Effect of comprehensive geriatric assessment for frail elderly patients operated for colorectal cancer-the colorectal cancer frailty study: study protocol for a randomized, controlled, multicentre trial.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer worldwide, with a median age of 72-75 years at diagnosis. Curative treatment usually involves surgery; if left untreated, symptoms may require emergency surgery. Therefore, most patients will be accepted for surgery, despite of high age or comorbidity. It is known that elderly patients suffer higher risks after surgery than younger patients, in terms of complications and mortality. Assessing frailty and offering frail elderly patients individualized treatment according to the comprehensive geriatric assessment (CGA) and care concept has been shown to improve the outcome for frail elderly patients in other clinical contexts. METHODS: This randomized controlled multicentre trial aims to investigate if CGA and care prior to curatively intended surgery for CRC in frail elderly patients will improve postoperative outcome. All patients ≥ 70 years with surgically curable CRC will be screened for frailty using the Clinical Frailty Scale (CFS-9). Frail patients will be offered inclusion. Randomization is stratified for colon or rectal cancer. Patients in the intervention group are, in addition to standard protocol, treated according to CGA and care. This consists of individualized assessments and interventions, established by a multiprofessional team. Patients in the control group are treated according to best known practice as stipulated by Swedish colorectal cancer treatment guidelines, within an enhanced recovery after surgery (ERAS) setting. The primary outcome is 90-day mortality. Secondary outcomes are the length of hospital stay and total number of hospital days within 3 months, discharge destination, 30-day readmission, ADL, safe medication assessment, CFS-9 score, complications, Health-Related Quality of Life (HRQoL) at 2-month follow-up in comparison to baseline measurements, health economical calculations including cost-effectiveness analysis based on costs of hospital care and primary care, mortality and HRQoL at baseline, 2- and 12-month follow-up and all-cause 1-year mortality. DISCUSSION: The trial is the first of its size and extent to investigate intervention with CGA and care prior to surgery for CRC in frail elderly patients. If this addition proves to be favourable, it could have implications on future care of frail elderly patients with CRC. TRIAL REGISTRATION: ClinicalTrials.gov NCT04358328. Registered on 4 February 2020.

Cost-effectiveness analysis of laparoscopic and open surgery in routine Swedish care for colorectal cancer.

BACKGROUND: Laparoscopic surgery for colorectal cancer has been shown in clinical trials to be effective regarding short-term outcomes and oncologically safe. Health economic analyses have been performed early in the learning curve when adoption of laparoscopic surgery was not extensive. This cost-effectiveness analysis evaluates laparoscopic versus open colorectal cancer surgery in Swedish routine care. METHODS: In this national retrospective cohort study, data were retrieved from the Swedish ColoRectal Cancer Registry. Clinical effectiveness, resource use and unit costs were derived from this and other sources with nationwide coverage. The study period was 2013 and 2014 with 1 year follow-up. Exclusion criterion comprised cT4-tumors. Clinical effectiveness was estimated in a composite endpoint of all-cause resource-consuming events in inpatient care, readmissions and deaths up to 90 days postoperatively. Up to 1 year, events predefined as related to the primary surgery were included. Costs included resource-consuming events, readmissions and sick leave and were estimated for both the society and healthcare. Multivariable regression analyses were used to adjust for differences in baseline characteristics between the groups. RESULTS: After exclusion of cT4 tumors, the cohort included 7707 patients who underwent colorectal cancer surgery: 6060 patients in the open surgery group and 1647 patients in the laparoscopic group. The mean adjusted difference in clinical effectiveness between laparoscopic and open colorectal cancer surgery was 0.23 events (95% CI 0.12 to 0.33). Mean adjusted differences in costs (open minus laparoscopic surgery) were $4504 (95% CI 2257 to 6799) and $4480 (95% CI 2739 to 6203) for the societal and the healthcare perspective respectively. In both categories, resource consuming events in inpatient care were the main driver of the results. CONCLUSION: In a national cohort, laparoscopic colorectal cancer surgery was associated with both superior outcomes for clinical effectiveness and cost versus open surgery.

Cost analysis in a randomized trial of early closure of a temporary ileostomy after rectal resection for cancer (EASY trial).

