Symptoms and General Pathology

All Conditions

Neoplasms

Digestive System Diseases

Anastomotic Leak

Rectal Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Intestinal Diseases

Rectal Diseases

Postoperative Complications

Hongwei Yao, M.D.

Jun Li, M.D.

Anastomotic leakage (AL) is one of the most-feared postoperative complications after anterior resection of rectal cancer. This complication compromises both short term and long term outcome of patients. The incidence of AL after anterior resection was approximately 6-11%. Although several risk factors for AL such as male sex, smoking, tumor location, longer operative time, intraoperative blood loss had been reported in previous studies, the incidence of AL did not meet a significant decrease. So far there is no multi-site observational study on incidence and risk factors of AL after anterior resection in China, therefore this study aims to work on this issue and provide evidence for clinical practice.

Anastomotic Leakage After Anterior Resection of Rectal Cancer

The Incidence and Risk Factors of Anastomotic Leakage After Anterior Resection of Rectal Cancer: a Multi-site Observational Study

Anastomotic leakage is defined as a defect of the intestinal wall integrity at the colorectal anastomotic site leading to a communication between the intra- and extraluminal compartments.

Beijing Friendship Hospital

Department of General Surgery

Behaviors and Mental Disorders

Syndrome

Low Anterior Resection Syndrome

Colonic Diseases

Quality of Life

Patient suffering from LARS as identified through LARS questionnaire

The distance from anal verge, preoperative radiotherapy and presence of stoma were analysed

anterior resection

Svetlana Doris Brincat

This study adds to the understanding of the contributing factors leading to LARS, the long term effects of this syndrome post-operatively and its impact on quality of life.

Contributing Factors to Anterior Resection Syndrome and Its Impact on Quality of Life: A Retrospective Cohort Study

Incidence of LARS in patients who had anterior resection

Variable factors which might have contributed to LARS were the following:

* Age
* Gender
* Diabetes mellitus
* Pathological stage
* MRI stage
* Distance from anal verge
* Surgical technique
* Preoperative radiotherapy
* Preoperative chemotherapy
* Postoperative radio/chemotherapy
* Type of anastomosis
* Presence of stoma
* Interval from stoma reversal
* Duration of follow-up

The association between LARS and quality of life was assessed.

University of Malta

Surgical trainee

Carcinoma

Adenocarcinoma

Neoplasms, Cystic, Mucinous, and Serous

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma, Mucinous

Low Rectal Cancer defined on MRI as a cancer within 6cm of the anal verge

Gina Brown

Brendan Moran

The MERCURY Study demonstrated the accuracy, feasibility and reproducibility of Magnetic Resonance Imaging (MRI) to stage rectal cancer in a prospective, multidisciplinary, multi-centre study. However, there were differences in patient outcome, dependent upon the position of the tumour in the rectum and its height above the anal verge. Whilst the outcome was excellent for patients who underwent an anterior resection, the outcome, based upon margin involvement and quality of the specimen, was poor for patients who underwent an abdomino-perineal excision for low rectal cancer.

It is proposed that accurate MRI staging pre-operatively will allow the correct patients to receive neo-adjuvant chemoradiotherapy (CRT), and also pre-warn the surgeons if the resection margins appear threatened so that the operation can be modified to take this into account. The primary aims of the Low Rectal Cancer Study (MERCURY II) are to assess the rate of CRM positivity rate in low rectal cancer and to assess the difference in global quality of life at two years post surgery in patients according to plane of surgery with or without sphincter preservation.

The aim of this study is to reduce the positive margin rate of 30% to around 15%. The study is an international multicentre, prospective, observational study, whereby patients with biopsy-proven low-rectal cancer (lower edge of the tumour \< 6cms from the anal verge on MRI), will be recruited from participating centres, having given informed, written consent. Data from the radiology, surgical and pathological aspects will be collected and analysed centrally at the Royal Marsden Hospital. The patient's medical records will be reviewed for five years post surgery, and the patients will also be followed up by quality of life questionnaires. This project aims to show that in low rectal cancer, improved local control and survival can be achieved through a reduction in the involved CRM rates by MRI-planned surgery and selective pre-operative therapy. It also aims to assess the ability to predict disease recurrence and to provide an assessment of disease-free survival and overall survival.

