The American Journal of Surgery 214 (2017) 920e930

Contents lists available at ScienceDirect

The American Journal of Surgery

journal homepage: www.americanjournalofsurgery.com

Review

Risk factors for conversion of laparoscopic cholecystectomy to open

surgery e A systematic literature review of 30 studies
Alan Shiun Yew Hu a, *, R. Menon a, R. Gunnarsson a, b, c, A. de Costa a
a
Cairns Clinical School, College of Medicine and Dentistry, James Cook University, QLD, 4870, Australia
b €
Research and Development Unit, Primary Health Care and Dental Care, Narhalsan, Southern Alvsborg €stra Go
County, Region Va €taland, Sweden
c
Department of Public Health and Community Medicine, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Sweden

a r t i c l e i n f o a b s t r a c t

Article history: Background: The study aims to evaluate the methodological quality of publications relating to predicting
Received 12 December 2016 the need of conversion from laparoscopic to open cholecystectomy and to describe identified prognostic
Received in revised form factors.
10 July 2017
Method: Only English full-text articles with their own unique observations from more than 300 patients
Accepted 16 July 2017
were included. Only data using multivariate analysis of risk factors were selected. Quality assessment
criteria stratifying the risk of bias were constructed and applied.
Keywords:
Results: The methodological quality of the studies were mostly heterogeneous. Most studies performed
Laparoscopic cholecystectomy
Risk factors
well in half of the quality criteria and considered similar risk factors, such as male gender and old age, as
Open cholecystectomy significant. Several studies developed prediction models for risk of conversion. Independent risk factors
Conversion to open surgery appeared to have additive effects.
Biliary tract surgical procedure Conclusion: A detailed critical review of studies of prediction models and risk stratification for conver-
Nomogram sion from laparoscopic to open cholecystectomy is presented. One study is identified of high quality with
a potential to be used in clinical practice, and external validation of this model is recommended.
© 2017 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND
license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 921
2. Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 921
2.1. Protocol and registration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 921
2.2. Eligibility criteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 921
2.3. Search strategy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 921
2.4. Methodological quality . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 921
3. Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 921
3.1. Quality assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 921
3.2. Risk factors and their association with highest possible quality of the studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 921
3.2.1. Variables evaluated in high quality study . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 922
3.2.2. Variables evaluated in intermediate quality studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 922
4. Other risk factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 923
4.1. Variables evaluated in low quality studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 927
4.2. Risk score and predictive models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 927
5. Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 927
5.1. Unconventional findings and significance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 928
5.2. Prediction models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 928

* Corresponding author.
E-mail addresses: alan.hu@my.jcu.edu.au (A.S.Y. Hu), rohit.menon@my.jcu.edu.
au (R. Menon), ronny.gunnarsson@jcu.edu.au (R. Gunnarsson), alan.decosta@jcu.
edu.au (A. de Costa).

http://dx.doi.org/10.1016/j.amjsurg.2017.07.029
0002-9610/© 2017 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
 A.S.Y. Hu et al. / The American Journal of Surgery 214 (2017) 920e930 921

6. Strength of this review . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 928

7. Limitation of this review . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 928
8. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 928
Conflicts of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 928
Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 929
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 929

