TaTME Versus Open Intersphincteric Resection After Neoadjuvant Concurrent Chemoradiotherapy.

Study Overview
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Brief Summary
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The two surgical options for lower 1/3 rectal cancer is APR and sphincter sparing procedures. Intersphincteric resection is procedure to treat very low rectal cancer within 2 cm from the dentate line to avoid permanent colostomy,improves the quality of life with better genitourinary function. Neoadjuvant chemo-radiotherapy is routine for T3 cases.

Detailed Description
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During the period between April 2013 and July 2019, a non-randomized controlled study was performed at two tertiary centers; Oncology Centre of Mansoura University and Policlinico Umberto Primo surgery department of SAPIENZA university of Rome after referral from the clinical oncology and nuclear medicine department. After diagnosis of ultralow rectal cancer, a written informed consent was obtained from patients after full explanation of the procedure, the likely outcome and the potential complications that may occur. Digital rectal examination was conducted to assess the distance of lower tumor margin from the anal verge and the anal tone. Anesthetic fitness and tumour markers (CEA) were assessed. Pelvis MRI and/or endorectal ultrasound (EUS), abdomen and chest CT scan and colonoscopy with biopsy were done for all cases. Re-evaluation after neoadjuvant chemo-radiotherapy by MRI and EUS. Inclusion criteria included a very low rectal cancer below 5 cm from the anal verge with normally continent and tumor-free external anal sphincter. Neoadjuvant treatment was given to all patients with T3 or node positive tumors. Exclusion criteria were T4, metastatic tumors and fecal incontinence. Fifty patients were excluded from the study (Fig.1). One hundred and ten patients with ultralow rectal adenocarcinoma, with matched age and sex (table 1), were non-randomly classified into two equal groups: the control group included 55 patents that underwent sphincter sparing by open ISR with TME (O-ISR Group) and the 2nd group included 55 patents that underwent Transanal minimally invasive ISR with TME (TAMIS Group). Surgical technique: In open ISR, the inferior mesenteric vessels were highly ligated. After full mobilization of the left colon and splenic flexure was done, the plane for TME was followed down in the pelvis superficial to the hypogastric fascia as low as possible to enter into the posterior intersphincteric plane. A non-endoscopic perineal phase was then initiated using an anal lone-star retractor to expose the anal canal. Both the mucosa and the muscular layer were incised 1cm below the tumor margin to transect the internal anal sphincter (IAS) and then closed by purse string sutures. The dissection continued between IAS and the external anal sphincter (EAS) starting posteriorly then laterally, where EAS is easier to identify, then anteriorly where the plane presented more adhesions with the urethra in male or vagina in female till reaching the abdominal dissection. Proximal division of the specimen started just below the site of inferior mesenteric vessels ligation and continued till division of the marginal artery at the site of the required anastomosis. The Specimen extraction and division was done extra-anal. A defunctioning ileostomy was done in all cases. In TAMIS-TME, using a lone star retractor, the 1st step was to divide and close the anal canal by purse-string suturing to enter the intersphincteric plane. Using TEo platform (Karl Storz, Tuttilingen, Germany) (fig. 2) with a 4 cm size operating proctoscope diameter, Transanal endoscopic dissection was initiated and continued in the intersphincteric plane starting posteriorly then laterally. Partial or high ISR started at the dentate line to remove the upper half of IAS for ultralow tumors at 3 to 4.5 from anal verge. Total or low ISR started 1 cm below the dentate line, removing the whole of IAS for tumours below 3 cm from the anal verge. The endoscopic dissection continued in the same sequence as the control group along the levator ani. Then continue posteriorly till reaching as much as possible, then dissection continued laterally and anteriorly to reach the peritoneal reflection. Then, the laparoscopic phase was initiated to ligate the inferior mesenteric vessels and mobilize the splenic flexure and left colon. The peritoneal reflections were then divided to connect to the transanal part. The specimen was then extracted transanally and the Colo-anal anastomosis was done in two layers. A defunctioning ileostomy was done in all cases.

Official Title
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Transanal Minimally Invasive TME (TaTME) Versus Open Intersphincteric Resection and Total Mesorectal Excision of Stage II/III Ultralow Rectal Cancer After Neoadjuvant Concurrent Chemoradiotherapy.