Low Rectal Cancer Study (MERCURY II)

The Low Rectal Cancer Study.

Pelican Cancer Foundation

Royal Marsden NHS Foundation Trust

In High tie group, IMA was transected at its origin from the abdominal aorta.

In the low tie of the IMA, IMA was separated after branching to the left colic artery. The lymph node dissection around the IMA at its origin was performed.

High tie of IMA

Technique for preserving left colic arterial perfusion

Low tie of IMA

Chikara Kunisaki, Professor

The tying at a radix of the inferior mesenteric artery (IMA) is recognized as radical cure technique in a rectal cancer surgery in Japan. In one side, the preserving the left colic artery (LCA) that is the technique to maintain blood flow of proximal sigmoid colon is performed in practice. However, there is no evidence that shows effectiveness of this technique.

We conducted a randomized trial that compared between high tie and low tie of the IMA in rectal anterior resection to define an appropriate portion of IMA tying.

Patients

* This was a randomized controlled trial conducted at a single institute, which was Yokohama City University Medical Center (Japan).
* 300 patients who underwent anterior resection for rectal cancer were randomly allocated to receive high tie or low tie of the inferior mesenteric artery.

Surgical procedures

* All surgical procedures were performed by one specialized colorectal treatment team. The laparoscopic surgeries were performed by a surgeon who passed the skill accreditation system for laparoscopic gastroenterological surgery was established by the Japanese Society for Endoscopic Surgery (JSES), and all open surgeries were performed under the supervision of these skillful surgeons.
* All operations were performed according to the standard radical cure procedure described in the seventh edition of the Japanese General Rules for Clinical and Pathological Studies on Cancer of the Colon, Rectum and Anus. That is, intestinal excision with lymph node dissection around the IMA at its origin was performed in all surgical procedures. Patients who underwent palliative partial excision were not included.
* In the high tie (HT) of the IMA, IMA was separated at its origin from the abdominal aorta.
* In the low tie (LT) of the IMA, IMA was separated after branching to the left colic artery. The lymph node dissection around the IMA at its origin was performed.

Randomization - To balance the operative backgrounds between HT and LT groups, the patients were stratified by the approach of surgery (open or laparoscopic surgery).

Adjuvant therapy

* When the pathological stage was diagnosed as stage 3 by histological examination of the resected specimen, adjuvant chemotherapy was done with oral fluoropyrimidine anti-cancer drug.
* Neither radiation therapy nor preoperative chemotherapy was given to any patient. Preoperative chemo-radiotherapy even for rectal cancer is not yet standard treatment in Japan.

Assessment parameters

* The preoperative parameters
* Operative assessment parameters
* Postoperative assessment parameters An early postoperative complication was defined as a complication that occurred between the finish of the operation and postoperative day 30. A late postoperative complication was defined as a complication that occurred after postoperative day 30. The terminologies of complications were classified according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, and grading was done by Classification of Surgical Complication.
* The pathological results were recorded according to the 7th edition of the Japanese General Rules for Clinical and Pathological Studies on Cancer of the Colon, Rectum and Anus and 7th edition of primary tumor, regional nodes, metastasis (TNM) classification. Circumferential margin involvement was defined as exposure of a cancer cell at the vertical dissection surface on histological examination.

Follow-up schedule

- The follow-up schedule was as follows according to stage. Patients with stages 0 and 1 were followed up with outpatient examinations including tumor marker measurements, and chest, abdominal and pelvic computed tomography (CT) once a year for five years. Patients with stage 2 and 3a were examined by CT and tumor marker measurements every six months for the first two years. These examinations were done once a year from the third year to the fifth year. Patients with stage 3b and 3c were examined by CT and tumor marker measurements every four months for the first two years, and every six months from the third year to the fifth year.

