Laparoscopic versus minilaparotomy cholecystectomy: a randomised trial

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A515. Barnes PJ. Antiinflammatory therapy in asthma. Annu Rev Med 1993; 44: 229-49. Liu SF, Adcock IM, Old RW, Barnes PJ, Evans T. Lipopolysaccharide treatment in vivo induces widespread expression of inducible oxide synthase mRNA. Biochem Biophys Res Commun 1993; 196: 1208-13. Archer S. Measurement of nitric oxide in biological models. FASEB J 1993; 7: 349-60. Kobzik L, Drazen J, Bredt D, et al. Nitric oxide synthase (NOS) in the lung: immunologic and histochemical localization in human and rat tissue. Am Rev Respir Dis 1993; 147: A515.

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Nakayama DK, Geller DA, Lowenstein CJ, et al. Cytokines and lipopolysaccharide induce nitric oxide synthase in cultured rat pulmonary artery smooth muscle. Am J Respir Cell Mol Biol 1992; 7: 471-76. 10 Robbins RA, Hamel FG, Floreani AA, et al. Bovine bronchial epithelial cells metabolize L-arginine to L-citrulline: possible role of nitric oxide synthase. Life Sci 1993; 52: 709-16. 11 Jorens PG, van Overveld FJ, Bult H, Vermeire PA, Herman AG. L-arginine-dependent production of nitrogen oxides by pulmonary macrophages. Eur J Pharmacol 1991; 200: 205-09. 12 Wright CD, Mulsch A, Busse R, Osswald H. Generation of nitric oxide by human neutrophils. Biochem Biophys Res Commun 1989; 160:

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CD, Barnes PJ. Nitric oxide is the endogenous neurotransmitter of bronchodilator nerves in human airways. Eur J Pharmacol 1992;; 210: 221-22. 14 Ward JK, Belvisi MG, Fox AJ, et al. Modulation of cholinergic neural bronchoconstriction by endogenous nitric oxide and vasoactive intestinal peptide in human airways in vitro. J J Clin Invest 1993; 92: 736-42. 15 Dinh-Xuan AT. Endothelial modulation of pulmonary vascular tone. Eur Respir J 1992; 5: 757-62. 16 Kuo H-P, Liu SF, Barnes PJ. The effect of endogenous nitric oxide on neurogenic plasma exudation in guinea pig airways. Eur J Pharmacol 1992; 221: 385-88.

Laparoscopic versus minilaparotomy cholecystectomy: a

randomised trial

Summary Although laparoscopic cholecystectomy has rapidly become routine practice in the UK, there has been no rigorous comparison of it with open cholecystectomy. In our trial, 302 patients were randomised to laparoscopic or minilaparotomy cholecystectomy. Recovery after surgery was assessed by length of hospital stay, outpatient review at 10 days and 4 weeks, and patient questionnaires 1, 4, and 12 weeks after

to Compared minilaparotomy cholecystectomy, in results shorter laparoscopic cholecystectomy hospital stay, less postoperative dysfunction, and quicker return to normal activities, but is more costly.

Lancet 1994; 343: 135-38

Introduction

operation time was 14 min shorter for minilaparotomy, while median post-operative hospital stay was 2 days shorter after laparoscopic cholecystectomy. The hospital costs were about £400 greater for the laparoscopic procedure. Laparoscopic patients returned to work in the home sooner; at 1 week, they had better physical and social functioning, were less limited by physical problems, and had less pain and depression. At 4 weeks, only physical functioning and depression scores were better in the laparoscopic group, and by 3 months there were no differences. Laparoscopic

Laparoscopic cholecystectomy has rapidly replaced open cholecystectomy as the standard treatment for symptomatic cholelithiasis in the UK. The perceived advantages of laparoscopic cholecystectomy are reduced hospital stay and a more rapid return to normal activity, but audit has shown an increased incidence of bile duct injury, 1,2 and other serious complications including vascular injury and viscus perforation.1,3 Surgeons have been reluctant to conduct clinical trials comparing conventional with laparoscopic cholecystectomy. However, a small transverse subcostal incision (minilaparotomy) for open cholecystectomy results in more rapid post-operative recovery than a standard

satisfied with the appearance of their scars. The incidence of complications after both procedures was 20%.

laparoscopic following cholecystectomy.