1. Introduction observations from more than 300 patients which presented their
own unique observations, and with multivariate statistical tech-
One of the most common causes of abdominal pain is the niques adjusting for covariates, were included. No restrictions were
presence of gallstones.1 Cholecystectomy is the only effective made regarding the time of publication.
management of symptomatic gallstones, with 93% of gallbladder
disease problems referred to surgeons.2 Open cholecystectomy 2.3. Search strategy
(OC) has been widely replaced by laparoscopic cholecystectomy
(LC).3 However, current literature suggests that the rate of intra- Two investigators (AH and RM) performed the systematic search
operative conversion from LC to OC is 1%e15%,4e6 and that con- through PubMed (Table 1) and Scopus (Table 2) on June 8, 2016. The
version is known to increase perioperative time, complication rates, two investigators screened publication titles and abstracts inde-
perioperative costs, the length of hospital stay, and hospital pendently. Discrepancies were adjudicated by a third review author
charges.7,8 Conversion is also associated with complications (AdeC). Full-text articles were then reviewed. An additional
including death, bile duct injury, bile leak, or bleeding, requiring snowball search found the two review articles as discussed earlier.
reoperation or transfusion.9 It is, therefore, essential to identify risk
factors for conversion to allow for safer procedures and better 2.4. Methodological quality
surgical planning. A systematic assessment of these factors pre-
operatively allows determination of whether OC surgery should Eight measures were developed for this review to assess
be performed initially, avoiding the potential complications methodological quality (Table 3).
brought through an intraoperative conversion from LC to OC.
Further, effective conversion prediction models allow patients the
3. Results
right to be better informed of such risks before they give consent.
Several factors encourage a new review of the literature on LC to
Sixty-six articles were read in full-text, with 30 meeting the in-
OC conversion. Two previous reviews agreed on only two important
clusion criteria (Fig. 1). Two studies16,17 were subsequently excluded
risk factors when considering conversion, namely, male gender and
after thorough examination as they were found to use data from
old age6,10; Rothman et al.’s10 recent study focused on only 10 articles
previous studies.18,19 Only variables that were statistically signifi-
for inclusion in their meta-analysis. Further, literature searches in
cant in the final multivariate regression model are presented.
previous reviews were conducted in 2005 and in 2014 respectively.
The gap between those studies and current date, and the presence of
3.1. Quality assessment
new critical studies published in recent years, warrant a new
review.11e14 Furthermore, the risk factor of body temperature, was
Our review found only one publication was of high quality11
considered significant in Gholipur et al.’s5 study, but not evaluated in
(Fig. 2). Two publications were overall of poor quality20,21 and the
Rothman et al.’s review, hence, other significant factors may have
remainder of intermediate quality. Most studies defined their
been overlooked in Rothman et al.’s meta-analysis. Finally, a
analysed variables and statistical analyses, however, only one
comprehensive quality assessment of methodological rigour was not
study11 conducted a proper sample size calculation. This contrib-
conducted in either review by Tang and Cuschieri6 or Rothman et al.
uted to some studies being reported as underpowered to reach
This systematic literature review aims to evaluate risk factors
statistical significance.
associated with LCeOC conversion as well as to consider the
Two studies reported missing data but failed to further describe
methodological quality of the included studies.
how these are managed in the final statistical analysis.22,23 The
missing data were also poorly described. These studies22,23 pre-
2. Methods sented the exact number of missing data but did not discuss them
further.
2.1. Protocol and registration Only one study16 was externally validated.24,25 Four studies
performed an internal validation.5,11,23,26 Gholipur et al.’s5
This systematic review was conducted according to guidelines attempted to perform an “external validation”, however, it is
set by the Preferred Reporting Items for Systematic Reviews and worth pointing out the methodology utilised was poor. Gholipur
Meta-Analysis (PRISMA).15 The review was registered in the et al. used nine cases to calculate sensitivity and specificity, with a
PROSPERO database, with the reference number CRD42016039195. point estimate of 67% and a wide confidence interval of 30%e93%,
hence making the validation insignificant. Consequently, this study
2.2. Eligibility criteria failed to meet a “low risk” for external validation of model.

Only English language full-text articles with quantitative studies 3.2. Risk factors and their association with highest possible quality
were included. Inclusion criteria for the systematic review were of the studies
studies reporting risk factors or prediction models regarding
LCeOC conversion. Retrospective and prospective studies including Several risk factors for LCeOC conversion were identified from
922 A.S.Y. Hu et al. / The American Journal of Surgery 214 (2017) 920e930

Table 1
Search strategy for PubMed.

((((“epidemiology”[MeSH Terms] OR “models, statistical”[MeSH Terms] OR “nomogram”[MeSH Terms] OR “risk factor”[MeSH Terms] OR risk* OR “risk assessment”[MeSH
Terms]))) AND ((((“Cholecystectomy”[MeSH Terms]) OR “Biliary Tract Surgical Procedures”[MeSH Terms]) OR “Cholecystectomy, Laparoscopic”[MeSH Terms])) AND
(conversion to open surgery[MeSH Terms] OR “conversion to open surgery” OR open surgery[MeSH Terms] OR conver*))

Table 2
Search strategy for Scopus.

(INDEXTERMS(“epidemiology”) OR INDEXTERMS(“models, statistical”) OR INDEXTERMS(“nomogram”) OR INDEXTERMS(“risk factor”) OR risk* OR INDEXTERMS(“risk

assessment”)) AND (INDEXTERMS(“Cholecystectomy”) OR INDEXTERMS(“Biliary Tract Surgical Procedures”) OR INDEXTERMS(“Cholecystectomy, Laparoscopic”))
AND (INDEXTERMS(“conversion to open surgery”) OR “conversion to open surgery” OR INDEXTERMS(“open surgery”) OR conver*)

the extracted studies (Table 4). Variables considered significant in
the high quality study11 were more likely to be true.
3.2.1. Variables evaluated in high quality study
3.2.1.1. Body mass index (BMI) or weight. Nineteen stud-
ies4,11,13,14,18e21,23,26e35 evaluated body mass index (BMI) or weight,
and eight of these11,13,18,20,32e35 found high BMI or high weight to
be risk factors for conversion.
3.2.1.2. Gallbladder wall thickness. Twenty studies evaluated a thick
gallbladder wall as a risk factor, with most studies using a wall
thickness of more than 4 mm as a cut-off.5,7,11,14,19,20,23,26e28,31e40
This variable was reported to increase the of conversion between
1 and 6 times in the 15 of the 20 studies which determined this risk
factor as significant.5,11,14,19,20,23,27,31,33e39
3.2.1.3. Previous history of abdominal surgery. Twenty-three stud-
ies4,5,7,11,12,14,18e20,23,26e31,34e37,39e41 evaluated having a previous
history of abdominal surgery as a risk factor, with eight of the-
se5,11,19,28e31,40 finding it significant. Seven11,19,28e31,40 of those eight
studies stated specifically that having a history of upper abdominal
surgery was significant. One of those studies30 reported that having
lower abdominal surgery was not significant while two other
studies28,29 reported that lower abdominal surgery contributed to
increased risk for conversion.
3.2.1.4. Choledocholithiasis. Of 10 studies5,7,11,18,19,23,27,35e37 evalu-
ating choledocholithiasis, five5,7,11,19,36 reported the condition to be
a significant risk factor. Four of those studies were of intermediate
quality.5,7,19,36
3.2.1.5. Impacted stone at the neck of gallbladder. One low-quality
study reported having impacted stone at the neck of the gall-
bladder as non-significant.34 However, the study of the highest
quality reported it to be significant.11
3.2.2. Variables evaluated in intermediate quality studies
3.2.2.1. Male gender. All 30 studies evaluated gender as a risk
factor.4,5,7,11e14,18,19,21,22,26e43 Male gender was considered a signif-
icant risk factor in 17 studies.4,13,18,19,21,22,26,27,31,33,34,37e41,43 Male
gender was found by Lipman et al.26 and Sanabria et al.21 to in-
crease the risk of conversion four-fold.

