Neoplasms

Digestive System Diseases

All Conditions

Colonic Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Herbal and Botanical

All Drugs and Chemicals

Cola

Outcomes will be analysed for the different groups

The extend of lymphadenectomy achieved will be described by a visual analogue scale (VAS) after the operation

The quality of the specimen will be documented postoperatively by a graded classification system

Complications by Clavien Dindo Number of lymph nodes. Disease free and Overall survival

Surgical access

Frank Pfefer, Prof

Havard Forsmo, PhD

Frank Pfeffer, Prof

Aim of the project is to surveil results after extended lymphadenectomy for right sided colon resection for cancer with different operative techniques. Patients operated for right sided colon cancer will be involved. There are different operative methods used in terms of extend of lymphadenectomy and access (open, laparoscopic and robotic assisted) that are already implemented. The Norwegian standard operation contains less extended lymph node dissection. Patients operated by the standard method will serve as control group. Choice of access and extend of lymph node dissection in Norway is dependant on the surgeon and hospital. At Haukeland University Hospital extend and access of surgery are determined by a multidisciplinary team meeting. More radical surgery might result in more complications and the benefit for the patients in terms of oncological result and survival is uncertain. At Haukeland University Hospital, extended lymphadenectomy has been mostly performed by open surgery. During the study phase we will introduce extended lymphadenectomy by laparoscopy and robotassisted surgery. Hypothesis is that more radical surgery performed by minimal invasive surgery will result in equal or better oncological results, and less complications, shorter hospital stay and better quality of life. As method we choose a prospective observational study. All eligible patients with adenocarcinoma of the right colon without another ongoing oncological treatment for other cancers will be included. Patientdata will be prospectively registered in a web-based database. Aim of the study will be to define the optimal extend of lymphadenectomy to achieve the best oncological result. In addition, we will analyse the results dependent on the surgical access (open, laparoscopic or robotic). The assumed difference between the operative methods is small. Therefore, the study is designed and approved as a multicenter registration in order to achieve the necessary statistical power.

Right colectomy for colon cancer database

1. Scientific plan: 1.1. Rationale for the project Colon cancer is the third most cancer in Norway. Five-year relative survival for men and women is 65% and 69% respectively. Surgery is the cornerstone of the treatment and about 50% of patients are cured by surgery alone. In 2018, 2117 patients with stage I-III colon cancer were operated in Norway. About half of them with right-sided colectomies. Parallel to the development of minimally invasive surgery, focus on more radical surgical technique has been increasing, inspired by the improved survival in rectal cancer. Despite growing interest in surgical technique, the level of evidence in this area is low. Reasons are the lack of a common definitions of surgical technique and anatomical differences between the right and left colon. There are two sets of terms used to describe radical colon cancer surgery with adequate lymph node harvest and dissection along embryological planes. The Japanese D2 and D3 dissection refers to lymph node stations and the corresponding European "complete mesocolic excision" (CME) and central vascular ligation (CVL) to anatomical planes. Despite the mentioned uncertainties, there is growing evidence that more radical surgery is leading to improved oncological outcome in right- sided colon cancer. Minimal invasive surgery improves quality of life by reducing pain, postoperative complications and thereby reduces hospital stay and convalescence, but there is concern that more radical surgery is associated with more intraoperative injuries and severe non-surgical complications than "conventional" resection for colon cancer. Robotic assisted right-sided colectomy could overcome the technical challenges of more radical surgery with all benefits from minimal invasive surgery. Introduction of new health technologies may cause serious harm to patients and has to be monitored carefully. In Norway, reporting to the Norwegian Cancer Registry and the Norwegian Registry for Gastrointestinal Surgery is mandatory. But both registries do not cover details of the surgical technique, route of access and quality of the specimen.

1.2. Participating institutions and database solution To date, the applicants have several databases approved by the local ethics committee that cover different topics of colorectal cancer. In order to make the database accessible to a larger cohort we decided to create a web-based solution. From the existing databases, a selection of a maximum of 50 parameters have to be transferred.