Statistical analysis

* The primary endpoint was anastomotic leakage rate.
* The secondary endpoints were operation time, amount of bleeding and 5-year overall survival. To evaluate whether a difference in the operative procedure influences survival including death due to another disease, a comparison of overall survival has meaning. Operation time and amount of bleeding were added to the secondary endpoints because these parameters had a possibility of becoming grounds of selection of the operation method if there were no differences in overall survival.
* A sample size of 284 patients was assured to achieve a power of 70% to detect a difference between the groups using a two-sided Chi-squared test with type I error rate equal to 0.05, when the true complication rates were 4% and 12% for the LT and HT groups, respectively. A sample size of 300 patients was assured to achieve a power of 73% to detect a difference in a same condition. The dropouts were considered and the number of accumulation targets was assumed to be 300 patients to keep a power of more than 70%.
* For continuous variables, data are presented as means ± standard deviation (SD). For categorical variables, data are presented as frequencies and percentages (%). Comparison of the endpoints was based on intention-to-treat principle, that is, the patients who switched to another group during surgery were treated as members of the allocated group. The Chi-squared test was applied to evaluate the significance of differences in proportions, and t-test was used to evaluate the significance of differences in continuous variables. A p-value of less than 0.05 was considered to be statistically significant.

Randomized Controlled Trial to Evaluate High Tie Versus Low Tie of the Inferior Mesenteric Artery in Anterior Resection

Randomized Controlled Trial to Evaluate High Tie Versus Low Tie of the Inferior Mesenteric Artery in Rectal Anterior Resection for Rectal Cancer Patients

Anastomotic leakage rate is defined as an incontinuity at the anastomosis using circular stapler.

All death is defined as an event of overall survival.

Shoichi Fujii, MD, PhD

Associate Professor

LARS score questionnaire is filled by the patient after anterior resection for rectal cancer to study the quality of life

LARS score questionnaire

Reham Zakaria, PhD

Sphincter sparing surgery is oftentimes associated with bowel dysfunction complaints, namely the low anterior resection syndrome (LARS). The LARS questionnaire is widely used to assess this syndrome.

With advances in colorectal surgery, sparing sphincter surgeries are gaining popularity. But symptoms after surgery can affect the quality of life which has psychomotor effects. Low anterior resection syndrome score is a worldwide known questionnaire. Many countries have accredited validation and translation of this questionnaire, but to our knowledge; it is the first time in Egypt.

Incidence and Risk Factors of Low Anterior Resection Syndrome

Incidence, Risk Factors Of Low Anterior Resection Syndrome And Validation Of LARS Score Among Egyptian Patients

IPD will be shared with other researchers on demand by e- mailing the principle investigator

age of the patients in years was recorded from patient records

sex of patients was recorded from patient records

medical disease like diabetes and hypertension was recorded from patient records

tumor site was determined in Cm from anal verge by colonoscopy

history of neoadjuvant therapy before surgery was obtained from patients records

site of anastmosis after resection was recorded as colo-rectal or colo-anal

excision of meso-rectum was recorded if it was partial or complete

it was recorded from patients records if he\\she had chemo- or radiotherapy post-operatively

from records; surgery was open or laparoscopic

type of anastmosis(hand sewen or stappled) obtained from records

obtained by LARS questionnaire filled by the patient during follow up, it was formed of five questions with different scores on answer choices, interpretaion (0-20) means no LARS, (21- 29) means minor LARS, (30-42) means major LARS

Zagazig University

Principal Investigator

Herbal and Botanical

All Drugs and Chemicals

Cola

With randomisation to this experimental arm (selective approach), no defunctioning stoma is constructed.

With randomisation to this control arm (systematic approach), a defunctioning stoma is constructed using the marked stoma site. A loop ileostomy is fashioned using an ileal loop close to the ileocecal valve, while a loop colostomy can be derived from either the transverse or a redundant left colon.

selective approach defunctioning stoma

Caroline Nilsson, RN

Pamela Buchwald, MD PhD

Martin Rutegård, MD PhD

The goal of this observational trial with a nested randomized controlled trial is to investigate a selective approach of defunctioning stoma in low anterior resection in rectal cancer patients. The primary outcome is a hybrid so-called textbook outcome; stoma-free survival at two years without major LARS, reflecting a functionally appropriate outcome after low anterior resection for rectal cancer. Secondary outcomes include anastomotic leakage, postoperative mortality, reinterventions, stoma-related complications, quality of life measures, LARS, and permanent stoma rate up to two years after index surgery.