Table 3
Criteria for estimating risk for bias.

Low risk Intermediate risk High risk

All analysed independent variables are
defined
Sample size calculation
Data extraction procedure described
Statistical analysis described
Multivariate analysis
Missing data presented
Missing data discussed
Validation of model (internal or
external) presented
All independent variables analysed are
described/defined
Sample size calculation done AND it is
described how it was done AND The
estimated sample size (or more) was
recruited.
Medical chart or reliable database;
manually read charts or that they had
some mechanism to ensure the quality
of their database
Clearly described what is being used to
analysed data
(Multivariate stepwise
regression þ entry & removal) OR
(Multivariate non-stepwise stating
which variables were entered or if all
variables entered)
Give exact numbers of missing
data þ explain why there are more
missing data for some variables
Missing data discussed on how they
should be managed in statistical
analysis and final interpretation.
External validation of model presented
either as sensitivity and specificity OR
Area under curve (AUC).
At least 70% of all independent variables are The number of independent variables
described/defined AND the number of non- remains unclear OR less than 70% of all
described variables are stated (Hence you independent variables are clearly
know the total number of independent described/defined.
variables analysed)
Sample size calculation done AND it is No sample size calculation OR no
described how it was done AND not able to description of how it was done
recruit estimated sample size
Data extracted from a database and no No mentioning of how data is extracted
mentioning of a mechanism to ensure
quality in that database
Analysis described but not in detail Analysis not discussed
Stating multivariate regression and stating Multivariate analysis not mentioned or
if it was logistic or Cox but no more details not using multivariate regression
Give exact numbers of missing data but no Number of missing data for each
explanation for why some variables have variable not provided
more missing data
Mentions missing data in discussion but No discussion about how they managed
unclear how they managed this missing data
Internal validation of model presented Outcome of internal or external
either as (Cox&Snell R Square OR validation of their final model is not
Naegelkirke R-square) OR Area under curve described
(AUC).
 A.S.Y. Hu et al. / The American Journal of Surgery 214 (2017) 920e930
Fig. 1. Flow diagram showing identification of studies for inclusion in this systematic review according to PRISMA guidelines.
3.2.2.2. Age. Age was also evaluated by all 30 included stud-
ies.4,5,7,11e14,18,19,21,22,26e43 Older age, which was defined by most
studies as more than 60 or 65 years, was found to be an important
risk factor in 16 studies.4,7,12,13,18,20e22,27,29,30,33,35,37,39,40 One
study40 used ages of 50 years or above as a cut-off. Patients older
than 65 years had a three-fold12 or five-fold21 increased risk for
conversion.
3.2.2.3. Emergency. Five4,5,22,39,40 of nine studies4,5,7,11,13,20,22,39,40
found that emergency cases contributed significantly as a risk fac-
tor for conversion. Four out of those studies were of intermediate
quality4,5,22,40 and one of low quality.39
3.2.2.4. Acute cholecystitis. This condition was considered to be a
significant risk factor in 15 studies7,12,14,18e23,29,30,33,35,37,41 out of 20
studies evaluating its effect.7,11,12,14,18e23,26,27,29,30,33,35,37,40,41,43
These 15 studies determined the risk of conversion increased by
factor of 5 to as much as 14.7,12,14,18e23,29,30,33,35,37,41
3.2.2.5. Alkaline phosphatase. Raised alkaline phosphatase (ALP)
was reported as significant in four studies5,13,23,40 out of 15 stud-
ies4,5,7,11e14,18,19,23,26e28,35,40 in which it was evaluated.
3.2.2.6. Total bilirubin. Eleven studies4,5,7,11,14,19,26e29,35 evaluated
total bilirubin. Three of those5,7,26 found elevated bilirubin to be a
923
significant risk factor for conversion. Those studies reported bili-
rubin increased the risk up to three-fold.
3.2.2.7. White blood cell count. Seven5,13,18,23,26,27,40 of 20 studies
evaluating the effect of elevated white cell count
(WCC)4,7,11,12,14,19,26,28,29,31,35,37 determined it was significantly
associated with conversion. Six out of the seven studies were found
to have quality on par with the rest of the studies.5,13,23,26,27,40 One
study was of low quality.18 The finding of WCC effect on LCeOC
conversion was at odds with the meta-analysis conducted by
Rothman et al.,10 who claimed that there was no association.
3.2.2.8. American society of anaesthesiologist (ASA) score. ASA
scores were assessed in 11 studies.4,11e13,22,23,26e28,35,38 However,
only one study of intermediate quality found that having an ASA
score of more than 3 was significantly correlated to conversion.22
4. Other risk factors
Elevated body temperature was considered a significant risk
factor for conversion in one study.5 Kaafarani et al.4 found that
hypertension, hyponatremia, a haematocrit level less than or equal
to 38%, and increased international normalised ratio (INR) were all
significant factors.
One study reported significant risk of conversion where
924 A.S.Y. Hu et al. / The American Journal of Surgery 214 (2017) 920e930

