MESTRADO INTEGRADO EM MEDICINA

Iatrogenic bile duct injuries in the era of laparoscopic cholecystectomy

Ana Margarida Ferreira Maia Gomes Cabral

M 2018

     

ARTIGO DE REVISÃO BIBLIOGRÁFICA

 IATROGENIC BILE DUCT INJURIES IN THE ERA OF

LAPAROSCOPIC CHOLECYSTECTOMY

Dissertação de candidatura ao grau de Mestre em Medicina submetida ao Instituto de Ciências Biomédicas Abel Salazar da Universidade do Porto

Orientadora Mestre Donzília da Conceição Sousa da Silva Assistente Graduada de Cirurgia Geral da Unidade Hepato-biliar e Pancreática do Centro Hospitalar do Porto Professora Auxiliar Convidada do Instituto de Ciências Biomédicas Abel Salazar da Universidade do Porto Autora Ana Margarida Ferreira Maia Gomes Cabral mim11119@icbas.up.pt Maio de 2018

  i  

Resumo

Contexto: As lesões das vias biliares são um problema relevante na colecistectomia

laparoscópica, com um grande número de publicações dedicadas a este tema. Apesar de

todas as vantagens da abordagem laparoscópica, este procedimento ainda é marcado

pelo receio de lesão iatrogénica das vias biliares. Esta revisão pretende reunir o

conhecimento atual sobre esta matéria.

Métodos: Revisão de literatura sobre lesões das vias biliares em colecistectomias

laparoscópicas para analisar a sua incidência, classificação, demografia, causas e fatores

de risco, tratamento, mortalidade e uso de colangiografia intra-operatória. Grandes séries

(>1000 colecistectomias laparoscópicas) foram obtidas através de uma pesquisa na

PubMed. Outras referências foram encontradas a partir de artigos relevantes.

Resultados: foram encontradas 14 séries com mais de 1000 doentes que abordavam

lesões das vias biliares durante colecistectomias laparoscópicas, tratando o tema de

perspetivas diferentes.

Conclusão: a colecistectomia laparoscópica é uma cirurgia segura, mas os cirurgiões

devem ter em conta a possibilidade de lesão iatrogénica das vias biliares a qualquer

momento. A sua incidência é maior do que a incidência em colecistectomias por

laparotomia, mas a maioria das lesões não é complexa e pode ser tratada com sucesso.

Deve haver uma avaliação de fatores de risco antes da cirurgia para todos os doentes.

Os cirurgiões devem identificar as estruturas anatómicas com precisão. A colangiografia

intra-operatória é importante em certos casos, e os cirurgiões hepato-biliares são

essenciais no tratamento de lesões das vias biliares.

  ii  

Abstract

Background: Bile duct injury is a relevant problem in laparoscopic cholecystectomy, and a

gross body of literature has been dedicated to this topic. Despite all of the advantages of

the laparoscopic approach, this procedure is still marked by the fear of iatrogenic bile duct

injury. This review aims to be a state of the art on the subject.

Methods: Review of literature concerning bile duct injuries during laparoscopic

cholecystectomy to address its incidence, classification, demographics, causes and risk

factors, management, mortality and use of intraoperative cholangiography. Large series

(>1000 laparoscopic cholecystectomies) were extracted from a search through PubMed.

Other relevant references were obtained from main articles.

Results: 14 series with more than 1000 patients assessing bile duct injury during

laparoscopic cholecystectomy were found, each one addressing the injuries in a different

way.

Conclusion: Laparoscopic cholecystectomy is a safe procedure, but surgeons should keep

in mind the possibility of bile duct injury at any time. Incidence is higher than that of open

cholecystectomy, but most injuries are not complex and can be managed with success.