surgery. The

mean

patients

were more

incision.4-6 We did

a

randomised trial and

to

compare outcome

minilaparotomy

Patients and methods University Departments of Surgery, Western Infirmary and Royal Infirmary, Glasgow, UK (A J McMahon FRCS, J N Baxter FRACS, J R Anderson FRCS, G Ramsay FRCS, P J O’Dwyer FRCS); Health Services Research Unit, University of Aberdeen, UK (I T Russell PhD, S Ross Mphil); Department of Surgery, Southern General Hospital, Glasgow, UK (G Sutherland FRCS); Department of Surgery, Gartnavel General Hospital, Glasgow, UK (D Galloway FRCS); and Department of Surgery, Crosshouse Hospital, Kilmarnock, UK (C G Morran FRCS) Correspondence to: Mr Patrick J O’Dwyer, University Department of Surgery, Western Infirmary, Glasgow G11 6NT, UK

7 consultant surgeons in 5 hospitals in Glasgow, Aberdeen, and Kilmarnock, UK participated in this trial, which was approved by

the relevant ethical committees. All surgeons had previous experience of laparoscopic cholecystectomy and all except 1 had assisted at or done > 30 procedures. Recruitment began in August 1991, and was completed in March 1993. All patients undergoing elective cholecystectomy for symptomatic cholelithiasis without common bileduct stones or extensive previous upper abdominal surgery (eg, gastrectomy) were eligible. Patients with abnormal liver function tests or a dilated common bileduct on ultrasound

135

recruited into the trial only if a preoperative cholangiogram normal. Patients giving informed consent were randomised on the day before operation by the use of numbered sealed envelopes,

were

was

stratified by surgeon.

Laparoscopic cholecystectomy was done by a four-trocar technique with electrocautery dissection. Minilaparotomy cholecystectomy was through a 5 to 10 cm transverse subcostal incision. In both groups, patients received antibiotic prophylaxis, subcutaneous heparin, and local anaesthetic wound infiltration at the end of the procedure. A consultant was present at all operations. Only one surgeon had a policy of doing routine cholangiography; the others did so only when there was a suspicion of bile duct stones at operation. Postoperative pain, patient-controlled morphine consumption, pulmonary function, and O2 saturation were assessed for 48 hours after surgery in the first year of the trial (132 patients) and the results are reported elsewhere.7 Before hospital discharge, patients had to tolerate a normal diet, be able to dress themselves, be fully mobile around the ward, require only oral analgesia, and be satisfied they could manage at home. Patients were reviewed at the outpatient clinic at 10 days and 4 weeks post-operatively. Patients completed postal questionnaires at 1, 4, and 12 weeks after operation with reminders for non-responders 2 and 4 weeks after the last two questionnaires. The questions were about return to normal activities, a modified version of the Short Form 36 (SF-36) health survey questionnaire and the Hospital Anxiety and Depression Scale (HADS).9 Questions 9 (i-ix) and 10 in the SF-36 were omitted to avoid repetition of similar questions in HADS. Finally, patients were asked to grade their satisfaction with the operation and the appearance of the operation scars on 5-point scales. Costs Costs

Postoperative hospital stay (days) Figure 1: Postoperative hospital stay after cholecystectomy greater than 10 cm was necessary in 14 patients (10 %); 4 had severe cholecystitis or chronic empyema, 4 had morbid obesity, 2 bileduct stones, 2 bleeding, 1 a cholecystocholedochal fistula, and 1 an intrahepatic gallbladder. Complications of cholelithiasis (mucocoele or chronic empyema) were found in 43 (14%) of 299 patients. One elderly minilaparotomy patient with a large

cholecystoduodenal fistula was treated by cholecystostomy

hospitals involved (Western Infirmary and Royal Infirmary, Glasgow) were used to estimate average theatre (396 per hour) and ward ( £ 73 per day) costs. The National Health Service cost of hospital admission for each patient was then estimated from recorded time in theatre, hospital stay, and additional tests or treatment. Cost did not include previous investigation or outpatient follow-up. at

the

two

main

Statistical methods The trial intended to recruit 300 patients over 2 years. With a significance level of 5%, such a sample would have 80% power to detect differences between laparoscopic and minilaparotomy groups greater than one third of the standard deviation of normally-distributed outcome measures. Results were analysed by intention to treat: all patients requiring conversion to standard cholecystectomy were included. Normally-distributed data were analysed by the t test, and other quantitative data by the Mann-Whitney U test. Patients’ ratings of outcome were analysed by the X2 test for linear trend.

and stone removal alone. The mean operation time from skin incision to closure was significantly shorter in the minilaparotomy group 57 (standard deviation [SD] 24 min) vs 71 (SD 20); t test p < 0-001. Figure 1 shows that the median postoperative hospital stay of 2 days after laparoscopic cholecystectomy was significantly shorter than that of 4 days after minilaparotomy (Mann-Whitney U test p < 0-001).

