1 2 3 4 5 6 7 3 8 8 9 11 12 14 15 16 17 18 20 21 Objective 21 Methods All patients with symptomatic cholecystolithiasis visiting the outpatients clinic of the St. Elisabeth hospital in Tilburg were considered for inclusion in a blind randomised trial comparing laparoscopic and small-incision cholecystectomy. Verbal and written informed consent was obtained from each patient, and patients were consecutively listed for elective cholecystectomy. Health status was a secondary outcome measure as part of the randomised clinical trial. Sample size 8 18 Randomisation 22 A random-number table was used for the generation of the allocation sequence and allocation concealment was guaranteed by using sealed envelopes. To eliminate bias caused by preoperative expectations, patients were randomised in the operation theatre after induction of anaesthesia. A telephone call to the secretary office was made and an employee opened an envelope. All patient data were recorded in a case record form, with the procedure reported as ‘trial cholecystectomy’. Wounds and port sites were dressed with identical opaque dressings, stained using iodine, regardless of the surgical procedure performed, to allow blinding for patient, nurses, and physicians during the postoperative period. The type of operation was revealed just before discharge. No patients were lost to follow-up. Operative procedures were standardised apart from using a laparoscopic or small-incision technique. Anaesthesia, postoperative care and analgesic use were also standardised. Inclusion and exclusion criteria 23 Exclusion criteria were: age younger than 18 years, choledocholithiasis (icterus, acholic faeces and/or bilirubine twice normal range), cholangitis, known pregnancy, moderate to severe systemic disease (ASA III and higher), known cirrhosis of the liver, history of abdominal malignancy, previous upper abdominal surgery (precluding laparoscopic approach), psychiatric disease, or another reason (e.g. lack of knowledge of the Dutch language) for making follow-up or completion of questionnaires unreliable. 24 Surgical procedures 24 Laparoscopic cholecystectomy 25 ® Small-incision cholecystectomy 24 26 32 ® Postoperative protocol Early oral intake and mobilization were encouraged. Patients left the hospital as soon as they felt capable. As patients were admitted at the day of operation, hospital stay was defined as the number of nights (postoperative) in hospital. Shortly before discharge, wound dressings were removed for wound inspection. For logistic reasons, we were not able to blind the surgeon at the patients’ follow-up. Follow-up took place according to a standardised scheme after 2 weeks, 6 weeks, and 3 months. Patients were encouraged to resume work and normal daily activity as soon as they felt capable to do so. Measurements 21 33 34 34 35 36 36 37 33 33 Statistical analysis ® Repeated measures analysis of variance (ANOVA) was used to evaluate health status differences over time between the two operative techniques. t t Results 1 Fig. 1 Revised consort statement diagram showing the flow of participants through each stage of the randomised trial [38]  Baseline characteristics and operative results 1 2 Table 1 Patient characteristics  n n P Male 31 (25.8%) 30 (21.9%) 0.459 Female 89 (74.2%) 107 (78.1%)  Age (years)   Mean (SD) 48.4 (14.1) 48.5 (14.0) 0.974   Median (range) 49 (17–77) 48 (18–80)  BMI   Mean (SD) 27.5 (4.8) 27.9 (4.6) 0.500   Median (range) 26.8 (18.5–45.9) 27,2 (18.0–43.3)  ASA stage   I 81 (67.5%) 91 (66.4%) 0.855   II 39 (32.5%) 46 (33.6%)  BMI ASA Table 2 Operative features and difficulties of laparoscopic and small-incision cholecystectomy  n n P Patients with complicated gallstone diseases before