Systematic use of defunctioning stoma after low anterior resection for rectal cancer has been shown to reduce symptomatic anastomotic leakage and associated interventions. However, accumulating data suggest that this comes at the price of worse bowel dysfunction, a higher rate of permanent stomas and kidney injury. We aim to study whether a selective strategy of defunctioning stoma use might lead to fewer adverse consequences, while still being safe for patients.

This is a multicentre international prospective trial including a non-blinded randomised clinical trial. All patients with a primary rectal cancer planned for low anterior resection with colorectal or coloanal anastomosis are eligible. Patients enter a prospective observational study, in which a randomised clinical trial is nested. Patients eligible for randomisation are aged below 80 years, have an American Society of Anesthesiologists' fitness grade I or II, have no unresected distant disease, and have a predicted lower risk of anastomotic leakage. Patients will be randomised 1:1 to either an experimental arm with no defunctioning stoma or to a control arm with a defunctioning stoma. The randomisation is computer-generated with a concealed sequence and stratified by participating hospital and radiotherapy use. The main outcome is the composite measure of 2-year stoma-free survival without major low anterior resection syndrome (LARS). Secondary outcomes include anastomotic leakage, postoperative mortality, reinterventions, stoma-related complications, quality of life measures, LARS, and permanent stoma rate up to two years after index surgery. To be able to state superiority of any study arm regarding the main outcome, with 90% statistical power and assuming 25% attrition, we aim to enrol 212 patients.

This study has been approved by Ethical Review Authority in Sweden (2023-04347-01) and seeks permission in Norway and Danmark, respectively. The results will be disseminated through patient associations, popular science, the broader medical community, and conventional scientific channels.

Observational trial with nested randomized trial

Selective Defunctioning Stoma in Low Anterior Resection for Rectal Cancer

SELective Defunctioning Stoma Approach in Low Anterior Resection for Rectal Cancer (SELSA): a Prospective Study With a Nested Randomised Clinical Trial

Unidentified raw data may be shared upon request.

extant stoma, alive, and a LARS score at 30 or lesn has stabilised as well for those without a stoma in situ.

no extant stoma, alive, and a LARS score at 30 or less at the time point two years after the anterior resection.

domain score scale 0-42 points, \>30 points indicate a bad functional outcome i.e. major LARS

EORTC-CR29 domain scores in scales 0-100 points, a high score for the global health status /quality of life represents a high quality of life, but a high score for a symptom scale / item represents a high level of symptomatology / problems.

Difference from baseline in total score 0-150 points, higher value indicating faster recovery

EORTC-C30 domain scores in scales 0-100 points, a high score for the global health status /quality of life represents a high quality of life, but a high score for a symptom scale / item represents a high level of symptomatology / problems.

Umeå University

Lund University

Göteborg University

Ersta Hospital, Sweden

Copenhagen University Hospital at Herlev

Linkoeping University

Oslo University Hospital

Örebro University, Sweden

Skane University Hospital

associate professor, senior consultant surgeon

Patients where it is possible to perform an anterior resection

Patients with locally advanced rectal cancer

Eva Angenete, M.D., Ph.D.

Rectal cancer is a common type of cancer occuring more frequently in men but also common in women. Almost 60% of the patients survive 5-years and the treatment has been continuously developed in the last three decades. The aim of the QoLiRECT study is to increase the knowledge about symptoms, functional impairments, quality of life (QoL) and psychological and socioeconomic burden in an unselected population of rectal cancer patients.

Rectal cancer is more frequent in men than in women and is relatively uncommon before the age of 50. The prognosis for rectal cancer has improved over the last decades2. Almost 60% of all patients survive more than five years, and because of advances in early detection and treatment, this number is expected to increase in the future1. Treatment of rectal cancer varies depending on the stage of the disease at diagnosis. For some patients, operation is the only treatment. For others, surgery is combined with radiotherapy, chemotherapy or both. The two most common operative procedures are the sphincter-preserving anterior resection (AR) and the abdominoperineal resection (APR) - the latter results in a permanent colostomy. Patients with generalised disease at diagnosis receive palliative treatment, which may include chemotherapy and radiotherapy as well as surgery.

