Colorectal Neoplasms, Secondary Malignant Neoplasm of Liver
Conditions
Keywords
Open liver resection, Laparoscopic liver resection, Colorectal cancer liver metastases
Brief summary
The purpose of the study is to compare outcomes of laparoscopic versus open liver resection for colorectal metastases in a prospective and randomized study. The study will include all non-anatomic liver resections in our institution. The primary end point is that the use of laparoscopic technique significantly can reduce the frequency of complications to liver resection. Secondary end points are 5-year survival, immediate surgical outcomes, quality of life and degree of impairment of the immune system.
Detailed description
Full protocol is published open access in Trialsjournal: http://www.trialsjournal.com/content/16/1/73
Interventions
PROCEDUREOpen liver resection
Patients will be operated with open liver resection for colorectal metastasis
PROCEDURELaparoscopic liver resection
Patients will be operated with laparoscopic liver resection
Sponsors
Helse Sor-Ost
Oslo University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients eligible for radical liver resection without formal liver resection or without assistance of radiofrequency ablation
Exclusion criteria
* Inability to give written informed concent * Patients with tumors that can't be resected without reconstruction of vessels or bile ducts * Patients with tumors that can't be resected without 1)formal liver resection 2)combination with radiofrequency ablation * Patients with extrahepatic metastasis except resectable metastasis in lungs and adrenals * Pre- and peroperative diagnosis of non radically treatable disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 30 Days Perioperative Morbidity | Within 30 days after surgery | This study aims to compare major intraoperative and postoperative parameters in patients randomized to either laparoscopic or open liver resection. Pre- and perioperative events relevant for surgical outcomes will be registered. The following intraoperative parameters will be compared: operative time, blood loss, blood transfusion, while intraoperative incidents will be classified according to the Satava classification. Morbidity within the first 30 days is the primary outcome (morbidity, yes/no), and will be classified and analysed according to the validated classification for postoperative morbidity as described by Dindo et al, by the Accordion system and by the Comprehensive Complication Index |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Recurrence Pattern | 5 years | Pattern of recurrence in liver and extrahepatic. Studied by postoperative CT every 4 months for 2 years and every 6 months for the following 3 years. Local recurrence and new tumors will be recorded. |
| Immediate Oncologic Outcome | 2 months after surgery | Immediate oncologic outcome is the result of surgical specimen evaluation - evaluation of tumor resection margins. |
| Postoperative Quality of Life | Up to 2 years | Evaluation of postoperative quality of life at baseline, 1 month, 4 months and 2 years using the SF-36 and the EORTC qlq-30 lmc-21 forms |
| Surgical Trauma and Activation of the Immune System | 72 hours | Evaluation of surgical trauma caused by open and laparoscopic resection by means of analyzing complement and cytokine activation at set perioperative time points. |
| Health Economy | 1 year | We intend to compare overall cost of treatment for the hospital and for the health care system |
| Severity of Postoperative Pain | 4 months | To compare pain the first 5 postoperative days, at 1 month and 4 months. Patients in the open group will be randomized to receiving either a patient controlled analgesic pump containing opioids, or a patient controlled epidural analgesic pump. In laparoscopic group all patients will receive a PCA. |
| Molecular Biology | 20 years | The aim is to perform molecular characterization of biological samples harvested perioperatively and during follow-up, and to correlate results with clinical end points. |
| 5 Year Survival | 5 years after surgery | 5 year survival * overall * disease free * recurrence free |
| Imaging | 5 years | The aim is to evaluate two new imaging methods, CT perfusion of liver and LIME-PET, in order to optimize the preoperative identification of colorectal liver metastases. |
| Severity of Morbidity | 30 days | Severity of complications will be assessed by the Comprehensive Complication Index and the Accordion system |
| Level of Adhesions | 2 years | Level of adhesions will be recorded during repeated liver resection in patients formerly randomized to open or laparoscopic liver resection. a modified version of the peritoneal adhesion index will be used for scoring. |
| Number of Patients That Complete Adjuvant Oncologic Treatment | 1 year | Time from operation to initiation of oncologic treatment, and the total number of courses given will be recorded and compared between the groups. |
| Readmissions | 30 days | Readmissions within 30 days after surgery will be recorded, both admissions to Oslo University Hospital and to referring hospitals. |
| Incidence of Incisional Hernia | 1 year | CT scans will be performed to examine for incisional hernia 1 year after surgery |
| Anti-tumor Immunology | 20 years | The aim is to evaluate immunological parameters related to anti-tumor immunity and inflammatory factors |