Fig. 2. Quality assessments of included studies. (Color version of figure available online.)
 A.S.Y. Hu et al. / The American Journal of Surgery 214 (2017) 920e930 925

Table 4
Characteristics of included studies with statistically significant variables.

Author, Year Country Sample size Prediction variables P value Odds ratio AUC

Goonawardena, 2015 Total: 732 Previous upper abdominal surgery 0.0041 95 (4.2e2200) 0.97
Australia11 Start as lap: 732 Obesity/BMI > 30 > 27.2 kg/m2 0.00011 12 (3.5e44)
Converted: 47 Ultrasonographic measures
Start as open: 0 Choledocholithiasis 0.00013 20 (4.3e91)
Gallbladder wall width (mm) (no specific cut-offs) <0.000001 2.1 (1.6e2.6)
Impacted stone at neck of gallbladder 0.0053 5.9 (1.7e20)
Sippey, 2015 Total: 7242 Age >60 years 0.015 1.01
USA13 Start as lap: 7242 Male 0.005 1.77
Converted: 436 BMI > 30 kg/m2 0.0001 1.04
Start as open: 0 Preoperative ALP 0.0005 1.01
WCC (no specific cut-offs) 0.0001 1.06
Albumin (no specific cut-offs) 0.0001 0.52
Licciardello, 2014 Total: 414 Acute cholecystitis 0.001 5.6 (2.1e15)
Italy12 Start as lap: 414 Age  65 years 0.036 3.0 (1.1e8.5)
Converted: 33
Start as open: 0
Stanisic, 2014 Total: 369 Previous episodes of acute cholecystitis 0.000
Montrego14 Start as lap: 369 Thickened GB wall >4 mm 0.000
Converted: 10 Acute cholecystitis to admission 0.000
Start as open: 0 Gallstones size >2 cm 0.000
Recurrent pain >4 h in >5 episodes 0.001
Diabetes mellitus 0.000
Duration of disease >36months 0.004
Pericholecystic fluid 0.021

Cwik, 2013 Total: 5596 BMI > 25e30 kg/m2 <0.05
Poland32 Start as lap: 4105 Delay of surgery >72 h from time of admission w <0.05
Converted: 130 concomitant acute symptoms of inflammation
Start as open: 1491
Sultan, 2013 Total: 4698 Male <0.001 2.79 (1.97e3.97)
Egypt40 Start as lap: 4434 Age > 50 years <0.001 0.502 (0.351e0.719)
Converted: 234 Previous upper abdominal surgery <0.001 0.228 (0.105e0.497)
Start as open: 264 ALP <0.001 1.21 (1.15e1.27)
WCC > 9  10^3/ul <0.001 0.303 (0.165e0.558)
Urgently indicated pt/emergency <0.001 0.095 (0.060e0.151)
O'Leary, 2013 Total: 1061 Male 0.015
Ireland38 Start as lap: 1061 Thickened gallbladder wall > 4 mm 0.019
Converted: 58 Contracted gallbladder 0.037
Start as open: 0
Raman, 2012 Total: 874 Age (no specific cut-offs) 0.016 1.0 (1.0e1.0)
USA39 Start as lap: 874 Male <0.001 3.0 (1.7e5.3)
Converted: 68 Diabetes Mellitus 0.008 2.4 (1.3e4.5)
Start as open: 0 Emergent cholecystectomy 0.003 2.9 (1.5e5.8)
Emergent: 549 Thickened gallbladder wall (no specific cut-offs) 0.002 1.2 (1.1e1.3)
Elective: 325
Yajima, 2012 Total: 407 Male 0.047 2.0 (1.1e3.6)
Japan41 Start as lap: 407 Acute cholecystitis <0.001 8.5 (2.4e30)
Converted: 47
Start as open: 0
Kanakala, 2011 Total: 2197 Male 0.005 1.68 (1.17e2.40)
UK22 Start as lap: 2117 ASA III 0.012 2.01 (1.16e3.47)
Converted: 133 ASA IV 0.022 4.70 (1.26e17.6)
Start as open: 80 Emergency 0.005 1.75 (1.19e2.57)
Elective LC: 1706 Laparoscopic Cholecystectomy þ common bile duct 0.001 2.74 (1.52e4.94)
exploration
van der Steeg, 2011 Total: 972 Age >65 years <0.05 2.1 (1.3e3.3)
Netherlands43 Start as lap: 972 Male <0.05 1.7 (1.1e2.6)
Converted: 121 Acute cholecystitis <0.05 12 (7.0e20)
Start as open: 0 Recent acute cholecystitis <0.05 4.7 (2.4e9.2)
Recent obstructive jaundice <0.05 21 (4.5e94)
Domíguez, 2011 Total: 703 Male 0.023 1.7 (1.1e2.8)
Colombia27 Start as lap: 703 Age >70 years 0.001 2.7 (1.6e5.0)
Converted: 97 Raised WCC (>12,000 mm3) 0.04 1.6 (1.0e2.7)
Start as open: History of ERCP 0.05 2.0 (0.50e4.5)
Thickened gallbladder wall  7 mm 0.072 1.6 (0.96e2.5)
Kaafarani, 2010 Total: 11,669 Emergent procedure 0.0091 1.42 (1.09e1.84)
USA4 Start as lap: 9530 Male 0.0001 2.40 (1.73e3.33)
Converted: 949 History of previous surgery <0.0024 1.64 (1.20e2.25)
Start as open: 1189 Hypertension 0.0244 1.21 (1.03e1.43)
Hematocrit  38% 0.006 1.27 (1.07e1.51)
Na  135 mEq/L 0.0001 1.47 (1.22e1.79)
WCC > 11,000 mm3 <0.0001 2.10 (1.75e2.52)
Age (no specific cut-offs) 0.0001 1.01 (1.01e1.02)
INR (þ1U) <0.0001 2.29 (1.58e3.33)
(continued on next page)
926 A.S.Y. Hu et al. / The American Journal of Surgery 214 (2017) 920e930