There should be a preoperative evaluation of risk factors for every patient. Surgeons must

recognize biliary anatomy accurately. Intraoperative cholangiography is important in

selected cases, and hepatobiliary surgeons are essential in the management of bile duct

injuries.

  iii  

List of abbreviations

BDI Bile Duct Injury

CT Computed Tomography

EAES The European Association of Endoscopic Surgery

ERCP Endoscopic Retrograde Cholangiopancreatography

ESGE European Society of Gastrointestinal Endoscopy

IOC Intraoperative Cholecystectomy

LC Laparoscopic Cholecystectomy

LUS Laparoscopic Ultrasonography

MRCP Magnetic Resonance Cholangiopancreatography

NBD Nasobiliary Drain

NIS Nationwide Inpatient Sample

OC Open Cholecystectomy

PRISMA Preferred Reporting Items for Systematic Reviews and Meta-

Analysis

PTC Percutaneous Transhepatic Cholangiography

RHA Right Hepatic Artery

US Ultrasound

  iv  

Index

Introduction 1

Methods 1

Results 2

Discussion 6

Figures 19

Tables 20

List of references 21

  1  

Introduction

The introduction of laparoscopic cholecystectomy (LC) more than 3 decades ago1

changed the way cholecystectomy is performed. This procedure started being increasingly

performed in the years that followed2 and it is now the standard method when removing

the gallbladder, having replaced traditional open cholecystectomy (OC). However, this

technique has been associated with an increase in the incidence of iatrogenic injuries to

the biliary tree.3

The rate of bile duct injury (BDI) was reported to be higher in the years following

the introduction of LC.4 This was proposed to be due a "learning curve" effect4, therefore,

it was expected to lower down as surgeons would get more experienced with the new

procedure.3 By that time, the rate was reported to be higher than the rate of BDI after

open cholecystectomy.5–8 Yet, some studies support that this rate remained higher.3,8–10

Stated by some as the most important cause of morbidity11, BDI after LC can be a

serious complication1, which may require complex management and have an effect on the

patient's quality of life.4 This review aims to review the incidence, classification,

demographics, causes and risk factors, management and results of BDI after LC.

Methods

Protocol

This systematic review was conducted following the guidelines set by the

Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA).

Elegibility criteria

Only full-text articles were included, published in English, Portuguese and Spanish

language. No restrictions were made regarding the time of publication.

Inclusion criteria for the systematic review were studies based on series of more

than 1000 patients who underwent elective or emergency laparoscopic cholecystectomies

reporting BDI incidence and other characteristics of BDIs, such as demographics, risk

factors, and management. Case reports were disregarded. Studies including observations

from both laparoscopic and open cholecystectomies were included, after ensuring each

procedure had its own separate data.

  2  

Search strategy

Two different searches were performed through PubMed on 8 February, 2018. The

key words "iatrogenic bile duct injury laparoscopic cholecystectomy" and "medical errors

bile duct injuries laparoscopic cholecystectomy" were used in order to identify the most

recent and the best matched articles published in literature, respectively. After screening

through publication titles and abstracts, full-text articles were reviewed according to the

inclusion criteria. Other relevant articles were found through reference lists of main

articles.

Results

The preliminary searches found 177 full-text papers potentially significant for this

review (figure 1). Additional records were identified through studies' reference lists (n=75).

After exclusion of replicates (n=4), non-English, -Portuguese or -Spanish papers (n=13),

studies not related to LC (n=9) and studies concerning species other than humans (n=2)

were excluded. 224 titles and abstracts were then assessed for eligibility, and there was

an exclusion of articles that did not share relevant information (n=83), were cases reports

(n=28) or were related to other species (n=4). It was not possible to access 1 study. The

inclusion criteria were applied to select studies in order to present and discuss big series

reporting LCs and BDIs. 18 articles were pertinent for this purpose, but some were based

on less than 1000 patients (n=4); therefore, according to the inclusion criteria, the results

of 4 studies were not presented and discussed. The other studies, which were not

excluded, were used as a basis to gain insight into the discussed topics and for review

purposes. In total, 107 studies were cited.

One prospective study by Richardson et al12 was based on 5913 LCs performed

from 1990 until 1995. From this group, information about 101 LCs is missing, but the

98,3% completed data was independently validated by 1 research nurse. A study by Veen

et al13 based on data collected prospectively from 1998 to 2006 reported 1254 LCs,

including 13 BDIs. The data extraction was described and additionally two not affiliated

authors evaluated all patient files for non-registered complications, and found another 2

cases of BDI.