The database will be designed as an easy to use, cloud-based solution which enables multiuser and multicenter utility. The database will have filters and include tools for analysis and statistics to facilitate generation of descriptive data to be used for data quality assurance and hypotheses testing. This function will also provide regular reports (i.e. every 6 months) to ensure data quality and patient safety during the introduction of more radical surgery and throughout the study. The web-access functionality of the database went through a risk and vulnerability analysis of the local health care authorities and is approved by "Helse Vest IKT". It will also have the possibility to include patient outcome measures (PROMS) and patient reported experience (PREMS) modules. In order to reach statistical power for some hypothesis (i.e. oncological outcome) we will need a sample size that is too big for a single institution. Therefore, the database will be offered to all Norwegian hospitals operating right-sided colectomies.

1.3. Data collection To have a valid control group, all operations for right-sided colon cancer will be registered, including open, laparoscopic and robotic assisted access. The extend of surgery will be documented according to the Japanese D2 and D3 classification, as D2-, complete D2- and D3 dissection. The quality of the specimen will be assessed by the operating surgeon and pathologist by a newly proposed classification system for right-sided colon cancer. Photo documentation of the anatomy after dissection will give the opportunity to analyse the quality of surgery independently. All data will be recorded prospectively immediately after the operation and after 30 days. Long-term outcomes such as survival, hernia, and recurrences shall be checked 6 monthly. In addition, in order to avoid double data entry oncological results will be collected from the Norwegian Cancer Registry and postoperative complications from the Norwegian Registry for Gastrointestinal Surgery. Merging data from national databases is current practice in Norway and there will be no delay. Ethical committee has approved the study. The patients will be asked for informed consent before data collection. Data can be collected in the web-based database Ledidi (Intraoperative, postoperative form) or paper based. Participating other hospitals will get access to the database after signing a collaboration and data processor agreement.

Health related quality of life (HRQoL) is assessed using the 15D instrument (http://www.15d-instrument.net/15d), a validated, standardized, self-administered health state descriptive questionnaire translated into Norwegian that can be used as a profile and single index score measure.

1.4. Database and security: Ledidi Prjcts is a commercially available web-based software solution developed, approved and used by the Oslo University Hospital (Rikshospitalet). The database has been evaluated for risk and security (ROS) and is approved by the local IT provider "Helse Vest IKT".

Ledidi's security system and Prjct's technical architecture are specified and implemented according to requirements and templates from:

* "Normen" (Information security norm in the Norwegian health care sector)
* General Data Protection Regulation (GDPR)
* Health Insurance Portability and Accountability Act
* Strategy, which is the governing perspective

The developers are constantly working to ensure that the technical architecture and security of the solution complies with the requirements referred to above. Ledidi's information security governance consists of:

* Procedures, protection and technology, which constitute the implementing perspective
* Control, to handle nonconformities, among other things Procedures and technical solutions ensure

  1. data integrity and confidentiality, e.g. through a. encryption upon storage and b. encryption during transport
  2. authentication and authorization, implying that only the right people have the right access
  3. 2-factor authentication at login for further verification of user identity
  4. directly identifiable data is only available to users with the correct access level
  5. protection against denial of service attacks (DoS and DDoS) and other types of attacks.
  6. continuous logging and traceability
  7. redundancy and scaling
  8. deletion and return upon requests
  9. secure storage management
  10. backup and restore

1.5. Study Design This is a prospective comparative study, assessing complications and oncological outcome following all types of colectomy procedures for right-sided colon cancer, at the sponsor institution in the first instance. Open, laparoscopic and robotic assisted operations will be included. Data from all patients undergoing the procedures will be collected for at least 3 years in order to obtain information about eventual start of adjuvant chemotherapy, incidence of hernia and oncological outcome (survival, recurrence).

Other institutions will be offered to collect their colectomy data in the Ledidi database for free.

1.6. Aim of the study The primary aim of the project is to compare the impact of surgical radicality on clinical outcomes for right-sided colon cancer. If sufficient sites participate a large sample size could be achieved (see section 2.8), this will also enable statistical comparison of oncological outcomes.