Table 4 (continued )

Author, Year Country Sample size Prediction variables P value Odds ratio AUC

Serum albumin (1 g/dL) <0.0001 1.43 (1.26e1.62)

Hospital-specific conversion rate <0.0001 1.11 (1.10e1.12)
Ercan, 2010 Total: 2963 Previous upper abdominal incision 0.015 3.40 (1.13e9.05)
Turkey28 Start as lap: 2963 Previous upper & lower abdominal incision 0.015 4.53 (1.35e15.9)
Converted: 101 Preoperative ERCP 0.004 1.84 (1.21e2.79)
Start as open:0 Gallbladder adhesion score (Grade 4) 0.0001 4.76 (3.32e6.83)
Gallbladder appearance (scleroatrophic) 0.0001 5.60 (2.46e12.7)
Gholipour, 2009 Total: 793 Experience 0.013 2.3 (1.2e4.4)
Iran5 Start as lap: 793 Emergency surgery 0.020 0.44 (0.22e0.88)
Converted: 9 Previous history of laparotomy 0.045 1.7 (1.0e2.9)
Start as open: 0 Choledocholithiasis 0.011 6.9 (1.6e3.1)
Thickened gallbladder wall (no specific cut-offs) 0.053 1.8 (0.99e3.2)
Body temperature (no specific cut-offs) 0.022 1.9 (1.1e3.4)
Elevated WCC (no specific cut-offs) 0.0051 1.0 (1.0e1.0)
Bilirubin (no specific cut-offs) 0.044 0.65 (0.43e0.99)
ALP (no specific cut-offs) 0.0012 1.0 (1.0e1.0)
Zhang, 2008 Total: 1265 History of previous upper abdominal surgery <0.05 6.13 (3.33e11.3)
China31 Start as lap: 1265 Gallbladder wall thickness > 4 mm <0.05 4.12 (2.61e6.50)
Converted: 94 Murphy's sign <0.05 2.71 (1.72e4.28)
Start as open: 0 Male <0.05 1.92 (1.22e3.03)
Lipman, 2007 Total: 1377 Male <0.05 4.06 (2.42e6.82) 0.83
USA26 Start as lap: 1377 Elevated WBC <0.05 3.01 (1.77e5.13)
Converted: 112 Low albumin <0.05 2.90 (1.70e4.96)
Start as open: 0 Pericholecystic fluid on USS <0.05 2.36 (1.25e4.47)
Diabetes mellitus <0.05 1.87 (1.03e3.42)
Elevated total bilirubin <0.05 1.85 (1.01e3.39)
Ischizaki, 2006 Total:1339 >4 mm gallbladder wall on USS <0.001 9.26 (5.54e15.5)
Japan36 Start as lap: 1179 History of common bile duct stone removed by ES <0.001 5.75 (3.03e10.9)
Converted: 89 (endoscopic sphincterotomy)
Start as open: 160
Ibrahim, 2006 Total: 1000 Age > 60 years 0.004 2.2 (1.3e3.9)
Singapore18 Start as lap: 1000 Weight > 65 kg 0.029 1.8 (1.1e2.9)
Converted: 103 Male 0.031 1.3 (1.0e2.0)
Start as open: 0 Acute cholecystitis 0.003 1.6 (1.2e2.0)
Precious upper abdominal surgery 0.04 1.1 (0.98e1.8)
Total WCC (>10  10^3 U/I) 0.014 0.78 (0.43e1.0)
Experience/operated by junior surgeon 0.04 1.3 (0.99e1.8)
HbA1c level (>6) (for DM patients) 0.05 1.2 (0.98e1.9)
Presence of chronic lung disease 0.058 0.85 (0.50e1.5)
Simopoulous, 2005 Total: 1804 Age  61 years <0.001 5.73 (2.40e13.67)
Greece29 Start as lap: 1804 Inflammation <0.001 7.07 (4.47e11.14)
Converted: 94 History of lower abdominal surgery 0.027 0.50 (0.27e0.92)
Start as open: 0 History of upper abdominal surgery 0.002 3.85 (1.64e9.04)
Mirza, 2003 Total: 2541 Age  65 years 0.0114
Saudi Arabia37 Start as lap: 2541 Male 0.0001