A study by Grönroos et al14, based on 3736 LCs performed in a single institution

from 1995 to 2002, was conducted to identify if male gender was associated with BDI. It

did not describe the data extraction process but found 32 BDIs. A study by Karvonen et

al15 was based on the same database during the same period of time, therefore had the

  3  

same results and will not be discussed. Yet, the authors shared further data on mortality

and management of the patients, which will be included.

A retrospective study by Fullum et al16 analyzed a nationwide database, the

Nationwide Inpatient Sample (NIS), to find patients who underwent cholecystectomies (LC

and OC) from 1998 to 2006. The aim was to find patient and hospital factors potentially

associated with BDI. The factors were examined by use of bivariate and multivariate

analysis and included, among others, age, race, gender, morbid obesity, diagnosis of

acute cholecystitis, intraoperative cholangiography, year of procedure and hospital annual

volume of cholecystectomies. They found 177 BDIs in a total of 312522 LCs. Another

retrospective study, by Aziz et al,17, which had the same goal, used records from the

same database, but analyzed data from 2010 until 2012 concerning 39844 LCs, and

found 177 BDIs. Univariate and multivariate analysis were perfomed to find association

between the same factors and BDI. One study was based on the same database on the

same period of time as the one by Fullum et al16, therefore it is not discussed, as it would

be a replica.

A retrospective multicenter study by Savassi-Rocha et al18 described 91232 LCs

performed from 1990 until 1997. It found 167 BDIs and a further 83 cystic duct injuries

which were not included in the analysis. Another retrospective single institution study by

Tantia et al19 was based on data recorded for 13 consecutive years, from 1992 to 2005.

A retrospective study by Demartines et al1 reported BDI after LC based on data

from 11 year experience, from 2000 until 2011, from a single-institution.

A multicenter retrospective by Malik et al20 analyzed 1132 LCs performed from

2003 to 2007 and found 19 BDIs, plus 13 minor postoperative bile leaks which resolved

spontaneously and were not included in the analysis.

A multicenter retrospective study by Hamad et al21 extracted data from patients

undergoing LC between 2004 and 2009, selecting only cases where IOC had not been

used, thus excluding the ones where surgeons had resorted to this procedure (a "no-

intraoperative cholangiography policy"). There is a concern that this lead to a selection

bias, where mostly not so complex LCs, that did not require cholangiography at the time

they were performed, would be included. Therefore, their results are not included in this

review. A survey by Paczyński et al22 analyzed 6873 patients who underwent LC from

1991 until 2000. It did not describe how data was extracted or discuss its own results.

Hence, this survey is not presented in this review. A study by Suliman and Palade23

reported 1402 LCs in patients suffering from acute cholecystitis. It addresses mostly

problems encountered in this disease and does not provide the information needed for

this review, therefore their results are not discussed.

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Incidence of BDI

All of the studies reported the incidence of BDI caused by LC. The rate was found

to range between 0,06%16 and 2,55%17.

Among the earlier series, Richardson et al12 and Savassi-Rocha et al18 (1990-1995

and 1990-1997) reported an incidence of 0,63% and 0,18%, respectively. Grönroos et al14

(1995-2002) reported an increase of the rate up to 0,86%. Concerning the first half of the

2000s (1998-2006), Veen et al13 and Fullum et al16 stated that the incidence was 1,20%

and 0,06%, respectively. From 2003 to 2007, Malik et al20 reported a rate of 1,68%. The

highest value was found in the most recent study (2010-2012), by Aziz et al17, which

reported a rate of BDI of 2,55%.

Tantia et al19 and Demartines et al1, based on data from 13 and 11 consecutive

years from single institutions (1992-2005 and 2000-2011), reported a rate of 0,39% and

0,46%, respectively.

Classification of BDI

Only two studies used the Strasberg-Bismuth classification. Tantia et al19 reported

that the most frequent injuries were Strasberg type A and type D (27 and 14 out of 52

BDIs). When these were excluded, most of the BDIs occurred in the middle CHD and

identified as E (2 E1, 3 E2 and 1 E3 injuries). 32 were identified intraoperatively.19

Demartines et al1 reported that, out of 13 BDIs, the most frequent injuries were Strasberg

type A, 4, and D, also 4, followed by E1, 3, and E5, 2. 6 injuries were identified

intraoperatively.