cholecystectomy 18 18 0.668 Endoscopic retrograde cholangiopancreaticography 12 13 0.890 Duration of symptoms (weeks) n n 0.443   mean (SD) 61.1 (108.8) 70.3 (147.2)   median (range) 26 (2–884) 17.5 (1–1040) # n n 0.196   mean (SD) 76.1 (33.8) 76.0 (24.0)   median (range) 65 (40–200) 66 (49–165) Inflammation 21 25 0.876 Operative team:   surgeon–resident 15 (12.5%) 21 (15.3%) 0.515   resident–surgeon 84 (70.0%) 100 (73.0%) 0.596   resident–resident 21 (17.5%) 18 (13.1%) 0.331 Hospital stay *   mean (SD) 2.4 (4.6) 3.1 (12.4) 0.560   median (range) 1 (1–36) 2 (1–144) Hospital stay * (without one extreme value)   mean (SD) 2.1 (3.38) 2.04 (2.42) 0.877 n 50 51 Return to work (weeks)   mean (SD) 4.1 (2.3) 3.7 (2.0) 0.298   median (range) 4 (1–12) 3 (0.5–12) # * hospital stay in postoperative nights 3 Table 3 Serious complications in laparoscopic and small-incision cholecystectomy (intraoperative and postoperative) Laparoscopic cholecystectomy 11 Small-incision cholecystectomy 7 Intraoperative complications Asystole  1 Cardiac ischemia, no elevated enzymes  1 Common bile duct (CBD) injury, eventually hepatico-jejunostomy, complicated prolonged ICU stay, stenosis bile duct. 1 CBD injury, conversion, T-drain, ERCP and papillotomy for CBD stone 1 Bleeding requiring conversion (and transfusion) 1 Hepatic parenchyma rupture, conservative treatment (transfusion)  1 Bowel injury at introduction (sutured) 1   Cerebrovascular accident at recovery 1   Total intraoperative 5 Total intraoperative 3 Postoperative complications Pneumonia 1 Cystic duct leakage (ERCP + stent) 1 Cerebrovascular accident (6 weeks postoperative) 1 CBD injury, multiple relaparotomies and ICU stay  1 Intra-abdominal fluid collection (haematoma); icterus (ERCP: no stones, complicated by bleeding) 1 CBD stone (ERCP) and abscess intra-abdominal (ultrasound drainage) 1 Pancreatitis (conservative treatment)  1 CBD stone with pancreatitis (ERCP) 1 Intra-abdominal abscess (re-laparoscopy) 1   Epididimitis (operation by urologist) 1   Total postoperative 6 Total postoperative 4 CBD ICU ERCP U p p There were no differences in the preoperative measurements of the SF-36 subscales, all the GIQLI subscales, the total GIQLI score and the BIQ subscales. Health status The questionnaires were obtained with a response rate varying from 87.5% preoperatively to 77.4% three months postoperatively. The nonresponders did not differ from those who remained in the study with regard to complications (16%), operative time (65 minutes), hospital stay (1.5 days), return to work (3.2 weeks) or baseline scores. F df p 4 p p Table 4 Comparison of GIQLI, SF-36 and BIQ scores in laparoscopic (LC) and small-incision cholecystectomy (SIC) according to intention-to-treat (mean scores and SD)   Preoperative Postoperative P day 1 2 weeks 6 weeks 12 weeks SF-36 Physical LC 77.0 (23.0) 57.1 (29.5) 67.5 (23.2) 83.2 (21.2) 87.8 (17.4) 0.413 SIC 83.0 (18.3) 39.9 (29.8) 63.0 (22.8) 83.1 (20.8) 87.5 (19.3) Social LC 43.4 (14.2) 77.8 (19.9) 70.7 (23.9) 86.5 (19.3) 91.9 (15.9) 0.260 SIC 42.7 (17.1) 74.3 (22.6) 66.3 (25.8) 82.3 (22.9) 90.4 (19.0) Role physical LC 56.4 (43.4) 52.6 (43.2) 26.7 (36.4) 67.4 (40.1) 81.1 (34.9) 0.667 SIC 60.8 (44.4) 53.0 (45.7) 29.5 (49.4) 54.8 (42.6) 79.2 (35.8) Role emotion LC 73.7 (39.4) 70.5 (38.8) 68.3 (41.7) 82.7 (33.6) 88.6 (27.8) 0.797 SIC 74.3 (39.7) 70.3 (40.7) 66.4 (54.9) 80.7 (36.5) 88.7 (29.4) Mental LC 61.7 (11.8) 75.0 (17.1) 77.3 (18.3) 83.3 (16.2) 85.1 (16.6) 0.558 SIC 62.0 (10.9) 72.1 (18.9) 74.5 (18.7) 81.2 (18.4) 83.4 (17.4) Vitality LC 54.1 (11.0) 59.6 (22.4) 52.1 (21.1) 67.8 (20.1) 73.5 (20.4) 0.767 SIC 53.8 (12.2) 58.4 (22.9) 51.8 (21.6) 66.9 (22.6) 72.7 (21.7) Pain LC 56.5 (19.5) 55.6 (22.5) 52.2 (21.7) 