1.7. Study Endpoints Primary endpoint

* Surgical complications (Patient safety) Secondary endpoints
* Surgical quality (Specimen quality, number of lymph nodes)
* Quality of life after surgery
* Oncological outcome (survival, recurrence, adjuvant therapy) Surgical endpoints
* Operating time (min)
* Conversions
* Intraoperative blood loss/ perioperative transfusion units
* Significant incidents of bleeding from superior mesenteric artery, vein or their branches in the mesentery requiring intervention
* Specimen quality
* Reoperations
* Anastomotic leak
* Prolonged postoperative ileus
* Total length of hospital stay/ readmissions within 30 days
* Incisional hernia at 6 months

1.8. Sample Size In Norway, about 1000 right-sided colectomies are performed annually and about 60-80 scheduled, elective procedures at our institution. At present a randomization between to different procedures with different radicality at a single institution will be unethical if the more radical approach is already implemented. For that reason, non-randomization will be the major bias. This could be overcome by multiple centers that stick to detailed definitions of different procedures (D2, D3, complete D3) as mentioned earlier. With a larger sample size, a propensity score in a case control study could be performed. Another possibility will be to compare the results to historical or national data from the registries.

An improvement from 40% complications (Clavian Dindo grade 2-5)14 to 20% in the robotic group is considered statistically significant. To have a 90% power to detect such a difference a sample size of 218 patients is needed. At our hospital about 60- 80 right-sided colectomies were performed annually. Thus, the estimated total accrual period will be 3 years. Regarding oncological results, to show a 10% improvement in 5 years relative survival between standard lymph node dissection (D2) and extended dissection (D3) with a= 0,05 and power of 0,80 will require 555 patients in each arm.

2. Ethical considerations All surgical techniques are used in clinical practice as recommended and defined by national guidelines. But the distribution of access (open or laparoscopic) and the extend of lymph node dissection varies between the different surgeons and the Norwegian hospitals. At Haukeland University Hospital, open D3 dissection has been performed since 2015 and is currently under evaluation by a randomized trial (REK Ref.nr.: 2015/2396: Open D3 right hemicolectomy compared to laparoscopic CME for right sided colon cancer). The study results are published. Robotic assisted right-sided colectomy with extended lymphadenectomy is performed since 2016. Laparoscopic right-sided colectomy is the standard procedure. Since all operative techniques are implemented, the project should not cause ethical problems. But at present, for operations outside a study protocol, the extend of lymph node dissection for right-sided colectomies is not reported. Though a comparison regarding the extend of lymphadenectomy is not possible.

Right Colectomy for Colon Cancer Database (RCC). Surgical Technique, Route of Access and Quality of the Specimen

Right Colectomy for Colon Cancer Database

All IPDs that underline results in a publication

The primary aim of the project is to compare the impact of surgical radicality on clinical outcomes for right-sided colon cancer. The Clavien Dindo classification is a validated system ranging from I-V.

Specimen quality will be assessed by the surgeon postoperatively by a validated classification system for complete mesocolic excision in right-sided colon cancer (Benz S et al) and the number of lymph nodes

Data will be collected from the patient chart up to 5 years after operation

The QoL questionnaire 15D instrument by Sintonen is a validated self-reported instrument. The 15D is a generic, comprehensive, 15-dimensional, standardized, self-administered measure of health-related quality of life (HRQoL) that can be used both as a profile and single index score measure.

Intuitive Surgical

Haukeland University Hospital

Symptoms and General Pathology

Behaviors and Mental Disorders

Neoplasm Metastasis

Neoplastic Cells, Circulating

Lymphatic Metastasis

Neoplastic Processes

Quality of Life

Right colectomy Open surgery Central lymphadenectomy and vascular ligation

Right colectomy Laparoscopic surgery Central lymphadenectomy and vascular ligation

Open surgery

Right colectomy

Laparoscopic surgery

Central lymphadenectomy and vascular ligation

Kristin B. Lygre, M.D

The primary focus in this study is to investigate and improve the surgical technique. In addition the collection of clinical data during diagnostic and follow up and the collection of tumor and blood gives us the opportunity to investigate tumor biology and its relevance in terms of determine appropriate treatment strategy both surgically and oncological and to assess and predict treatment outcome.