Veen et al13 used the Strasberg classification. Out of 13 injuries, 8 classified as

Strasberg type A, 4 as type D and 1 as type E. The study also reported 1 additional bile

leak from the cystic duct and 1 lateral injury of the common bile duct.

Savassi-Rocha et al18 applied the Bismuth classification to 158 out of the 167

BDIs. The most frequent were type 1 injuries, 107, followed by 41 type 2 lesions, 9 type 3

and 1 type 4 injury. The other 9 BDIs were reported to be isolated injuries of the right

hepatic duct. 113 injuries were discovered during the procedure. They also reported 83

cystic duct injuries.

Grönroos et al14 used the Amsterdam Criteria. They report 10 type A, 5 type B, 8

type C and 9 type D injuries. Other 2 studies used different systems and 2 did not specify

the types of BDI suffered by the patients.

Richardson et al12 used the McMahon classification and considered 20 injuries as

major, which included 9 lacerations of the CBD, 8 injuries of the CHD including significant

trauma to the confluence, 1 right hepatic ductal laceration and 2 strictures at the cystic

duct insertion. The other 17 were considered minor and comprised 9 small lacerations in

  5  

the CBD, 6 lacerations of the CHD and 2 of the RHD. From the 37 injuries, 18 were

detected during the procedure while 19 were found in the postoperative period.

Malik et al20 comprised 3 transections of aberrant RHD, 7 partial injuries to major

biliary ducts, 5 accidental holes in CBD, 1 CBD mistakenly clipped and not recognized, 1

CBD clipped in place of cystic duct but recognized immediately and 2 accidental holes in

the CHD. 7 injuries were identified intraoperatively.

No studies mention concomitant vascular injuries.

Patient gender

Only 4 studies1,14,17,19 mention the gender of patients who sustained BDI.

Demartines et al1 reports 7 BDIs occurred in females and 6 in males. On another

two studies14,19, BDIs occurred mostly in females (25 vs. 7 males14 and 32 vs. 20 males19).

However, in one of these studies the authors concluded male gender seemed to be

associated with BDI19 and the other found no statistically difference in the risk of BDI14

between males and females. Aziz et al17 showed male gender was associated with CBD

injury in a univariate model but it was nonsignificant in a multivariate analysis.

Causes and risk factors for BDI

When reported, the most frequent cause of BDI in the studies1,12,20 was anatomical

misunderstanding, specifically misinterpreting the common bile duct with the cystic duct.

Some studies18,20 refer risk factors for BDI. Besides male gender16,17,19, the most

mentioned risk factors were local inflammation and acute cholecystitis, older age (>65

years), anatomical abnormalities, chronic cholecystitis, using a 0º laparoscope,

hemorrhage, emergent cholecystectomy and obesity.12,16,17,19,20 Karvonen et al15 refers to

acute and chronic cholecystitis as a frequent technical problem. Fullum et al16 did not find

acute cholecystitis associated with BDI, but it increased mortality.

Management of BDIs

Seven studies mention BDI management1,15–20. Three separate the management

of lesions by the time of its recognition (intraoperative and postoperative) and type of

lesion1,18,19. The most frequent procedures when dealing with intraoperative diagnosis

were suture by laparoscopy or conversion to laparotomy (end-to-end anastomosis and

Roux-en-Y hepaticojejunostomy). When the recognition was made after the LC, patients

were mostly treated by percutaneous drainage, stenting by endoscopic retrograde

cholangiopancreatography (ERCP), sphincterotomy and laparotomy for biliodigestive

anastomosis.

  6  

Karvonen et al15 didn't specify the time of diagnosis but described management by

type of BDI lesion by Amsterdam criteria. Type A lesions were treated endoscopically, the

majority by sphincterotomy and biliary stenting. Most type B underwent laparotomy (2

immediately, 2 later) mostly for a T-tube suturing or endoscopic stent. Type C lesions

were mostly treated by endoscopic measures (dilatation and stenting). The majority of

patients who sustained type D injuries underwent hepaticojejunostomy or

cholangiojejunostomy.

