Abstract
Background/Aim: There are no studies assessing the long-term quality of life (QoL) following three-dimensional laparoscopy cholecystectomy (3D-LC) in patients with cholelithiasis (Chole). Patients and Methods: A cohort of 200 patients with Chole were randomized into 3D-LC or minilaparotomy cholecystectomy (MC) groups. RAND-36 survey was performed before randomization, four weeks and five years postoperatively. Results: Similar postoperative five years RAND-36 scores were reported in the 3D-LC and MC groups. The MC and 3D-LC groups combined analysis, social functioning (SF, p=0.007), mental health (MH, p=0.001), role physical (RP, p<0.001) and bodily pain (BP, p<0.001) domains increased significantly. In comparison to the Finnish reference RAND-36 (FRR) scores, the scores at five years increased significantly in the MH domain, while four RAND-36 domains; Physical functioning (PF), general health (GH), RP, BP remained significantly lower in comparison to the FRR scores. Conclusion: A relatively similar long-term outcome in the 3D-LC and MC patients is shown. Interestingly, five RAND-36 domains increased during five years follow-up, while four RAND-36 domains remained lower than FRR scores, which may indicate onset of possible new symptoms following cholecystectomy in long-term follow-up.
Cholelithiasis (Chole) and cholecystitis are among the most common diseases needing operative management worldwide with almost 18 million cholecystectomies (Ccy) performed every year (1, 2). Most quality of life (QoL) reports following Ccy assess short-term outcomes including perioperative course, early complications, duration of hospital stay, morbidity and mortality, while, very few studies on long-term (QoL) are available, although many Ccy patients report continuous symptoms or appearance of new abdominal symptoms following Ccy (3-6). Therefore, long-term QoL of Ccy patients with the patient-reported outcome measures (PROMs) are important tools for assessing QoL from a patient’s own experience. A lack of long-term evaluation with PROMs is also internationally recognized (3-9) and many national healthcare organizations such as National Institute for Health and Care Excellence (NICE) suggest feedback (10) from patients to enhance QoL and assess various treatment procedures. In addition, earlier studies of PROMs following Ccy strongly focus on surgical outcomes and little on the assessment of the Ccy patient’s own experience (3-9). NICE recommends wider use of PROMs to report important outcomes, including the recurrence of symptoms and appearance of new symptoms that affect long-term QoL in patients undergoing Ccy (10).
Recently, Saimanen et al. (11) assessed the 3-year QoL of Ccy patients using the RAND-36-Item Health Survey. A cohort of 110 Chole patients were randomized to minilaparotomy cholecystectomy (MC) or standard 2-dimensional (2D) laparoscopic cholecystectomy (2D-LC). The RAND-36 survey was performed before randomization, four weeks, six months, and three years postoperatively. During follow-up, four RAND-36 domains remained significantly higher, indicating a significant positive change in QoL. Authors concluded that the RAND-36 survey is a comprehensive test for analyzing long-term QoL after Ccy.
In further analyses (12), the same authors investigated the 8-year QoL after MC versus 2D-LC for Chole by using the RAND-36 in a cohort of 88 patients with Chole randomized to undergo either MC or 2D-LC. In three RAND-36 domains, the MC procedure had significantly better scores than the age- and sex-adjusted Finnish reference RAND-36 (FRR) scores (13). Unfortunately, there is a lack of preoperative RAND-36 survey of Ccy patients in this report (12).
Most recently, the same authors assessed 200 patients with Chole randomized into three-dimensional laparoscopy cholecystectomy (3D-LC) or MC groups (14). RAND-36 survey was performed before randomization and four weeks post-surgery, while no significant differences in study domains were shown. Authors concluded that a longer follow-up after Ccy is needed for final conclusions to be drawn. To our knowledge, the long-term QoL of 3D-LC patients has not been assessed earlier by RAND-36 survey. Therefore, our study aim was to assess RAND-36 items four weeks and five years following surgery in Ccy patients.