Converted: 94 Raised WCC 0.0041
Start as open: 0 Past history of acute cholecystitis 0.00001
Acute cholecystitis 0.00001
Gallbladder wall thickness 0.00001
Previous history of abdominal operation 0.00001
Rosen, 2002 Total: 1347 Acute cholecystitis 0.02 2.76 (1.20e6.36)
USA35 Start as lap: 1347 Age (no specific cut-offs) 0.002 1.22 (1.07e1.38)
Converted: 71 BMI > 30 kg/m2 0.0008 1.53 (1.19e1.97)
Start as open: 0 Thickened gallbladder wall >4 mm on USS 0.004 1.47 (1.13e1.92)
Kama, 2001 Total: 1000 Male <0.05 0.83
Turkey19 Start as lap: 1000 Previous abdominal surgery <0.05
Converted: 48 Acute cholecystitis <0.05
Start as open: 0 Thickened gallbladder on USS <0.05
Suspicion on CBD stones <0.05
Alponat, 1997 Total: 783 Acute cholecystitis 0.0033 3.1 (1.5e6.7)
Singapore23 Start as lap: 783 Elevated ALP (no specific cut-offs) 0.019 2.2(1.1e4.4)
Converted: 58 Elevated WCC (>11,000 mm3) 0.0006 3.7 (1.8e7.8)
Start as open: 0 Thickened gallbladder wall on ultrasound  3.5 mm 0.0003 3.8 (1.8e7.7)
Liu, 1996 Total: 500 Age > 65 years <0.05
Hong Kong20 Start as lap: 500 Obesity <0.05
Converted: 45 Acute cholecystitis <0.05
Start as open: 0 Thickened gallbladder on USS <0.05
Patient seen during early learning phase <0.05
Wiebke, 1995 Total: 581 Age > 50 years 0.022 1.0
USA30 Start as lap: 581 Veteran patients 0.0010 3.7
Converted: 45 Acute cholecystitis 0.0003 4.6
Start as open: 0 Upper abdominal surgery 0.0002 5.2
Fried, 1994 Total: 1676 Acute cholecystitis <0.05 5.79 (3.21e10.4)
Canada33 Start as lap: 1676 Age  65 years <0.05 2.00 (1.15e3.49)
Obesity (no specific cut-offs) <0.05 1.77 (1.02e3.05)
 A.S.Y. Hu et al. / The American Journal of Surgery 214 (2017) 920e930 927

Table 4 (continued )

Author, Year Country Sample size Prediction variables P value Odds ratio AUC

Converted: 90 Male <0.05 2.54 (1.48e4.37)

Start as open:0 Thickened gallbladder wall (no specific cut-offs) <0.05 1.72 (0.93e3.20)
Sanabaria, 1994 Total: 628 Age >65 years <0.01 5.0 (1.5e16)
USA21 Start as lap: 628 Male <0.01 4.0 (1.8e9.1)
Converted: 32 Number of LC procedures, <50 v >50 <0.05 3.8 (1.3e11)
Start as open: 0 10 biliary colic <0.01 7.0 (2.2e22)
Acute cholecystitis <0.01 12 (4.6e56)
Hutchinson, 1994 Total: 526 Male <0.02 2.6 (1.2e5.4)
USA34 Start as lap: 526 BMI > 27.2 kg/m2 <0.01 1.8 (1.4e5.7)
Converted: 45 Ultrasonographic measures
Start as open: 0 Thickened gallbladder wall (no specific cut-offs) <0.001 6.0 (2.5e14)
Intraoperative data
Positive cholangiogram <0.02 4.2 (1.4e13)
Risk of positive cholangiogram common bile duct (CBD) <0.001 6.8 (2.4e19)
dilatation on preoperative ultrasound (USS)
Peters, 1994 Total: 746 Acute cholecystitis <0.05 14 (8e27)
USA7 Start as lap: 746 Suspected CBD stone <0.05 11 (4.1e30)
Converted: 101 Total bilirubin <0.05 2.6 (1.3e4.9)
Start as open: 0 Age > 60 years <0.05 2.3 (1.1e5.1)