One study20 mentioned T-tube repair, primary suture and suture ligation as the

most frequent procedures for BDI repairing. Two studies16,17 mention only ICD codes and

do not specify their frequency. Nevertheless, the procedures include simple suture of

CBD, biliodigestive anastomosis, ERCP, choledochoplasty and repair of other bile ducts.

Mortality related to BDI

Only 6 studies1,12,15,18–20 reported mortality related to BDIs. Savassi-Rocha et al18

reported a 4,2% rate (7 deaths out of 167 patients), Karvonen et al15 reported a 3,1% rate

(1 out of 32 patients) and Malik et al20 a 5,3% rate (1 out of 19). Demartines et al1,

Richardson et al12 and Tantia et al19 reported no deaths.

Intraoperative cholangiography to identify IOC

Demartines et al1 reported routine use of IOC until 2006. From the 13 BDIs, IOC

was performed in 8 patients and helped identify 3 injuries, confirmed a suspected BDI in 3

cases and was misinterpreted (as normal) in 2 cases. Savassi-Rocha et al18 reported

routine IOC allowed the surgeons to identify 19,5% of BDIs. When this exam was only

selectively performed, 28,3% of BDIs were identified.

Richardson et al12 reported selective use of IOC and authors referred that IOC was

not important in the identification of BDI.

Other studies that mention IOC performed it in selected cases only13,14,19 or did not

provide full information related to this procedure16,17.

Discussion

Biliary duct injury has been proposed as the most serious and potentially life-

threatening complication of cholecystectomy.24

Since the implementation of LC, studies have shown an increased rate of this type

of surgery2,25,26. In 1993, the NIH Consensus conference considered it a safe and effective

treatment for most patients with symptomatic gallstones and it remains the treatment of

  7  

choice for many patients since.27,28 Cholecystectomy is nowadays one of the most

commonly performed abdominal surgeries and, in the USA, 90% are performed

laparoscopically.29 LC results in less postoperative pain, faster recovery and shorter

hospital stay and has less impact on physical appearance than OC.30–32

A considerable disadvantage of this procedure has been the incidence of

BDIs4,5,20, which is proclaimed by some to have increased as a "learning curve" effect but

has remained high even after that period of time3,4,20. Some studies state the incidence of

BDI has increased from 0,2 to 0,5% from its debut to its regular use and, accordingly, it is

higher than BDI after OC.4,8,33 This is contradicted by other studies that report an

improvement of this rate over the last years.34,35

Although its incidence is, nevertheless, low, BDIs increase morbidity and mortality

and decrease the quality of life of patients, specially the patient’s mental health36–39.

Awareness of this important repercussion turns mechanisms for its prevention,

identification and treatment very important. Studies have been made to define risk factors

for BDI after LC, including (but not limited to) obesity, age, male gender, severe

inflammation or infection and surgeon’s experience.4,14,16,17,29 After injury has occurred,

management will depend on the type and extent of BDI and timing of its diagnosis. Early

referral to a tertiary center for a multidisciplinary approach seems to be important.40,41

Incidence

Over the decades after LC started being used, a lot of studies have reported BDI

incidence, which has been varying considerably. Among the first larger series published,

Deziel et al5 reported a 0,60% BDI rate after 77604 LC and MacFadyen et al7 a 0,50%

incidence of major BDI in a total of 112532 cases. The fact that both studies exclude

cystic duct injuries may underestimate BDI. In 1960, Rosenqvist and Myrin figured that the

incidence of BDI after the traditional OC in Sweden would vary between 0,25-0,33%,

Madsen et al estimated an incidence of 0,31% in Denmark and Viikari a 0,20% incidence

in Finland.42 These large series agree with the vast body of literature that has reported LC

was associated to a higher BDI incidence than OC during the first years after it started

being used.