Patients and Methods
The study was approved by the Ethics Committee of Kuopio University Hospital District, Kuopio, Finland (DNRO 27/02/2013), it was registered in the ClinicalTrials.gov database (ClinicalTrials.gov Identifier: NCT01723540) and was conducted in accordance with the Declaration of Helsinki. The study included 200 patients with Chole divided in 3D-LC (n=112) or MC (n=88) groups (Table I). The surgical techniques used are detailed in previous reports by Eskelinen et al. (14, 15).
Baseline data for the minicholecystectomy (MC) and three-dimensional laparoscopy cholecystectomy (3D-LC) groups. Data are mean (standard deviation), median (range) or number of cases.
RAND-36 was assessed before randomization and four weeks and five years post-surgery using the validated FRR questionnaire (13). The eight domains were calculated from the 36 questions as instructed by the RAND-36 survey; Physical functioning (PF), Social functioning (SF), vitality (VT), mental health (MH), role physical (RP), role emotional (RE), bodily pain (BP), general health (GH). The instructions for calculation of the eight domains from the 36 questions of the RAND-36 survey are detailed in previous reports by Harju et al. (16) and Aspinen et al. (17).
The group comparisons were executed by independent samples t-test and chi-square test or Fisher’s exact test. RAND-36 domains were expressed as means and standard deviations. Linear mixed effect model (LME) was used to test group differences at time points and overall effect group x time in Table II. Table III presents differences between time points using LME model. RAND-36 domain score values were tested by one-sample t-test against FRR score values separately for four weeks and five years follow-up. Data were analyzed using IBM SPSS statistical software (IBM SPSS Statistics for Windows, version 26.0, IBM Corporation Armonk, NY, USA).
The RAND-36 scores between minilaparotomy cholecystectomy (MC) and 3D laparoscopic cholecystectomy (LC) groups.
The RAND-36 scores preoperative, 4 weeks after surgery, 5 years after surgery for the minilaparotomy cholecystectomy (MC) and 3D laparoscopic cholecystectomy (LC) groups combined.
Results
Preoperatively, 84 patients (84/88=95.4%) in the MC group and 106 (106/112=94.6 %) patients in the 3D-LC group were reached for the RAND-36 procedure. Further on, 66 (66/84=78.6 %) of the MC patients and 82 (82/106=77.4%) of the 3D-LC patients returned the four weeks, while 67 (67/84=79.8%) of the MC patients and 84 (84/106=79.2%) of the 3D-LC patients returned the 5 years RAND-36 questionnaire (Figure 1, Table I).
The flowchart of the study design.
No significant differences were found in any of the eight domains of RAND-36 preoperatively or at 4 weeks and 5 years following surgery between the MC and 3D-LC groups (Table II). In the MC and 3D-LC groups combined analysis (Table III), the RAND-36 scores increased significantly in the SF (mean preoperative score 78.0 vs. 5 years postoperative score 83.8, LME analysis p-value=0.007), MH (mean preoperative score 76.4 vs. 5 years postoperative score 78.0, LME analysis p-value=0.001), RP (mean preoperative score 64.4 vs. 5 years postoperative score 72.8, LME analysis p-value<0.001), and BP (mean preoperative score 54.8 vs. 5 years postoperative score 70.7, LME analysis p-value<0.001), while the GH (mean preoperative score 63.3 vs. 5 years postoperative score 62.2, LME analysis p- value=0.004) remained significantly lower indicating the decreased general health during five years (Table III).
The 4-week and 5 years postoperative scores of eight RAND-36 domains in MC and 3D-LC groups combined versus the FRR scores are shown in Figure 2. In comparison to the FRR scores, the RAND-36 scores at four weeks and five years increased significantly in the MH domain (p<0.001 and p<0.001, respectively), while four RAND-36 domains; PF (p<0.001 and p<0.001, respectively), GH (p=ns and p<0.004, respectively), RP (p<0.001 and p=ns, respectively), BP (p<0.001 and p<0.001, respectively) remained significantly lower in comparison to the FRR scores.
