Clinical trial NCT01339325: Laparo-endoscopic Single Site (LESS) Cholecystectomy Versus Standard LAP-CHOLE
Official title: Laparo-endoscopic Single Site Cholecystectomy Versus Standard Laparoscopic Cholecystectomy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Cholelithiasis
Keywords: Laparo-endoscopic single site cholecystectomy
Quality of Life
Postoperative Pain
Cosmetics
Complication
Lead sponsor: San Giovanni Addolorata Hospital
Sponsor class: OTHER
First posted: 2011-04-20
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of this study is to assess possible differences between the LESS approach and the standard laparoscopic approach to cholecystectomy. In particular, the Postoperative Quality of Life (QoL) will be investigated by analyzing the followings: length of hospital stay (LoS), postoperative pain, cosmetics and the results of SF 36 questionnaire. Furthermore, operative time, conversion to standard LC rate, difficulty of exposure, difficulty of dissection, and complication rate will be compared.

Detailed description: The aim of this study is to assess possible differences between the LESS approach and the standard laparoscopic approach to cholecystectomy. In particular, the Postoperative Quality of Life (QoL) will be investigated by analyzing the followings: length of hospital stay (LoS), postoperative pain, cosmetics and the results of SF 36 questionnaire. Furthermore, operative time, conversion to standard LC rate, difficulty of exposure, difficulty of dissection, and complication rate will be compared.

Altman nomograms were used to calculate the presumed sample size of an actual RCT, arbitrarily assuming a most likely small standardized difference (0.3). With a significant criterion set at 0.05, using a two-tailed test, the number of patients per group, required to have a 90% power is \~500. Therefore, it was decided to carry on a pilot trial, enrolling 40 patients (20 each group), to assess differences in any of the end-points and tailoring the sample size of the larger multicenter RCT accordingly.

This dual-institutional prospective, randomized pilot trial was conducted during 2009 obtaining information on the power and sample size needed for a planned multicenter randomized control trial. Our results showed that Quality of life data concerning LESS cholecystectomy are somewhat controversial: cosmetics and SF36 role emotional parameter significantly improved, no differences were found in length of hospital stay, early postoperative pain (same day of surgery) was higher but no impact on need for pain-relieving medications was found. Altman nomograms were used again to calculate the presumed sample size of an actual RCT based on the differences found on our initial results. With a significant criterion set at 0.05, using a two-tailed test, the number of patients per group, required to have a 90% power in this multicenter RCT is \~180 patients.

Study design Randomization is performed preoperatively and stratification is performed intraoperatively, after visualization of the operative field. Patients are randomized to one of three groups: LESS cholecystectomy blind, standard LC, LESS cholecystectomy not blind. Patients are stratified into 3 groups: Nassar grade I, II, III, according to the grade of difficulty of cholecystectomy (Nassar score) assessed at the initial inspection of the operating field.

Patients of the first two groups do not know the treatment received until their discharge. A large drape is used to cover the abdomen after surgery, thus hiding the surgical wounds. Patients of the LESS cholecystectomy not blind group are aware of the procedure they undergo. The third arm is intended to better evaluate the influence of psychological factors on postoperative pain, cosmetics and quality of life.

All operations are performed by high-skilled laparoscopic surgeons (one each institution) with over 15-year experience in advanced laparoscopic surgery.

Difficulty (impaired) of exposure and difficulty of dissection are assessed subjectively by the operating surgeon and scored 1 to 4, being 1 "no difficulties", 4 "the most difficult" with need for conversion.

Perioperative care is similar in all patients and in all institutions. An independent physician will assess the patient postoperatively in each institution. Postoperative pain is evaluated with a visual analogue scale (VAS) from 1 to 10, with 1 being "the least" pain, 10 "the most" pain, on the day of surgery, on postoperative day 1, 2 (discharge) and at 1-month follow-up. Pain is also deduced from the assumption of pain relieving medications. Patients will receive pain medications only on demand and these will be given in incremental strength beginning with peripheral analgesics as Non-Steroidal Anti-Rheumatic agents (NSAR).

Individual satisfaction for the cosmetic result is evaluated with a visual analogue scale (VAS) from 0 to 100% with 0 being "the worse" result, 100 "the best" one. Cosmetics is also evaluated by measuring the length of umbilical incision at the end of the operation in all study groups. The incision length is measured after gallbladder removal (during standard LC the incision may be enlarged to allow the passage of thick gallbladder or bigger stones).

QoL is assessed at the time of surgery and further assessed at postoperative month 1 by the SF36 questionnaire.

Randomization Randomization is performed preparing three sets of 30 numbered, opaque, sealed envelopes, the envelops of each set containing indications for 10 LESS cholecystectomies, 10 standard LC and 10 LESS cholecystectomies not blind. One set of envelopes is kept at each involved Institution. The envelopes are opened in numeric order for each patient by an assistant not involved in the surgical operations, right before surgery. The surgeons perform a standard LC or a LESS cholecystectomy (blind or not blind) as indicated on the sheet inside the envelopes.

Data analyses Data are analysed using the software XLSTAT Version 2009.5.01 (Addinsoft). An "intent-to-treat" analysis will be performed.

Patients demographics across the treatment groups are compared by chi-square test for categorical measures, and by t-test for continuous data. Mann-Whitney U test is used to compare LoS, postoperative pain VAS, cosmetics VAS, length of skin incision, 8 parameters of SF36, operating time, difficulty of exposure, difficulty of dissection in the two arms. Chi-square test is used to compare conversion rate and administration of pain medication, which is dichotomized as yes or no, in the three arms. All variables are significant at p\< 0.05. Logistic model results are reported as odds ratios, two-sided 95% confidence intervals, and p values.

Eligibility criteria: Inclusion Criteria:

* age 18-75
* BMI \< 35
* no previous upper GI or right colonic surgery with severe adhesions gallstones with absence of clinical signs of acute cholecystitis, bile duct stones or pancreatitis.
* ASA I-III
* Nassar grade of difficulty in performing a laparoscopic cholecystectomy I-III
* diagnosis: cholelithiasis

Exclusion Criteria:

* cholecystitis
* existence of common duct stones
* presence of biliary cancer
* Previous abdominal surgery on organs of the supramesocolic space

Primary outcomes:
measure: Postoperative Quality of Life (QoL)
timeFrame: one month
Secondary outcomes:
measure: operative time
timeFrame: day 1
measure: conversion rate to standard LC
timeFrame: day 1
measure: surgeon perception of difficulty of exposure measured with a Visual Analog Scale (VAS) with 0 to the least difficult and 5 to the most difficult
timeFrame: day 1
measure: surgeon perception of difficulty of dissection measured with a Visual Analog Scale (VAS) with 0 to the least difficult and 5 to the most difficult
timeFrame: day 1
measure: complication rate
timeFrame: one month
Other outcomes:
Locations:
city: Rome
country: Italy
facility: San Giovanni Hospital
state: Lazio
Study officials:
affiliation: San Giovanni Hospital
name: Marco Maria Lirici, FACS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Steinemann DC, Raptis DA, Lurje G, Oberkofler CE, Wyss R, Zehnder A, Lesurtel M, Vonlanthen R, Clavien PA, Breitenstein S. Cosmesis and body image after single-port laparoscopic or conventional laparoscopic cholecystectomy: a multicenter double blinded randomised controlled trial (SPOCC-trial). BMC Surg. 2011 Sep 12;11:24. doi: 10.1186/1471-2482-11-24.