In this review, the overall incidence of 0,63% reported by Richardson et al12

between 1990 and 1995 support the previously mentioned LC series. The incidence

peaked at 0,80%, but it should be mentioned that this value fell to 0,40% in 1995. In

contrast, Savassi-Rocha et al18 report a lower incidence, harmonious with OC rates, but

they exclude cystic duct injuries. If included, they would increase the incidence of BDI to

0,27%. This rate would still be comparatively low, but one should be careful in comparing

these 2 studies. Although Savassi-Rocha et al18 was conducted between 1990 and 1997,

  8  

more than 80% of units had already performed more than 100 operations at the time of

the survey (almost 40% had performed more than 500 LCs) and Richardson et al12

include data since this type of procedure was launched in the West of Scotland hospitals.

Analyzing the studies included in this review, it appears that, as time went by, the

incidence of BDI increased. Grönroos et al14 reported a rate of 0,86% and Veen et al13

1,20%. It should be taken into consideration that the majority of injuries reported in both

studies were type A Amsterdam criteria (leakage from the cystic duct or peripheral hepatic

radicals) or type A Strasberg (bile leak from cystic duct or liver bed without further injury),

which can be relatively easily treated.

Malik et al20 report a BDI incidence of 1,68%. Among the 19 BDIs, 1 injury was

clipping of the CBD instead of the cystic duct, which was recognized and removed

immediately. The authors discussed that, in their experience, majority of injuries could be

avoided by simple measures like lowering the threshold for conversion to OC when

identification of anatomical parts is difficult. They also concluded surgeon's over-

confidence and casual attitude in operating rooms should be further evaluated. They do

not report the rate of conversion in the study, so it is not possible to conclude if it was

lower than other series.

On the other hand, Fullum et al16 report an overall incidence of 0,06%. They could

not account for BDIs in patients who were diagnosed after discharge (important aspect

since the length of stay is shorter for LC than OC), only if they were still hospitalized.

Furthermore, they could not include LCs where a BDI was noticed and the procedure was

converted to an open approach for repair, as it would be coded in the database as an OC.

They also report a decrease of BDI incidence after all cholecystectomies (laparoscopic

and open procedure). This is important because the rate of OCs decreased from 19,5% in

the initial 3 years of the study to 15,1% in the last 3 years.

The two longest studies1,19 report similar BDI incidence (0,39% and 0,46%) even

though they differ on the time period they comprised. This is an overall rate and, as such,

one cannot realize if BDI actually increased or not.

Aziz et al17 report a rate of 2,55%. This value is completely different from what one

can find in most literature. It is worth mentioning that, in this study, acute cholecystitis

represented 41% of the pathologies requiring LCs, which has been proposed by some as

a risk factor for BDI in LCs. Emergent LCs represented 61% of the total number of LCs,

which has also been proposed as a risk factor for conversion to OC and adverse

outcome43,44. The authors also explained that the database made preexisting comorbid

factors difficult to separate from postoperative complications.

Browsing the literature, one can find that a substantial number of studies cite an

incidence of BDI after OC of 0,1 to 0,2%. As mentioned before, some older studies report

  9  

rates between 0,20 and 0,33%42. Additionally, in a large series of 36278 surgeries, Waage

et al4 report an incidence of 0,40% in the years preceding the introduction of LCs (1987 to

1990). Similarly, Diamantis et al34 report a 0,38% incidence of BDI after OCs between

1991 and 2001. Therefore, it can be inaccurate to assume that the incidence of BDI after

OC is as low as it has been stated in literature, as it may differ. Other important aspect is

that, in older OC series, like the ones discussed previously, the same definitions of BDI

may not have been rigorously applied. Another condition to consider, when reading any

study, is the frequent selection bias; patients who undergo OC may be different from the

ones undergoing LC.

Although the incidence of BDI after LC appears to have been higher during the first

years, it is difficult to define a specific value for its incidence after reading the studies

presented here as the rates vary greatly. The patients included in the studies, the

methodology, access to databases and follow-up information differ considerably. In this

review, the largest series have lower rates of BDI incidence. Considering the conditions of

each study and the incidence of BDI after OCs mentioned previously, it appears that BDI

incidence after LC is found to be slightly higher than that of OC. One can realize it is,

anyway, a very low value.