The mean (95% confidence interval) scores of the RAND-36 domains between two time points; 4 weeks and 5 years postoperatively for the cholecystectomy patients (minilaparotomy cholecystectomy and 3D-laparoscopic cholecystectomy groups combined) compared to age- and sex-adjusted Finnish reference scores (dashed line).
Discussion
Earlier QoL reports following Ccy relate outcome to early complications, duration of hospitalization, morbidity, and mortality, often lack of assessment on the patients’ own experience (3-9). There is a consensus that previous features could be poor measures of QoL for elective surgery such as Ccy, where perioperative harms are infrequent (18, 19), while the main aim is to minimize morbidity, and improve QoL. These features are not captured using these tools: they can only be captured by asking patients’ own experience (20, 21). PROMs shows QoL data that come directly from the patient, and several PROMs have been developed for clinical use (22, 23). A recent review found that 27% of registered clinical trials used at least one PROM (23). Each PROM contains a tool with different questions, grouped into domains capturing QoL features. Unfortunately, previous reports have shown significant heterogeneity in the assessment of PROMs postoperatively (24, 25), which may limit the usage of PROMs as research tool and hinder the comparison of different QoL studies.
There is particular interest in the use of PROMs to assess elective surgical techniques such as Ccy. Ccy is one of the most widely used gastro-surgical operation with 750,000 operations executed annually in the United States (26) and almost 18 million Ccys worldwide every year (1, 2). Low rates of morbidity and mortality mean that classical tools may not accurately intercept the QoL of Ccy patients following surgery. PROMs are important following surgery, because Ccy is often executed to enhance QoL and it would be futile if patients undergoing Ccy did not report their own experiences with the procedure.
The PROM tools, SF-36 and RAND-36 are validated, free to use, QoL devices and have the advantage of being assessed in different diseases (27-33). Nishikawa et al. (27) investigated longitudinal quality of life (QOL) change assessed retrospectively using the SF-36 in a cohort 184 patients with chronic liver diseases (CLDs). However, the change in SF-36 domains did not reach statistical significance in multivariate analysis. Fritsch et al. (28) assessed QoL of patients with systemic lupus erythematosus (SLE) after balneotherapy in their randomized, controlled, follow-up study. In addition to the standard of care (SOC), 16/30 (53%) patients with SLE received balneotherapy (3-week period, 15 times, for 30 min) and 14/30 (47%) patients received the SOC only. Several SF-36 domains of physical condition improved significantly after therapy and the improvement remained statistically significant (p=0.019). Especially, GH improved significantly by the end of the course (p=0.001). Pozsgai et al. (29) found a possible new application for PROMs by identifying and summarizing manual therapy (MT) related clinical trials to recognize the importance of MT in clinical practice. Authors assessed the interventions and outcomes in MT related clinical trials in the review report (29). Costanzo et al. (30) used PROMs investigated the relationship between the Mediterranean diet, cardiovascular risk and meningiomas, while Kinoshita et al. (31) reported postoperative limb function and QoL in elderly patients with bone tumours and soft tissue sarcoma by using PROM tool.
In spite of the recent reports, there is a lack of reports regarding patients undergoing Ccy showing their own experiences with the procedure. RAND-36 and SF-36 contain the same set of domains; however, the scoring differed slightly in the domains of GH and BP (27-33). Instead, SF-12 is a shortened version of the SF-36 (6, 34) and it reduces the time for filling the questionnaire. Unfortunately, SF-12 lacks some specific questions needed in Chole. Authors chose RAND-36, because it was reported earlier for reliability and reference values in the Finnish general population (13). The authors reason for their choice of PROM method in each study was reported in a review by Melly et al. (6), where 4/21 (19%) of investigators chose a tool validated in their own language, 33% (7/21) selected a tool validated previously, and 3/21 researchers chose a tool validated in Ccy patients (6). Unfortunately, only 2/6 (33%) SF-36 studies chose preoperative questionnaire (6).