BACKGROUND: Hospital costs associated with the treatment of rectal cancer are considerable and the formation of a temporary stoma accounts for additional costs. Results from the EASY trial showed that early closure of a temporary ileostomy was associated with significantly fewer postoperative complications but no difference in health-related quality of life up to 12 months after rectal resection. The aim of the present study was to perform a cost analysis within the framework of the EASY trial. METHODS: Early closure (8-13 days) of a temporary stoma was compared to late closure (> 12 weeks) in the randomized controlled trial EASY (NCT01287637). The study period and follow-up was 12 months after rectal resection. Inclusion of participants was made after index surgery. Exclusion criteria were diabetes mellitus, steroid treatment, signs of postoperative complications or anastomotic leakage. Clinical effectiveness and resource use were derived from the trial and unit costs from Swedish sources. Costs were calculated for the year 2016 and analysed from the perspective of the healthcare sector. RESULTS: Fifty-five patients underwent early closure, and 57 late closure in eight Swedish and Danish hospitals between 2011 and 2014. The difference in mean cost per patient was 4060 US dollar (95% confidence interval 1121; 6999, p value < 0.01) in favour of early closure. A sensitivity analysis, taking protocol-driven examinations into account, resulted in an overall difference in mean cost per patient of $3608, in favour of early closure (95% confidence interval 668; 6549, p value 0.02). The predominant cost factors were reoperations, readmissions and endoscopic examinations. CONCLUSIONS: The significant cost reduction in this study, together with results of safety and efficacy from the randomized controlled trial, supports the routine use of early closure of a temporary ileostomy after rectal resection for cancer in selected patients without signs of anastomotic leakage. CLINICAL TRIAL: Registered at clinicaltrials.gov, clinical trials identifier NCT01287637.

Health Economic Analysis of Open and Robot-assisted Laparoscopic Surgery for Prostate Cancer Within the Prospective Multicentre LAPPRO Trial.

BACKGROUND: The rapid adoption of robot-assisted laparoscopy in radical prostatectomy has preceded data regarding associated costs. Qualitative evidence regarding cost outcomes is lacking. OBJECTIVE: This study assessed how costs were affected by robot-assisted laparoscopic prostatectomy (RALP) compared with open surgery. DESIGN, SETTING, AND PARTICIPANTS: Cost analysis was based on the dataset of the LAPPRO (Laparoscopic Prostatectomy Robot Open) clinical trial, which is a prospective controlled, nonrandomised trial of patients who underwent prostatectomy at 14 centres in Sweden between September 2008 and November 2011. Currently, data are available from a follow-up period of 24 mo. INTERVENTION: In the LAPPRO trial, RALP was compared with radical retropubic prostatectomy (RRP). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Costs per surgical technique were assessed based on resource variable data from the LAPPRO database. The calculation of average costs was based on mean values; Swedish currency was converted to purchasing power parity US dollar (PPP$). All tests were two-tailed and conducted at α=0.05 significance level. RESULTS AND LIMITATIONS: The cost analysis comprised 2638 men. Based on the LAPPRO trial data, RALP was associated with an increased cost/procedure of PPP$ 3837 (95% confidence interval: 2747-4928) compared with RRP. The result was sensitive to variations in caseload. Main drivers of overall cost were robotic system cost, operation time, length of stay, and sick leave. Limitations of the study include the uneven distribution between RALP and RRP regarding procedures in public/for-profit hospitals and surgeon/centre procedural volume. CONCLUSIONS: Based on the LAPPRO trial data, this study showed that RALP was associated with an increased cost compared with RRP in Swedish health care. There are many factors influencing the costs, making the absolute result dependent on the specific setting. However, by identifying the main cost drivers and/or most influential parameters, the study provides support for informed decisions and predictions. PATIENT SUMMARY: In this study, we looked at the cost outcome when performing prostatectomies by robot-assisted laparoscopic technique compared with open surgery in Sweden. We found that the robot-assisted procedure was associated with a higher mean cost.

The effect of pre- and post-operative physical activity on recovery after colorectal cancer surgery (PHYSSURG-C): study protocol for a randomised controlled trial.

BACKGROUND: Surgery for colorectal cancer is associated with a high risk of post-operative adverse events, re-operations and a prolonged post-operative recovery. Previously, the effect of prehabilitation (pre-operative physical activity) has been studied for different types of surgery, including colorectal surgery. However, the trials on colorectal surgery have been of limited methodological quality and size. The aim of this trial is to compare the effect of a combined pre- and post-operative intervention of moderate aerobic physical activity and inspiratory muscle training (IMT) with standard care on post-operative recovery after surgery for colorectal cancer. METHODS/DESIGN: We are conducting a randomised, controlled, parallel-group, open-label, multi-centre trial with physical recovery within 4 weeks after cancer surgery as the primary endpoint. Some 640 patients planned for surgery for colorectal cancer will be enrolled. The intervention consists of pre- and post-operative physical activity with increased daily aerobic activity of moderate intensity as well as IMT. In the control group, patients will be advised to continue their normal daily exercise routine. The primary outcome is patient-reported physical recovery 4 weeks post-operatively. Secondary outcomes are length of sick leave, complication rate and severity, length of hospital stay, re-admittances, re-operations, post-operative mental recovery, quality of life and mortality, as well as changes in insulin-like growth factor 1 and insulin-like growth factor-binding protein 3, perception of pain and a health economic analysis. DISCUSSION: An increase in moderate-intensity aerobic physical activity is a safe, cheap and feasible intervention that would be possible to implement in standard care for patients with colorectal cancer. If shown to be effective, this lifestyle intervention could be a clinical parallel to pre-operative smoke cessation that has already been implemented with good clinical results. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02299596 . Registered on 17 November 2014.