Conditions
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Rectal Cancer

Intervention / Treatment
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* Procedure: Open intersphincteric resection
* Device: transanal minimally invasive intersphincteric resection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with low rectal carcinoma(The lowest margin of tumor located 3 cm from anal verge ; ≤ 2 cm from dentate lines; 1 cm from anorectal rings. Local spread restricted to the rectal wall or the internal anal sphincter. Adequate preoperative sphincter function and continence. Absence of distant metastasis. Exclusion Criteria: Contraindications to major surgery and American Society of Anesthesiologists (ASA) Physical Status scoring 4. Metastatic rectal cancer. Those in Dukes stage D (T4 lesion). Undifferentiated tumours. Local infiltration of external anal sphincter or levator ani muscles. Tumor located more than 2 cm above the dentate line. Presence of fecal incontinence. Patients unwilling to take part in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Open intersphincteric resection<br>surgical Instruments for open approach intervention: Open laparotomy through abdominal incision and mobilization of the colon and rectum up to the splenic flexure with high ligation of the inferior mesenteric vessels and mesorectal excision till the levator ani then the peranal approach to resect the distal margin of the rectum through high or low intersphincteric resection in the plane between internal and external anal sphincters. | Procedure: Open intersphincteric resection<br>* laparotomy arm: surgical Instruments for open approach operation: Abdominal anterior resection combined with peranal intersphincteric resection of the rectum Abdominal step a high ligation of the inferior mesenteric artery is performed together with a full mobilization of the left colon. A circular incision of the anal canal is performed 1 cm below the tumour. Both the mucosa and the muscular layer are incised to transect the internal anal sphincter. A coloanal anastomosis, transverse coloplasty or colonic J-pouch and a diverting loop ileostomy are associated with the hand-sewn coloanal anastomosis. laparoscopic approach group: instruments used: laparoscopic instruments mentioned at the arm description intervention: laparoscopic mobilization of the rectum and colon combined with the peranal intersphincteric resection as in the laparotomy approach<br>* Other names: interspincteric resection;|
| Active Comparator: laparoscopic intersphincteric resection .<br>instruments used: 4 or 5 laparoscopic trocars (two or three (10-mm) trocar, Two 5-mm trocars and a 12-mm trocar with reducers),Three 5-mm fenestrated grasping forceps, Five-millimetre coagulating shears, a 5-mm straight grasping forceps, Harmonic scalpel, 5 or 10 mm, a 10-mm fenestrated forceps, a 10-mm dissector,5 mm Bipolar grasper, a 5-mm needle holder, Twelve-millimetre linear staplers intervention: Trocar Placement and Exposure Rectosigmoid Mobilization and Control of Inferior Mesenteric Vessels Taking Down the Splenic Flexure rectal dissection till the levator ani muscle and resection of thye lateral ligaments then the peranal phase as in the laparotomy approach. | Device: transanal minimally invasive intersphincteric resection<br>* minimally invasive approach group: instruments used: laparoscopic instruments mentioned at the arm description instruments: laparoscopic instruments mentioned in the laparoscopic rectal resection arm intervention: laparoscopic mobilization of the rectum and colon combined with the peranal intersphincteric resection as in the laparotomy approach<br>* Other names: lTAMIS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Early Complications number |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of the intervention | Duration of surgery | 1 day | 
| Amount of blood loss and rate of blood transfusion | Amount of blood loss and blood transfusion through the operation | 1 Day | 
| conversion rate for open ISR |  | 1 day | 
| The onset of intestinal motility. | the onset of the intestinal motility guided by (the onset of borborygmus and its sequence, time to give off flatus, time to intake liquid and solid food) | 2 weeks | 
| Pain score | Recording of the needed analgesia guided by pain score | the first two weeks in the postoperative period | 
| Postoperative hospital stay | Outcome observers will assess the hospital stay days after both procedures | 30 Days | 
| 30 days follow up for re-operation in the postoperative period | readmission within 30 days after patient discharge | 1 month | 
| Late complications |  | 2 years | 
| Local recurrence within 2 years | The patients will be observed after the operation for 2 years for local pelvic recurrence | 2 years | 
| Distant metastasis within 2 years | Distant metastasis after the opertaion for 2 years | 2 years | 
| Clinical functional outcome | Investigators will assess the continence using Per Anal Scoring System (PASS) from 0 to 4 | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sphincter sparing procedures, intersphincteric resection, rectal cancer, ultralow rectal cancer, sphincter preserving procedures, Abdominoperineal resection, Trans-anal minimally invasive surgery, TAMIS versus open colorectal resection, neoadjuvant chemo-radiotherapy for rectal cancer