Post-operative pain and pulmonary function Laparoscopic cholecystectomy was associated with lower linear analogue pain scores (median 40 vs 59, p < 0’001), lower patient-controlled morphine consumption (median 22 vs 40 mg, p < 0-001), a smaller reduction in postoperative pulmonary function (mean peak expiratory flow rate 64% of pre-operative value vs 49%, p<0001) and better O2 saturation (mean 92’9% vs 91,2%, p < 0’01) than minilaparotomy cholecystectomy 24 h post-operatively.7

Results Informed consent to randomisation was obtained from 302 of 311 eligible patients. The 9 refusers had laparoscopic cholecystectomy. 3 randomised patients did not undergo cholecystectomy; 2 were unexpectedly found to have liver metastases, and another to have severe cirrhosis. Randomisation produced two groups with similar demographic (age, sex, and employment status), physical (height and weight), and clinical (duration of symptoms, indication for American Society of surgery, fitness and classification, Anaesthesiology’s physical characteristics. operative findings) 15 (10%) patients randomised to laparoscopic to conversion required open cholecystectomy cholecystectomy; 7 had severe cholecystitis or chronic empyema, 3 unclear anatomy, 2 dense intra-abdominal adhesions, 1 bileduct stones, 1 bleeding, and 1 equipment failure. In the mini laparotomy group, the median incision length was 7 cm (interquartile range 5-9 cm). An incision 136

Table 1:

Postoperative complications

in a minilaparotomy patient for a subvesical leak shown by endoscopic retrograde cholangiography (ERCP). 1 patient developed septicaemic shock post-operatively and had a negative re-laparotomy. 3 patients required transfusion post-operatively for bleeding. Re-operation was required in 1 patient for adhesive obstruction at 1 month. There was 1 death from myocardial infarction on the second post-operative day. In the laparoscopic group, a patient had jaundice 1 week after cholecystectomy, and ERCP showed complete division of the common hepatic duct; this was repaired and the patient remains well 6 months later. Another patient had a bile leak and jaundice postoperatively: the bile was drained percutaneously, ERCP showed a subvesical bileduct leak and a stone in the common bileduct, which was removed endoscopically. 1 patient had biliary peritonitis 2 weeks postoperatively from a subvesical bileduct leak which required laparotomy and drainage; in another, a cystic bileduct leak was treated by percutaneous drainage and endoscopic placement of a biliary stent. 3 patients required transfusion post-operatively for bleeding.

required

bileduct

Patient

(worst pain)

no pain)

Pain

score

(SF-36)

Figure 3: Pain scores one week after cholecystectomy

Complications The incidence of both major and minor complications was similar in both groups (table 1). In the minilaparotomy group, two minor bileduct injuries occurred: a 3 mm transverse incision in the common hepatic duct (repaired immediately with two interrupted sutures), and a similar injury at the junction of the cystic and common bileducts was managed by inserting a T tube. Both patients remain well one year later. Percutaneous ultrasound drainage was

questionnaires

The response rate to the 1, 4, and 12 week questionnaires was 78%, 88%, and 81% respectively in both groups. Laparoscopic patients returned more quickly to leisure activities (median 7 days vs 12; Mann-Whitney U test work in the home (figure 2; 10 days vs 15; p<0-01), p < 0001) and social activities (14 days vs 21; p<0-001). However, there was no difference in the time to return to sexual activity (21 days) or paid employment (5-6 weeks). In both groups SF-36 and HADS scores improved from the 1st to the 12th postoperative week. One week after surgery, laparoscopic patients had significantly-better physical functioning (57 vs 43 out of 100; Mann-Whitney U test p < 0’05) and social functioning (74 vs 67 out of 100; p < 005), less role limitation due to physical problems (13 vs 0% p < 0-01), less pain (figure 3: 67 vs 44% p < 0-001), and less depression (median 2 out of 21 vs 3; p<0-01) than minilaparotomy patients. At 4 weeks, laparoscopic patients still had better physical functioning (median 67 out of 100 vs 60; p < 0’05) and less depression (median 1 out of 21 vs 2; but by 12 weeks there were no significant p<0’05), differences between the groups in any of the patient-