Classification of BDI

Several classifications have been used to help describe the injuries, the most used

being Bismuth and Strasberg classifications. The categories are an useful tool to the

surgeon since they help in choosing the most adequate management procedure to repair

the injury and to compare their outcomes.45,46

Proposed in 1982, in the era of open cholecystectomy, the Bismuth classification

has since been widely used.45 It is based on the level of the injury, at which non-damaged

bile ducts are available for anastomosis, and is known to have a good correlation with the

outcome after injury management.46,47 It divides BDIs into five types (table I).45

With the onset of LC, the Bismuth classification was not able to include the range

of BDIs that could possibly develop. Isolated right hepatic duct strictures, other strictures

and leakage from the cystic duct could not fit into this system. In 1995, the Strasberg

classification expanded on the Bismuth classification and brought new categories that

could be applied to those injuries (table II).47,48 Therefore, the Strasberg-Bismuth

classification includes types A to E and allows differentiation between small and severe

injuries. Type E BDIs are subdivided into E1 to E5 under the Bismuth classification.

Although it can be easily applied, it does not express possible vascular engagement.49

Also in 1995, McMahon et al50 proposed a classification of minor or major injury

based on the width of BDI. Laceration under 25% of the bile duct diameter or buttonhole

  10  

tear were classified as minor, and laceration of over 25% (or transection) of CHD or CBD

or postoperative stricture were classified as major injuries. In 1996, the Amsterdam

Academic Medical Center's classification was proposed by Bergman et al (table III). It

divides injures from type A to type D.51

Other classifications have been suggested, like the ones proposed by Olsen

(1997)52, Martin et al53, Neuhaus et al45 (2000), Csendes et al (2001)54, Stewart et al

(2004)55 and Lau et al (CUHK classification) (2007)46. The last 2 include vascular

injuries.46

Bektas et al proposed the Hannover classification in 2007.56 It includes vascular

injuries, has determinants for the location of the damage and demonstrates an association

between BDI pattern and surgical repair and also with the resection of liver tissue and

hepatic duct bifurcation.45

The studies included in this review use different BDI classifications. For that

reason, it is difficult to bring together all their results. One can observe that the most

frequent type of injury found was Strasberg type A or "cystic duct injuries".1,13,14,18,19 This

reflects the trend reported by other studies.5,57 Hence, although the incidence of BDI found

in some studies was higher than what one would expect, the majority of injuries inflicted

were minor BDIs. In these cases, the bile ducts are in continuity with the biliary tree, which

allows a possibly easy management.58 Type D injury was the second most frequent

injury.1,18,19 In this type, the continuity of the biliary duct is kept as well, and its repair will

depend on the vascularization of the duct.

Some studies1,13,18,19 also report type E lesions, with Savassi-Rocha et al reporting

a majority of Bismuth types 1 and 2. Type 1 is an anatomically low injury which can be

treated without lowering the hilar plate46. On the other hand, under the McMahon

classification, the majority of lesions reported by Richardson et al were considered major,

but the number was almost equal to the minor injuries.12 Still, this is an older study and the

learning curve period may have an impact on the severity of the lesions. The authors also

refer that if only major BDI is included, the rate would be comparable to retrospective OC

series.12 In spite of the results of these studies, a prospective study by Dorcaratto et al59

concluded that BDI occurring during LCs is becoming more complex as surgeons perform

more difficult LCs, and vascular injuries are becoming more common.

The incidence of vascular injuries found in literature varies greatly. While in a

series of autopsies Halasz et al60 reported a 7% incidence of arterial injury in patients that

had sustained OC, Alves et al61 reported a 47% incidence of vascular injury in patients

who had suffered BDI during LC. This is understandable, specially, after realizing that the

most affected vessel is the right hepatic artery (RHA)55,61,62, because as BDI due to LC are

more proximal in the biliary tree, they get closer to the location of the RHA55. Yet, Alves et

  11  

al61 mention a series of OCs where routine angiography was carried out and referred that

the authors found an incidence of vascular injuries of 39%. Regarding the present review,

one can not draw any conclusion since the studies did not mention these injuries nor used

a classification that included these types of injuries.