Countries
Norway
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Open Liver Resection Patients will be operated with open liver resection
Open liver resection: Patients will be operated with open liver resection for colorectal metastasis | 147 |
| Laparoscopic Liver Resection Patients will be operated with laparoscopic liver resection
Laparoscopic liver resection: Patients will be operated with laparoscopic liver resection | 133 |
| Total | 280 |
Baseline characteristics
| Characteristic | Open Liver Resection | Laparoscopic Liver Resection | Total |
|---|---|---|---|
| Age, Continuous | 66 years STANDARD_DEVIATION 10 | 67 years STANDARD_DEVIATION 8 | 66 years STANDARD_DEVIATION 9 |
| Region of Enrollment Norway | 147 Participants | 133 Participants | 280 Participants |
| Sex: Female, Male Female | 60 Participants | 56 Participants | 116 Participants |
| Sex: Female, Male Male | 87 Participants | 77 Participants | 164 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 147 | 0 / 133 |
| other Total, other adverse events | 0 / 147 | 0 / 133 |
| serious Total, serious adverse events | 10 / 147 | 4 / 133 |
Outcome results
Primary
30 Days Perioperative Morbidity
This study aims to compare major intraoperative and postoperative parameters in patients randomized to either laparoscopic or open liver resection. Pre- and perioperative events relevant for surgical outcomes will be registered. The following intraoperative parameters will be compared: operative time, blood loss, blood transfusion, while intraoperative incidents will be classified according to the Satava classification. Morbidity within the first 30 days is the primary outcome (morbidity, yes/no), and will be classified and analysed according to the validated classification for postoperative morbidity as described by Dindo et al, by the Accordion system and by the Comprehensive Complication Index
Time frame: Within 30 days after surgery
Population: Modified intention to treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open Liver Resection | 30 Days Perioperative Morbidity | 44 Complications Accordion grade 2 or highe |
| Laparoscopic Liver Resection | 30 Days Perioperative Morbidity | 24 Complications Accordion grade 2 or highe |
Secondary
5 Year Survival
5 year survival * overall * disease free * recurrence free
Time frame: 5 years after surgery
Secondary
Anti-tumor Immunology
The aim is to evaluate immunological parameters related to anti-tumor immunity and inflammatory factors
Time frame: 20 years
Secondary
Health Economy
We intend to compare overall cost of treatment for the hospital and for the health care system
Time frame: 1 year
Secondary
Imaging
The aim is to evaluate two new imaging methods, CT perfusion of liver and LIME-PET, in order to optimize the preoperative identification of colorectal liver metastases.
Time frame: 5 years
Secondary
Immediate Oncologic Outcome
Immediate oncologic outcome is the result of surgical specimen evaluation - evaluation of tumor resection margins.
Time frame: 2 months after surgery
Secondary
Incidence of Incisional Hernia
CT scans will be performed to examine for incisional hernia 1 year after surgery
Time frame: 1 year
Secondary
Level of Adhesions
Level of adhesions will be recorded during repeated liver resection in patients formerly randomized to open or laparoscopic liver resection. a modified version of the peritoneal adhesion index will be used for scoring.
Time frame: 2 years
Secondary
Molecular Biology
The aim is to perform molecular characterization of biological samples harvested perioperatively and during follow-up, and to correlate results with clinical end points.
Time frame: 20 years
Secondary
Number of Patients That Complete Adjuvant Oncologic Treatment
Time from operation to initiation of oncologic treatment, and the total number of courses given will be recorded and compared between the groups.
Time frame: 1 year
Secondary
Postoperative Quality of Life
Evaluation of postoperative quality of life at baseline, 1 month, 4 months and 2 years using the SF-36 and the EORTC qlq-30 lmc-21 forms
Time frame: Up to 2 years
Secondary
Readmissions
Readmissions within 30 days after surgery will be recorded, both admissions to Oslo University Hospital and to referring hospitals.
Time frame: 30 days
Secondary
Recurrence Pattern
Pattern of recurrence in liver and extrahepatic. Studied by postoperative CT every 4 months for 2 years and every 6 months for the following 3 years. Local recurrence and new tumors will be recorded.
Time frame: 5 years
Secondary
Severity of Morbidity
Severity of complications will be assessed by the Comprehensive Complication Index and the Accordion system
Time frame: 30 days
Secondary
Severity of Postoperative Pain
To compare pain the first 5 postoperative days, at 1 month and 4 months. Patients in the open group will be randomized to receiving either a patient controlled analgesic pump containing opioids, or a patient controlled epidural analgesic pump. In laparoscopic group all patients will receive a PCA.
Time frame: 4 months
Secondary
Surgical Trauma and Activation of the Immune System
Evaluation of surgical trauma caused by open and laparoscopic resection by means of analyzing complement and cytokine activation at set perioperative time points.
Time frame: 72 hours