Saimanen et al. (11) assessed the 3-year health status of 110 Ccy patients randomized to MC or 2D-LC groups. The RAND-36 survey was completed before randomization, four weeks, six months, and three years post-surgery. RAND-36 scores improved in several domains in MC and 2D-LC groups with a similar postoperative course over the 3-year study period. In addition, at the 3-year follow-up telephone interview, no significant differences in PROMs between MC and 2D-LC patients were shown. In the LME model, VT, MH (0.03), RP and BP domains showed statistically significant differences.
In further analyses (12), the same authors investigated QoL in a cohort of 88 patients with Chole randomized to either MC (n=44) or 2D-LC (n=44). The RAND-36 survey was completed eight years postoperatively. In three RAND-36 domains (SF, RP, RE), the MC procedure was significantly better than 2D-LC. In MC patients, the 8-year postoperative scores of SF (p<0.001), RP (p=0.002) and RE (p<0.001) were significantly higher than the FRR scores. The authors concluded that the RAND-36 survey can be used as a valid and reliable method for measuring the QoL of Ccy patients.
Most recently, the same authors investigated a cohort of 200 patients with Ccy randomized into 3D-LC or MC groups. RAND-36 was completed before randomization and four weeks post-surgery (14). There were no significant differences in RAND-36 domains between study groups. When the patients in both study groups were combined, and preoperative scores were compared to four weeks scores, the four weeks scores of MH, BP, and GH domains were significantly higher than the preoperative scores of these domains. In comparison to the FRR scores, scores at four weeks were significantly higher for the MH domain, whilst scores were significantly lower in four other domains: PF, SF, BP, and RP. Authors concluded that a longer follow-up after Ccy is needed for final conclusions regarding QoL to be drawn (14).
In the present study, three of four Ccy patients (151/190, 79%) were reached for RAND-36 survey five years post-surgery and it was possible to show valid and reliable results for QoL assessment in long-term follow-up. Interestingly, this investigation differs from the results of the electronic RAND-36 (eRAND-36) survey by Dalia et al. (35) in Chole patients following the 2D-LC procedure, where 61/200 (30%, at 4 weeks), 54/200 (27%, at 12 weeks) and 38/200 (19%, at 24 weeks) of the patients were reached for the RAND-36 survey and therefore long-term QoL assessment of 2D-LC patients was difficult, which may limit the utility eRAND-36 as clinical research tool in the assessment of QoL in LC patients.
The strengths of the study are; i) a study cohort of 200 patients, ii) cohort comparable to the FRR validation cohort (13), iii) high rate of participation both preoperative, four weeks and five years postoperative RAND-36 survey and iv) the MC and 3D-LC combined analysis, where four RAND-36 domains (SF, MH, RP, and BP) increased significantly following surgery indicating a positive change in QoL five years postsurgery.
Conclusion
PROMs are rarely assessed in 3D-LC patients. Melly et al. (6) reviewed 4960 articles of which only 21 articles met all criteria of their PROM final review. There were only two (9.5%) randomized clinical trials and only two studies used preoperative SF-36 questionnaire (6). The present study shows similar long-term QoL scores in 3D-LC and MC patients. Interestingly, five RAND-36 domains increased significantly in 5 years follow-up, while four RAND-36 domains remained lower than FRR scores, which may indicate onset of possible new symptoms following Ccy in long-term follow-up.
Acknowledgements
The study was funded by the North Savo Regional Fund (Pohjois-Savon Maakuntarahasto).
Footnotes
Authors’ Contributions
All Authors contributed to the collection and analysis of data, drafting, and revising the manuscript, read and approved the final article.
Conflicts of Interest
The Authors have no conflicts of interest or financial ties to disclose in relation to this study.
- Received December 20, 2023.
- Revision received January 22, 2024.
- Accepted January 23, 2024.
- Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved
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