Rectal cancer comes with a high risk of local recurrence, i.e. return of the tumour within the pelvis after a presumed curative resection. Local recurrence is difficult to treat and often very painful and distressing for the patient. Some local recurrences will be candidates for second line surgery, as is also true for some distant metastases.

The aim of the QoLiRECT study is to increase the knowledge about symptoms, functional impairments, quality of life (QoL) and psychological and socioeconomic burden in an unselected population of rectal cancer patients. Symptoms such as incontinence, pain, fatigue and impaired sexual function3 are common with this disease. Bodily changes, caused by the treatment or the disease itself, may lead to functional impairments and psychological, social, emotional and economical restraints. Conventional outcome measures such as morbidity and survival reveal little about these things.

Quality of Life in RECTal Cancer - a Prospective Multicenter Cohort Study

Quality of Life in RECTal Cancer - A Study Within the Scandinavian Surgical Outcomes Research Group

It will be evaluated at diagnosis, , i.e. at presentation of a plan for the treatment, at 12 months after start of the treatment, regardless of which, at 24 months after start of the treatment and at 60 months after start of the treatment

and at 12 months, 36 months and 60 monts after diagnosis

will also be assessed at 12 months after start of the treatment, regardless of which, at 24 months after start of the treatment and at 60 months after start of the treatment

and at 12 months after start of the treatment, regardless of which, at 24 months after start of the treatment and at 60 months after start of the treatment

This will be analyzed regardless of which, at 24 months after start of the treatment and at 60 months after start of the treatment

May be another time frame than the one registered. Depends on results from the QoL questionnaire

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Anastomotic Leakage After Anterior Resection of Rectal Cancer	NCT03281070	Rectal Cancer		-	Beijing Friendship Hospital
Contributing Factors to Anterior Resection Syndrome and Its Impact on Quality of Life: A Retrospective Cohort Study	NCT04114591	Low Anterior Re... Cancer Quality of Life	anterior resect...	18 Years -	University of Malta
Anastomotic Leakage After Anterior Resection of Rectal Cancer	NCT03281070	Rectal Cancer		-	Beijing Friendship Hospital
Low Rectal Cancer Study (MERCURY II)	NCT02005965	Adenocarcinoma Adenocarcinoma,... Carcinoma Neoplasms, Glan... Neoplasms by Hi... Neoplasms Neoplasms, Cyst... Colorectal Neop... Intestinal Neop... Gastrointestina... Digestive Syste... Neoplasms by Si... Digestive Syste... Gastrointestina... Intestinal Dise... Rectal Diseases		18 Years -	Royal Marsden NHS Foundation Trust
Randomized Controlled Trial to Evaluate High Tie Versus Low Tie of the Inferior Mesenteric Artery in Anterior Resection	NCT01861678	Rectal Cancer Colon Rectal Re...	High tie of IMA Low tie of IMA	20 Years -	Yokohama City University Medical Center
Incidence and Risk Factors of Low Anterior Resection Syndrome	NCT06359730	Colorectal Canc...	LARS score ques...	18 Years - 60 Years	Zagazig University
Selective Defunctioning Stoma in Low Anterior Resection for Rectal Cancer	NCT06214988	Rectal Cancer	selective appro...	18 Years -	Skane University Hospital
Low Rectal Cancer Study (MERCURY II)	NCT02005965	Adenocarcinoma Adenocarcinoma,... Carcinoma Neoplasms, Glan... Neoplasms by Hi... Neoplasms Neoplasms, Cyst... Colorectal Neop... Intestinal Neop... Gastrointestina... Digestive Syste... Neoplasms by Si... Digestive Syste... Gastrointestina... Intestinal Dise... Rectal Diseases		18 Years -	Royal Marsden NHS Foundation Trust
Quality of Life in RECTal Cancer - a Prospective Multicenter Cohort Study	NCT01477229	Rectal Cancer Quality of Life Surgery		18 Years -	Sahlgrenska University Hospital, Sweden
Quality of Life in RECTal Cancer - a Prospective Multicenter Cohort Study	NCT01477229	Rectal Cancer Quality of Life Surgery		18 Years -	Sahlgrenska University Hospital, Sweden

Spots Global Cancer Trial Database for anterior resection