The aim of this study is to compare short and long-term outcomes between open D3 and laparoscopic CME (complete mesocolic excision) with CVL (central vascular ligation) right colectomy for right-sided colon cancer. Our primary hypothesis is that laparoscopic surgery improves quality of life by reducing pain, postoperative complications and thereby reduces hospital stay and convalescence. On the other hand it is to prove non-inferiority of the laparoscopic group compared to the open group by means of oncological outcome (survival, recurrence). Secondary aim is to evaluate surgical quality by comparing actual vascular stump length between the two groups by postoperative CT and compare number of lymph nodes removed with the specimen. With the use of liquid biopsy we want to detect circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) and evaluate their value as tumor markers by comparing the prognostic and predictive value. The hypothesis is that ctDNA and CTCs are more sensitive than standard parameters and imaging (CT CEA).

This is a prospective, randomized, multi-center clinical study. The short term outcome, 2 and 5 year survival and mortality rates will be compared between the groups operated with open D3 resection at Haukeland University hospital and laparoscopic CME with CVL right hemicolectomy at Haraldsplass Deaconess hospital. Computer generated block randomization will be used.

All patients ≤ 85 years with tumor localized in the right colon will be considered to participate in the study. The patients will be summoned to the first consultation to the hospital they are referred to. They will be informed of the study. A patient who meets the inclusion criteria will be asked to participate in the study and sign the informed consent. A patient who accepts will be assigned a sequential participant number and then referred to open D3 or laparoscopic CME (right hemicolectomy) according to a pre-specified randomized list of treatments.

All patients referred with right sided colon cancer in the inclusion period will be registered, and the reason why some do not participate in the study will be documented. Patients who decline to participate in the study will be assigned standard treatment in the institution they are referred to.

Blood samples for analysis of ctDNA/CTCs will be collected preoperatively, 3-10th postoperative day, at 3 months and at each check the next five years at six months intervals. All sample times except the first postoperative control, correspond to the time of CEA and CT in ordinary follow-up. Proteomic technology based analysis of tumor tissue

Open D3 Right Hemicolectomy Compared to Laparoscopic CME for Right Sided Colon Cancer

Open D3 Right Colectomy Compared to Laparoscopic CME Right Colectomy for Right Sided Colon Cancer; an Open Randomized Controlled Study

Incidents of bleeding from central vascular structures; yes/no

Total length of stay, including readmissions within 30 days

Surgical and general complications by Clavien-Dindo Classification og surgical complications

15D Health-related quality of life (HRQoL) preoperative and at 6 months. Scale 0-1. a higher score reflects a better HRQoL

Quality of life (LARS (low anterior resection syndrome) score preoperative and at 6 months. Scale 0-42, where 0 reflects no LARS and 30-42 major LARS.

copies/mL plasma or % fractional abundance (mutant/total ctDNA)

Helse-Bergen HF

University of Bergen

Haraldsplass Deaconess Hospital

Consultant Doctor

Crohn Disease

Inflammatory Bowel Diseases

Gastroenteritis

Benign or malignant disease under going a right colectomy.

Patients with benign or malignant disease under going a right colectomy.

Robotic-assisted or laparoscopic right colectomy with intracorporeal or extracorporeal anastomosis either on or proximal to midtransverse colon.

Right Colectomy

Shilpa Mehendale

The primary objective of this study is to retrospectively compare the perioperative and short-term (discharge through 30 days) outcomes of intracorporeal and extracorporeal anastomosis in minimally invasive right colectomies for benign and malignant disease.

The secondary objective of this study is to retrospectively compare the rates of incisional hernia (up to 6 month post procedure) between intracorporeal and extracorporeal arms.