reported scores. Patients’ ratings of

outcome after cholecystectomy are in table 2. At 12 shown weeks, over 90% of patients in both groups thought the outcome of their operation was "good"

"excellent". Nevertheless, laparoscopic patients were satisfied with the appearance of their scars (X2 for linear trend p < 0 05).

or

more

*x’test for linear trend (laparoscopic vs mmilaparotomy) p 0 05). Table 2: Patients’ ratings of outcome after cholecystectomy

137

ECG

electrocardiogram. Table 3: Cost per patient for =

cholectstectomy

Costt Time and thus theatre

cost was higher for laparoscopic cholecystectomy (table 3). Hospital stay and thus ward cost was higher for minilaparotomy. The mean total cost per patient was jC396 greater for the laparoscopic method (95 % CI 328-465). If disposable instruments had not been used, the difference in mean cost would have been £93 (95% CI 25-162).

Discussion

Only one other randomised trial of laparoscopic cholecystectomy has been reported in English-language journals.1 Both studies found a moderate advantage of the laparoscopic method over minilaparotomy in hospital stay and duration of convalescence. Although the Canadian laparoscopic patients reported earlier improvements in quality of life, the difference was not statistically significant probably because of the small sample size (62 patients). Nevertheless, the results are consistent with those of the present study, in which laparoscopic patients reported many significant differences in health at 1 week, fewer differences at 1 month, and no differences by 3 months. The median hospital stay for laparoscopic cholecystectomy in our study is similar to that reported from other European centres," whereas a median stay of one day is more typical for American centres.12 While outpatient minilaparotomy cholecystectomy has been reported,’ the median post-operative stay of 4 days after minilaparotomy cholecystectomy in this study is comparable with that reported in other studies. 10,13 In this study, the patients took on average between 1 and 2 weeks to return to normal activities after laparoscopic cholecystectomy-similar to that reported." Return to normal activity for open cholecystectomy has not been accurately measured but is commonly perceived to be 6 weeks or more. In this study, the patients returned to normal activities between 10 days and 3 weeks after minilaparotomy cholecystectomy. In this study, minilaparotomy was cheaper than laparoscopic cholecystectomy, and would still have been cheaper if re-usable instruments had been used for laparoscopic surgery. Conflicting findings from other studies14,15reflect differences in operation time and hospital stay-the two main determinants of cost. This study has shown a similar incidence of complications after both procedures. However, only rigorous large-scale audit can accurately estimate the incidence of complications. Audit has shown a higher incidence of bileduct injury after laparoscopic cholecystectomylcompared with open cholecystectomy.16 Furthermore, the bileduct injuries from laparoscopic cholecystectomy tend to be more extensive and higher in the duct system17 than those from open cholecystectomy, 138

thus reducing the chance of a successful outcome from reconstruction. In the published results of over 2500 minilaparotomy cholecystectomies there have been only two bileduct injuries.18 The two injuries occurring during our trial were both minor, and did not cause significant morbidity to the patient. In conclusion, this study has shown that laparoscopic cholecystectomy confers benefits on patients in the form of reduced postoperative pain and pulmonary dysfunction7 shorter hospital stay, and earlier return to normal activities. However, the laparoscopic operation was more expensive. It seems likely that, as surgeons became more experienced, the relative benefit to patients will increase, while the relative cost will decrease. Rigorous large-scale audit is needed to ensure that the apparent advantages of laparoscopic cholecystectomy are maintained in the long term.

We thank the other surgical consultants in the Western and Royal Infirmaries for their help with this study; Ken Buckingham for economic advice; and Jennifer Birdsall of the Health Services Research Unit, Aberdeen, for research support. Supported by a grant from Chief Scientist Office of the Home and Health Department of the Scottish Office, Edinburgh, UK (ref no: K/OPR/2/2/D6).

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3 4 5 6

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