procedures were conducted by surgeons with less experience in
laparoscopic cholecystectomy.5 This factor was also supported by
another low quality study.18
Two studies evaluated having a history of endoscopic retrograde
cholangio-pancreatography (ERCP), with both finding the factor to
be significant.27,28
One study reported having a delay of surgery of more than 72 h
from time of admission with concomitant acute symptoms of
inflammation to be significant.32
Three14,26,39 out of four studies that evaluated diabetes mellitus
reported this factor to be significant in the risk of conversion.
4.1. Variables evaluated in low quality studies
Variables considered to be significant and found only in low
quality studies included a positive result for Murphy's sign,31 a
HbA1c level of more than 6 in a diabetic patient, and chronic lung
disease,18 gallbladder adhesions, and scleroatrophic gallbladder.28
4.2. Risk score and predictive models
Various scoring or predictive models have been proposed for
probability for conversion.11,19,23,44 Kama et al.16 proposed the risk
score for conversion from laparoscopic to open cholecystectomy
(RSCLO). The score included variables such as male gender,
abdominal tenderness, previous upper abdominal surgery, a
thickened gallbladder wall, age above 60 years, and the presence of
acute cholecystitis.
An equation to predict conversion was developed by Lipman
et al.26 based on statistically significant factors, namely male sex,
low serum albumin, elevated WCC, pericholecystic fluid on ultra-
sound, diabetes mellitus, and elevated total bilirubin. An area under
the curve (AUC) of 0.83 was demonstrated in both the Kama and the
Lipman models.16,26
Kama et al.’s16 model was externally validated by Bulbuller
et al.24 and Kologlu et al.25 and both studies showed high sensitivity
and specificity for the scoring system. Bulbuller et al.24 reported
sensitivity and specificity rates for RSCLO determining the risk of
conversion as being 100% and 96%, respectively, and its positive and
negative predictive values were 43% and 100%, respectively.
It is also worth noting that RSCLO by Kama et al.’s16 prediction
method (16) was developed with significantly fewer variables,
including a notable lack of radiological factors in the analysis,
compared to the model by Goonawardena et al.11 and Alponat
et al.23
Goonawardena et al.11 developed a prediction model graphically
illustrated by four probability nomograms to predict conversion.
Statistically significant variablesdprevious upper abdominal sur-
gery, obesity, choledocholithiasis, thickened gallbladder wall and
impacted stone at the neck of the gallbladderdwere used in the
model. AUC of 0.97 was demonstrated as an internal validation of
the model.
Alponat et al.23 developed a formula with four parameter-
sdacute cholecystitis, elevated ALP, elevated WCC and thickened
gallbladder wall on ultrasound. To the best of our knowledge, this
formula has not been externally validated.
The pattern that could be observed from these risk scores or
models is that the risk of conversion increased when more risk
factors were present. As reported by Alponat et al.’s23 model, a 59%
conversion rate was observed when all four predictors were pre-
sent as compared to 1.5% when none of the predictors were present.
The same trend can be observed in Goonawardena et al.’s11 study.
5. Discussion
A total of 30 studies involving data on 57,303 patients were
included in this systematic review. This review endorses a credible
association between some frequently reported risk factorsdsuch as
male sex, older age, high BMI, the presence of acute chol-
ecystitisdand conversion of laparoscopic to open cholecystectomy.
The prevalence of gallstone disease is between two to three
times more common in women than in men.45 However, the risk of
conversion appeared notably higher in men, a trend also observed
across all different types of surgery.46 The most common cause of
conversion is difficult dissection of Calot's triangle during LC. One
study demonstrated that symptomatic gallbladder stones, inflam-
mation, and fibrosis were more extensive in men than in women,
which may explain the higher rate of conversion in male patients.47
A study reported that the conversion rate for elderly patients
was 15% as compared to only 8% in their younger patients.48 It has
been postulated that a longer history of cholelithiasis, and an
increased number of cholecystitis attacks (or chronic cholecystitis)
may have contributed to higher rates of conversion.29 Similarly, in
acute cholecystitis dissection can be challenging due to a thickened
and friable gallbladder wall and dense scarring. The cystic duct may
become foreshortened and the gallbladder densely adherent to the
common bile duct.33 Bleeding hindering the view of Calot's triangle
may impose the need for conversion. However, multiple studies
argued that LC was still feasible and effective, provided a more
careful selection of patients was performed.49,50
928 A.S.Y. Hu et al. / The American Journal of Surgery 214 (2017) 920e930
Obesity had been reported to contribute to conversion. This may
be due to a variety of reasons, such as inadequacy of trocar length,
port misplacement, and heavy infiltration of fat in Calot's triangle
obscuring critical anatomy.20,33,35
5.1. Unconventional findings and significance
An impacted stone in the gallbladder neck was reported to be
significant enough to be included in the development of a nomo-
gram.11 This variable may be associated with Mirizzi's syndrome,
which often presents itself with dense adhesions and oedematous
inflammatory tissue in Calot's triangle, necessitating meticulous
dissection to avoid bile duct injury.51 This variable has been sug-
gested as a high-risk factor for conversion.52,53
The study also reported a history of previous upper abdominal
surgery carried the highest odds ratio of 95 for a significant con-
version risk factor. Prior surgery may cause adhesions and adher-
ence of the duodenum to the liver, omentum and anterior
abdominal wall rendering Calot's triangle inaccessible.54
Modifiable risk factors such as smoking and drinking, were also