This is a multi-center, retrospective chart review study of all consecutive cases of right colectomy performed by participating surgeons at their respective institutions that meet all inclusion and exclusion criteria. All cases of right colectomy performed with intracorporeal or extracorporeal anastomoses or via laparoscopic or robotic platforms that meet the study inclusion and exclusion criteria, will be considered for inclusion. The chart review will be performed in a reverse chronological order starting at a minimum of 30 days prior to IRB approval of the study at the site until the number of robotic-assisted and laparoscopic cases to be included per surgeon has been met. Study initiation at the participating site will occur once a research agreement has been executed between Intuitive Surgical and the participating Institution/Investigator and IRB approval has been obtained.

It is anticipated that the retrospective chart review will span the period between January 1, 2010 through 30-days prior to IRB approval of the study in 2016. Baseline patient characteristics, perioperative and post-operative short term clinical and pathological outcomes, and incisional hernia data will be obtained from hospital records for a total of up to approximately 1000 robotic and laparoscopic cases, among the 4 subgroups: robotic-assisted right colectomy with intracorporeal anastomosis (RRCIA), robotic-assisted right colectomy with extracorporeal anastomosis (RRCEA), laparoscopic right colectomy with intracorporeal anastomosis (LRCIA) and laparoscopic right colectomy with extracorporeal anastomosis (RRCEA). Since the data will have been de-identified, and is archival in nature, there will be no active subject recruitment.

Comparison of Intracorporeal and Extracorporeal Anastomoses for Minimally Invasive Right Colectomy

A Multi-Center Retrospective Comparison of Intracorporeal and Extracorporeal Anastomoses for Minimally Invasive Right Colectomy

Number of complications observed intraoperatively through 30-days

Number of complications observed postoperatively through 6 month

Patients will undergo conventional non-CME procedure.

Patients will undergo Right hemicolectomy CME+CVL procedure.

Transecting the Ileocolic Vein and Artery close to the Superior Mesenteric Vessels without clearing the superior mesenteric vein (SMV) from the adipose tissue. Transecting the Right Colic Vein and Artery and superior right colic vein (when present) peripherally. Transecting the Right branches of the Middle Colic Vein (MCV) and the Middle Colic Artery (MCA) peripherally, without clearing the main trunk of the MCV and the MCA. The Right Gastroepiploic Vein and artery are never transacted.

Conventional Right hemicolectomy (Non-CME)

Separation of the visceral fascia from the parietal fascia by sharp dissection leaving intact mesocolon coverage. Transecting the supplying vessels at their origin from the main vessels, particularly:

* The Ileocolic Vessels, The Right Colic Vessels,The superior right colic vein (when present), The Right branches of the Middle Colic Vein and of the Middle Colic Artery
* The MCV and MCA at their origin in case of cancer of the hepatic flexure or of the proximal third of the transverse colon, as well as The Right Gastroepiploic Vessels at their origin from the gastrocolic trunk of Henle (GCTH) and the gastroduodenal artery.

The SMV should be cleared from all adipose tissue all along its anterior surface until its intrapancreatic entrance.

Right hemicolectomy with CME+CVL

Mario Solej, MD

Hogla Aridai Resendiz Aguilar, MD

Paolo Pietro Bianchi, MD

Gianandrea Baldazzi., MD

Diletta CassiniI., MD

Stefano Berti, MD

Andrea Gennai, MD

Giuseppe Spingolo, MD

Dario Ribero, MD

Andrea Muratore, MD

Elio Jovine, MD

Raffaele Lombardi, MD

Gabriele Anania., MD

Stefano Scabini, MD

Giuseppe Navarra, MD

Romario Uberto Fumagalli, MD

Laura Adamoli, MD

Francesco Corcione, MD

Umberto Bracale, MD

Giuseppe Sica, MD

Domenico D'Ugo, MD

Alberto Biondi, MD

Aridai Resendiz, MD

Maurizio Degiuli, Professor

An Italian randomized controlled trial parallel-group in patients with a malignant tumor of the right or proximal transverse colon requiring right hemicolectomy.