Health economic analysis of costs of laparoscopic and open surgery for rectal cancer within a randomized trial (COLOR II).

BACKGROUND: Previous studies regarding the comparative costs of laparoscopic and open surgery for rectal cancer provide ambiguous conclusions, and there are no large randomized trials or long-term follow-up. METHODS: A prospective cost-minimization analysis was carried out by using data of clinical resource use from the randomized controlled trial COLOR II. Some data needed for the health economic evaluation were not collected in the clinical trial; therefore, a retrospective data collection was made for COLOR II-patients operated at the largest participating Swedish hospital (n = 105). Sick leave information was provided by the Swedish social insurance agency. Unit costs were collected from Swedish sources. The primary outcome was the difference in mean cost between laparoscopic and open surgery. RESULTS: The COLOR II-trial enrolled 1044 rectal cancer patients randomized between laparoscopic and open surgery 2:1. At the 3-year follow-up data for the clinical variables used in the analysis were available for 74-89 % of patients. Laparoscopic surgery costs the health care sector more than the open technique, both at 28 days ($1910, 95 % CI 677-3143) and 3 years ($3854, 95 % CI 1527-6182) after surgery. There were, however, no differences in long-term costs to society between laparoscopic and open surgery ($684, 95 % CI -5799 to 7166). CONCLUSIONS: Though the study found short- and long-term cost differences for the healthcare sector, there was no difference in regard to the long-term societal perspective. Future research is suggested to investigate the effects of sick leave costs using material from a greater number of patients.

Stoma-Const--the technical aspects of stoma construction: study protocol for a randomised controlled trial.

BACKGROUND: The construction of a colostomy is a common procedure, but the evidence for the different parts of the construction of the colostomy is lacking. Parastomal hernia is a common complication of colostomy formation. The aim of this study is to standardise the colostomy formation and to compare three types of colostomy formation (one including a mesh) regarding the development of parastomal hernia. METHODS/DESIGN: Stoma-Const is a Scandinavian randomised trial comparing three types of colostomy formation. The primary endpoint is parastomal herniation as shown by clinical examination or CT scan within one year. Secondary endpoints are re-admission rate, postoperative complications (classified according to Clavien-Dindo), stoma-related complications (registered in the case record form at stoma care nurse follow-up), total length of hospital stay during 12 months, health-related quality of life and health economic analysis as well as re-operation rate and mortality within 30 days and 12 months of primary surgery. Follow-up is scheduled at 4-6 weeks, and 6 and 12 months. Inclusion is set at 240 patients. DISCUSSION: Parastomal hernia is a common complication after colostomy formation. Several studies have been performed with the aim to reduce the rate of this complication. However, none are fully conclusive and data on quality of life and health economy are lacking. The aim of this study is to develop new standardised techniques for colostomy formation and evaluate this with patient reported outcomes as well as clinical and radiological assessment. TRIAL REGISTRATION: Clinicaltrials.gov, NCT01694238.2012-09-24.

Treatment of acute diverticulitis laparoscopic lavage vs. resection (DILALA): study protocol for a randomised controlled trial.

BACKGROUND: Perforated diverticulitis is a condition associated with substantial morbidity. Recently published reports suggest that laparoscopic lavage has fewer complications and shorter hospital stay. So far no randomised study has published any results. METHODS: DILALA is a Scandinavian, randomised trial, comparing laparoscopic lavage (LL) to the traditional Hartmann's Procedure (HP). Primary endpoint is the number of re-operations within 12 months. Secondary endpoints consist of mortality, quality of life (QoL), re-admission, health economy assessment and permanent stoma. Patients are included when surgery is required. A laparoscopy is performed and if Hinchey grade III is diagnosed the patient is included and randomised 1:1, to either LL or HP. Patients undergoing LL receive > 3L of saline intraperitoneally, placement of pelvic drain and continued antibiotics. Follow-up is scheduled 6-12 weeks, 6 months and 12 months. A QoL-form is filled out on discharge, 6- and 12 months. Inclusion is set to 80 patients (40+40). DISCUSSION: HP is associated with a high rate of complication. Not only does the primary operation entail complications, but also subsequent surgery is associated with a high morbidity. Thus the combined risk of treatment for the patient is high. The aim of the DILALA trial is to evaluate if laparoscopic lavage is a safe, minimally invasive method for patients with perforated diverticulitis Hinchey grade III, resulting in fewer re-operations, decreased morbidity, mortality, costs and increased quality of life. TRIAL REGISTRATION: British registry (ISRCTN) for clinical trials ISRCTN82208287http://www.controlled-trials.com/ISRCTN82208287.