reported to be significant in Gholipur et al.’s study.5 In a sono-
graphic study, it was shown that maximal gallbladder emptying
time was prolonged with smoking. Its effect was mostly observed in
the acute phase resulting in bile stasis, which is the underlying
aetiology of most gallbladder disorders in a chronic process.55
This current review found several conversion factors that were
not investigated by many studies, including body temperature,
comorbidities such as diabetes mellitus or hypertension, delays
before surgery of more than 72 h from time of admission with acute
cholecystitis, and surgeons having lesser experience in laparoscopic
cholecystectomy. Studies that did find these factors significant were
of intermediate quality. Hence, more evidence from high quality
studies is warranted.
Two studies included factors relating to armed forces veterans.
One study of intermediate quality30 found being a veteran was a
risk factor, while another study of intermediate to high quality4 also
reported a higher hospital-specific conversion rate as significant in
data collected from a veteran's hospital. More evidence from high
quality studies investigating veteran status is therefore justified.
5.2. Prediction models
Open surgeries have several advantages over laparoscopy
particularly in difficult situations. Surgeons can apply manual
pressure, experience better tactile feedback, have better exposure
and movements, and there is less restriction on the number of
instruments.56
Identifying patients with significant risk factors for conversion
could minimise the adverse effects of prolonged surgery by limiting
the duration of the trial of laparoscopic dissection.23,57,58 Low risk
patients could also be safely operated on in day surgery facilities.16
The effective use of prediction models will enable hospitals to plan
and allocate resources more appropriately, especially as extra care
and services to prevent or treat complications may be needed in
high-risk patients.59 Surgical residents operating without the su-
pervision of an experienced surgeon need to identify low-risk pa-
tients, which can be achieved through appropriate use of these
models. Appropriate training under supervision can also be plan-
ned for residents requiring training in high-risk cases or in open
surgery.16,21,33
This systematic review found several useful prediction models
which might be utilised by surgeons to select cases where direct OC
may be the best option. The overall usefulness of these models are
usually evaluated with estimates such as Nagelkerke R-square,
sensitivity and specificity, predictive values, and AUC. Sensitivity,
specificity and predictive values assume a fixed cut-off for all sce-
narios. AUC is a more practical measure because hospitals and in-
stitutions can decide their own cut-off score by taking different
factors, e.g. patient demographics, hospital resources, surgeon's
experience and other local conditions into consideration to opti-
mise patient safety.
The clear graphical nomogram developed by Goonawardena
et al.11 may be the most practically useful tool for hospitals to
determine their own risk cut-off. It was also the prediction model
with the highest accuracy to date, with a near perfect receiver
operating characteristic, with an AUC of 0.97. An external validation
of this prediction model is therefore warranted.
Furthermore, from a patient's standpoint, these models will
enable prediction of operation type, and thus reasonable planning
of time needed off work, childcare and family. Informed decisions
can be made with proper education on the likelihood or otherwise
of conversion based on the risk models.60
6. Strength of this review
Compared to the previous reviews,6,10 this review has a strong
focus on the methodological quality of included publications. To the
best of our abilities, an appropriate quality assessment criteria
catering specifically to this literature review could not be identified.
Hence, a novel and a suitable set of methodological quality criteria
were developed. All the included studies underwent rigorous as-
sessments of their methodological quality, and the compilation of
extracted risk factors was influenced by the quality of evidence
demonstrated in those studies. Only studies with more than 300
patients and those which underwent multivariate analysis were
chosen to further improve quality. Furthermore, this review iden-
tified significant novel risk factors not reported in previous reviews,
such as impacted stone at the gallbladder neck, which was not
reported in previous reviews. As an extension of only including
studies utilizing a multivariate statistical analysis, this review also
analysed prediction models more thoroughly, including the as-
sessments of their accuracy and utility.
7. Limitation of this review
This review only included English language studies. Studies
published in other languages may exist and were not identified.
One paper was not available in full-text61 despite attempts to
retrieve the article by contacting the author and managing editor of
the journal. Owing to the heterogeneity of the studies reviewed, a
meta-analysis was not performed.
8. Conclusion
The studies in this review have reported numerous significant
risk factors associated with conversion. However, only one study
was determined to be of high methodological quality.
The use of prediction risk scores or nomograms may be the most
helpful tool in stratifying risks in a clinical scenario. Through such
prediction tools, clinicians can optimise care based on the known
risk factors for conversion, while patients can be better informed of
the risks associated with their surgery.
Conflicts of interest
Alan de Costa and Ronny Gunnarsson are co-authors on one of
the publications included in this review.
 A.S.Y. Hu et al. / The American Journal of Surgery 214 (2017) 920e930
Acknowledgements
We thank the librarians of Cairns Hospital Library and Knowl-
edge Centre, Thomas Ang and Katherine Streitch for helping to
develop the search strategy and retrieve some articles. We also
thank Tyler Chin and Grace Cham for reviewing the manuscript.
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