This study aims to compare the Complete Mesocolic Excision With Central Vascular Ligation (CME+CVL) with the standard (non-CME) right hemicolectomy in patients with right or proximal transverse colon cancer stage II-IV(AJCC 8th edition) to determine the short and long term outcomes in terms of disease-free survival (DFS) as a primary endpoint, and safety, oncologic outcomes, quality of surgery and quality of life (QoL) as secondary endpoints.

Eligible patients will be randomized with a 1:1 ratio between CME + CVL vs standard non-CME right colectomy. The randomization sequence will be generated centrally by a computed algorithm and kept concealed to investigators.

The Right colectomy with CME + CVL includes the removal of the accessory lymphovascular supply at their origins by resecting the colon and mesocolon in an intact envelope of visceral peritoneum and mesenteric fascia. Despite the surgical approach and the type of procedure adopted, the operation should be strictly conducted following the general rules for colorectal oncologic resection, particularly as concerns proximal and distal margins length and lymph node retrieval.

All surgical approaches (open, laparoscopic, or robotic) will be allowed while the type of anastomosis performed and drain placement will be up to the surgeon's discretion.

Demographic, baseline, perioperative and postoperative characteristics will be analyzed as well.

The study expected to last six and a half years, of which one and a half years for recruiting 416 patients, 208 each arm, with five years of follow-up. Patients will be followed up at 1, 4, 12, 24, 36, and 60 months postoperatively.

Complete Mesocolic Excision in Comparison With Conventional Surgery for the Right Colon Cancer

Complete Mesocolic Excision With Central Vascular Ligation in Comparison With Conventional Surgery for the Right Colon Cancer: An Italian Randomized Trial

The length of time after surgery without any signs or symptoms of local or distant recurrence.

Total time from incision to skin closure expressed in minutes.

Defined by the volume drained in cm2 into aspiration systems and weight of gauzes, calculated, subtracting the weight of the dry gauzes and volume of saline solution used for irrigation.

Defined as the number of red blood cells, platelets, or plasma units transfused during the intraoperative time.

Defined as any deviation from the ideal intraoperative course occurring during the operative time, Using the Classiﬁcation of Intraoperative Complications(CLASSIC).

Number of patients with any deviation from the normal postoperative course grading by The Clavien-Dindo classification.

The number of patients with any deviation from the normal postoperative course grading by The Clavien-Dindo classification.

Defined as the length of an inpatient episode of care, calculated from the day of operation to the first discharge and based on the number of nights spent in the hospital.

The all-cause death rate, within 30 days after surgery in or out of the hospital.

Defined as the time from random assignment to the date of death due to any cause.

Defined as the length of time after Surgical treatment (CME+CVL or Conventional non-CME procedure) that the patient survives without any signs or symptoms of colon cancer.

The number of positive, negative, and total lymph nodes harvested, Quality of surgery specimen, quality of life by EORTC specific Questionnaires

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Right Colectomy for Colon Cancer Database (RCC). Surgical Technique, Route of Access and Quality of the Specimen	NCT06329102	Right Sided Col... Right Colectomy Lymphadenectomy	Surgical access	18 Years - 99 Years	Haukeland University Hospital
Open D3 Right Hemicolectomy Compared to Laparoscopic CME for Right Sided Colon Cancer	NCT03776591	Complication Quality of Life Surgical Proced... Lymph Node Meta... Circulating Tum...	Open surgery Right colectomy Laparoscopic su... Central lymphad...	18 Years - 85 Years	Haraldsplass Deaconess Hospital
Comparison of Intracorporeal and Extracorporeal Anastomoses for Minimally Invasive Right Colectomy	NCT03019016	Colonic Neoplas... Crohn Disease	Right Colectomy	18 Years -	Intuitive Surgical
Complete Mesocolic Excision in Comparison With Conventional Surgery for the Right Colon Cancer	NCT04871399	Colon Cancer	Conventional Ri... Right hemicolec...	18 Years - 85 Years	University of Turin, Italy
Comparison of Intracorporeal and Extracorporeal Anastomoses for Minimally Invasive Right Colectomy	NCT03019016	Colonic Neoplas... Crohn Disease	Right Colectomy	18 Years -	Intuitive Surgical

Spots Global Cancer Trial Database for right colectomy