring combined organ resection.
5. Poor preoperative anal function or incontinence (Wexner incontinence score ≥ 6).
6. History of inflammatory bowel disease (IBD) or familial adenomatous polyposis (FAP).
7. Recent diagnosis of other malignancies.
8. Participation in other clinical trials within the 4 weeks prior to enrollment.
9. ASA classification ≥ IV or ECOG performance status ≥ 2.
10. Severe hepatic, renal, cardiopulmonary, or coagulation dysfunction or serious underlying disease precluding surgery.
11. History of severe mental illness.
12. Pregnant or breastfeeding women.
13. Uncontrolled preoperative infection.
14. Other clinical or laboratory findings making the patient unsuitable for the study, as judged by the investigator.

Primary outcomes:
measure: 30-Day Overall Composite Postoperative Complication Rate
timeFrame: postoperative 30 days
Secondary outcomes:
measure: Long-term Complications Rate
timeFrame: postoperative 2 years
measure: Total Surgery Time
timeFrame: postoperative 1 years
measure: LARS Score Questionnaire
timeFrame: Every 6 months in the postoperative 3 years
measure: Wexner Incontinence Score
timeFrame: Every 6 months in the postoperative 3 years
measure: International Prostate Symptom Score (IPSS) Questionnaire
timeFrame: Every 6 months in the postoperative 3 years
measure: The Fecal Incontinence Quality of Life Scale (FIQL).
timeFrame: Every 6 months in the postoperative 3 years
measure: International Index of Erectile Function (IIEF-5) Questionnaire
timeFrame: Every 6 months in the postoperative 3 years
measure: Female Sexual Function Index (FSFI) Questionnaire
timeFrame: Every 6 months in the postoperative 3 years
measure: EORTC QLQ-CR29 Questionnaire
timeFrame: Every 6 months in the postoperative 3 years
measure: 3-year Disease-Free Survival (3-year DFS)
timeFrame: postoperative 3 years
measure: 3-year Overall Survival (3-year OS)
timeFrame: postoperative 3 years
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Department of colorectal and anal surgery, Zhongnan Hospital of Wuhan University
state: Hubei
Study officials:
affiliation: Department of colorectal and anal surgery, Zhongnan Hospital of Wuhan University
name: Congqing Jiang, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: La Raja C, Foppa C, Maroli A, Kontovounisios C, Ben David N, Carvello M, Spinelli A. Surgical outcomes of Turnbull-Cutait delayed coloanal anastomosis with pull-through versus immediate coloanal anastomosis with diverting stoma after total mesorectal excision for low rectal cancer: a systematic review and meta-analysis. Tech Coloproctol. 2022 Aug;26(8):603-613. doi: 10.1007/s10151-022-02601-4. Epub 2022 Mar 28.
citation: Biondo S, Trenti L, Espin E, Bianco F, Barrios O, Falato A, De Franciscis S, Solis A, Kreisler E; TURNBULL-BCN Study Group. Two-Stage Turnbull-Cutait Pull-Through Coloanal Anastomosis for Low Rectal Cancer: A Randomized Clinical Trial. JAMA Surg. 2020 Aug 1;155(8):e201625. doi: 10.1001/jamasurg.2020.1625. Epub 2020 Aug 19.
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