74.7 (20.2) 82.4 (21.5) 0.429 SIC 54.6 (17.1) 55.9 (24.6) 46.4 (21.9) 69.3 (23.8) 83.1 (21.4) General health LC 56.1 (11.7) 69.7 (17.3) 71.8 (19.3) 74.9 (22.0) 76.3 (21.2) 0.457 SIC 57.4 (11.3) 65.1 (19.2) 70.1 (20.1) 72.5 (21.5) 76.4 (19.2) Health change LC 57.7 (21.2) 57.7 (21.2) 62.0 (26.9) 76.7 (23.9) 77.1 (24.4) <0.001* SIC 55.4 (20.4) 55.4 (20.4) 53.5 (27.5) 64.6 (25.1) 71.5 (27.2) GIQLI Physical LC 2.79 (0.76) 2.82 (0.73) 2.78 (0.75) 3.20 (0.62) 3.31 (0.59) 0.790 SIC 2.95 (0.74) 2.67 (0.83) 2.69 (0.75) 3.14 (0.73) 3.30 (0.63) Gastrointestinal LC 3.01 (0.59) 3.01 (0.54) 3.22 (0.48) 3.46 (0.41) 3.50 (0.42) 0.247 SIC 3.12 (0.58) 3.13 (0.55) 3.22 (0.45) 3.46 (0.46) 3.52 (0.40) Social LC 2.89 (0.48) 2.82 (0.42) 2.81 (0.52) 2.93 (0.37) 2.97 (0.29) 0.056 SIC 2.90 (0.42) 2.82 (0.43) 2.76 (0.56) 2.85 (0.50) 2.85 (0.38) Mental LC 2.55 (0.55) 2.59 (0.45) 2.88 (0.41) 3.04 (0.35) 3.07 (0.37) 0.561 SIC 2.65 (0.49) 2.58 (0.55) 2.74 (0.45) 2.99 (0.47) 3.04 (0.44) Total LC 102.4 (17.0) 102.6 (14.8) 108.5 (15.0) 116.4 (11.9) 118.3 (11.7) 0.607 SIC 106.7 (14.9) 104.5 (16.0) 107.4 (14.0) 116.7 (13.2) 118.0 (11.1) BIQ Body image LC 6.42 (1.98) – – 6.03 (1.90) – 0.530 SIC 6.26 (1.89) – – 5.85 (1.35) – Cosmetic LC – – – 18.38 (3.88) – 0.100 SIC – – – 17.52 (3.55) – Self-confidence LC 6.95 (1.27) – – 7.68 (1.21) – 0.647 SIC 7.02 (1.28) – – 7.49 (1.15) – * significant difference Subgroup analysis t df p 5 Table 5 Comparison of GIQLI, SF-36 and BIQ scores in minimal invasive laparoscopic (LC) and small-incision cholecystectomy (SIC) procedures versus converted (LC and SIC) procedures (mean scores and SD)   Preoperative Postoperative P value day 1 2 weeks 6 weeks 12 weeks SF-36 Physical min-inv 79.9 (21.3) 50.1 (30.9) 67.3 (22.1) 83.5 (21.1) 87.6 (18.9) 0.046* conv 82.3 (17.5) 31.6 (24.9) 45.5 (22.6) 79.6 (19.3) 87.8 (14.6) Social min-inv 43.2 (15.5) 76.7 (21.3) 69.9 (24.1) 85.1 (20.9) 90.9 (18.1) 0.214 conv 41.7 (18.3) 70.1 (21.9) 55.1 (29.0) 76.1 (24.7) 93.2 (13.8) Role physical min-inv 60.2 (43.4) 54.0 (44.5) 27.9 (36.3) 61.3 (41.7) 79.9 (35.2) 0.415 conv 46.9 (46.8) 43.1 (43.9) 31.0 (87.6) 55.0 (44.1) 81.8 (37.1) Role emotion min-inv 74.9 (39.0) 72.1 (38.8) 67.4 (41.5) 82.1 (34.6) 89.3 (28.1) 0.373 conv 66.7 (42.8) 56.5 (45.4) 66.7 (93.7) 76.7 (40.6) 83.3 (32.1) Mental min-inv 61.8 (11.6) 73.8 (17.9) 76.6 (17.5) 82.7 (16.4) 84.9 (15.9) 0.413 conv 62.6 (9.1) 70.8 (19.5) 69.0 (25.5) 77.1 (24.4) 78.6 (23.8) Vitality min-inv 54.0 (11.9) 59.5 (22.8) 53.1 (21.1) 67.8 (21.4) 73.3 (20.6) 0.180 conv 53.2 (8.8) 55.0 (21.2) 41.6 (21.1) 63.3 (21.6) 71.1 (24.9) Pain min-inv 55.6 (18.4) 56.5 (23.7) 50.4 (22.1) 72.5 (22.3) 82.9 (21.7) 0.038* conv 55.2 (17.7) 49.6 (22.2) 37.1 (17.4) 65.4 (22.4) 81.9 (18.5) General health min-inv 56.8 (11.4) 68.2 (18.1) 72.0 (19.4) 74.2 (21.3) 76.9 (19.7) 0.136 conv 56.3 (12.4) 59.7 (19.6) 61.0 (20.2) 67.8 (25.1) 72.2 (23.3) Health change min-inv 56.8 (20.8) 56.8 (20.8) 58.8 (27.5) 71.7 (24.9) 74.9 (26.3) 0.066 conv 54.2 (20.4) 54.2 (20.4) 46.3 (24.7) 56.3 (24.2) 67.1 (23.6) GIQLI Physical min-inv 2.90 (0.72) 2.78 (0.76) 2.79 (0.71) 3.19 (0.65) 3.33 (0.60) 0.007* conv 2.67 (0.96) 2.40 (0.96) 2.20 (0.87) 2.96 (0.91) 3.10 (0.71) Gastrointestinal min-inv 3.09 (0.57) 3.10 (0.54) 3.23 (0.47) 3.47 (0.43) 3.52 (0.39) 0.052 conv 2.89 (0.68) 2.89 (0.56) 3.08 (0.37) 3.42 (0.50) 3.46 (0.50) Social min-inv 2.89 (0.46) 2.83 (0.42) 2.83 (0.51) 2.90 (0.43) 2.92 (0.35) 0.003* conv 2.90 (0.35) 2.75 (0.45) 2.35 (0.62) 2.74 (0.58) 2.85 (0.35) Mental min-inv 2.60 (0.53) 2.58 (0.50) 2.84 (0.41) 3.04 (0.38) 3.06 (0.38) 0.031* conv 2.63 (0.45) 2.64 (0.53) 2.48 (0.57) 2.81 (0.70) 2.96 (0.63) Total min-inv 104.9 (16.0) 104.3 (15.0) 108.9 (14.3) 117.1 (11.5) 118.4 (11.0) 0.020* conv 101.4 (17.0) 97.8 (17.8) 98.5 (13.3) 111.2 (19.5) 115.8 (14.0) BIQ Body image min-inv 6.31 (1.80) - - 5.75 (1.27) - <0.001* conv 6.60 (2.78) - - 7.55 (3.04) - Cosmetic min-inv - - - 18.27 (3.54) - <0.001* conv - - - 14.86 (3.97) - Self-confidence min-inv 7.08 (1.16) - - 7.60 (1.13) - 0.064 conv 6.31 (1.83) - - 7.38 (1.60) - * significant difference; min-inv: minimal invasive procedures (LC and SIC); conv: converted procedures (LC and SIC) F df p F df p F df p p p p F df p Discussion We have used both generic and disease-specific health status questionnaires and a body image questionnaire to evaluate the effect of LC versus SIC in patients having cholecystectomy for symptomatic cholecystolithiasis. No differences were found between laparoscopic and small-incision cholecystectomies (applying intention-to-treat). However, with regard to minimal invasive or converted procedures, we found significant differences in the ‘physical’ subscales in both SF-36 and GIQLI as well as differences in body image in favour of minimal invasive procedures. The fact that significant differences were found in the ‘physical’ subscales in both questionnaires illustrates construct validity between both health status instruments. Literature 18 20 18 19 20 21 18 19 20 In our study, no significant differences were found between LC and SIC using both generic and disease-specific health status as well as body image with response in approximately 80% of patients. The response rate of 77.4% at 3 months follow-up may represent a possible source of bias. However, the nonresponders were comparable to those who remained in the study with regard to complications, operative time, hospital stay, return to work, and baseline scores of questionnaires. Moreover, our response rate is in line with the response rates in the studies of Barkun et al. (58%) and McMahon et al. (78%). We conclude that there are no differences between both operative techniques regarding health status. The only exception is that in the SF-36 subscale perceived health change we found a difference between LC and SIC, which appeared to be caused by the scores at 2 and 6 weeks postoperatively and disappeared at 3 months follow-up. LC patients reported a larger health change. However, in the evaluation of 17 aspects of health status, only one difference was found. Moreover, this difference in perceived health change was not reflected in an earlier return to work in LC. In contrast, SIC patients returned to work quicker than LC patients, although this different was not significant. Therefore, our overall interpretation is that there are no differences between LC and SIC. The comparable ‘physical’ subscales in SF-36 and GIQLI, which are supposed to measure the same effect, are both significantly different in the minimal invasive versus conversions comparison illustrating construct validity of both questionnaires. Subscales on different subjects in the questionnaires illustrate divergent validity. Significant differences between minimal invasive and converted procedures illustrate that the questionnaires used are able to measure what they are intended to do. Conclusion In our randomised trial with adequate generation of the allocation sequence, concealment of allocation, blinding, and follow-up we used both a generic and a disease-specific questionnaire in addition to a body image questionnaire. There is no significant difference in health status measured with SF-36, GIQLI, and BIQ between laparoscopic and small-incision cholecystectomy (applying the intention-to-treat principle). Additional calculations showed a significant difference between minimal invasive LC or SIC procedures and procedures converted to the classical open cholecystectomy.