Studies have also reported that outcome is worse in patients who have a BDI with

a concomitant vascular injury compared to patients with BDI only, with a higher incidence

of abscess, hemobilia and hepatic ischemia and resection.55,63 Bilge et al62 found that the

frequency of complex BDI was higher when there was a concomitant vascular injury, but

concluded it had no significant effect on mortality and BDI repair. While an injury that

damages the blood supply of the ducts can cause complications due to local ischemia,

unilateral injury to the hepatic blood vessels, usually, does not cause complications, and

may therefore remain undetected, because blood can circulate via the hilar plexus. This

could explain why the management is comparably successful in patients with and without

vascular injury, particularly with a Hepp–Couinaud approach.61 Hence, Bilge et al62 did not

recommend routine use of angiography. Alves et al61 justified their high incidence with the

routine use of angiography, but added that it had no impact on the presentation of the BDI

or on treatment failure.

Patient gender

Male gender has been proposed as a risk factor for adverse outcomes in LC.64 In a

systematic review, Hu et al43 verified that male gender was considered a risk factor for

conversion to open procedure in several studies. Waage et al4 also found that male

gender was associated with a bigger risk of BDI in cholecystectomy. Kanakala et al44 also

found male gender was a predictor of morbidity, mortality and conversion to laparotomy

and proposed that they have a higher threshold of pain, are older and present later as

they have a more delayed presentation of disease. On the other hand, Kumar et al65 did

not find male gender statistically significant as a risk factor for BDI during LC.

In this review, the data concerning patient's gender, available in 4 studies, shows

that most BDIs occurred in female rather than male patients. In one of those studies,

Grönroos et al14 concluded that female gender is a risk factor for severe BDI in LC, but

they did not find statistically significant the difference in risk. Aziz et al17 showed male

gender was associated with CBD injury in an univariate model, but it was revealed to be

nonsignificant in a multivariate analysis. Tantia et al19 concluded male gender may

increase the chances of BDI. Hence, these studies do not dispute the literature that

supports male gender as a risk factor for adverse outcome in LC.

  12  

Causes and risk factors

In literature, one can find several factors associated with an increased risk of poor

outcome, conversion to OC and BDI, including male sex, age, obesity, acute cholecystitis,

comorbidities and emergency laparoscopy.43,44 It is frequent to find acute cholecystitis,

emergency LC and surgeon's narrow experience with LCs associated with BDI.8,66,67

When comparing literature with the results seen in the studies here included, it is not

surprising that the most mentioned cause of BDI was misidentification of CBD as the

cystic duct (the "classic injury"). Shallaly and Cuschieri47 highlight that these injuries could

be avoided if the surgeon identifies with certainty every anatomical struture. Other

anatomical mechanisms found in literature include lateral clipping of the CBD, traumatic

avulsion of the cystic duct junction and injury by diathermy of the CBD while dissecting

Calot's triangle.24

Inflammation was also a frequent mentioned cause, which is supported by

literature68. One can conclude that situations that further complicate LCs are indeed

causes that facilitate BDI. Nuzzo et al8 found that BDI associated with cholecystitis

occurred more in surgical teams with greater experience. These stress the importance of

evaluating risk factors and taking caution intraoperatively.

Mortality after BDI

Most mortality rates related to BDI in the series here included15,18,20 are slightly

higher that the ones presented in other studies7,40,41. Sicklick et al41 reported 1,7%

mortality early after definitive repair procedures, 1,5% due to sepsis (without a repair

procedure) and De Reuver et al40 found it to be 2,4%. Flum et al69 found that BDI

increased the likelihood of death within 10 years by 3 times. These studies40,41,69 highlight

the importance of tertiary center referral after BDI.

Management of BDI

The management of BDI is determined by the time of diagnosis and the type and

extent of the injury. An early diagnosis of BDI is important as it can avoid complex repair

procedures and complications like infection and fibrosis.70 Different studies33,51,71 have

recognized that only a minority of injuries, usually less than 30%, is recognized during the

initial procedure. In the studies presented in this review, the proportion of injuries detected

intraoperatively was almost equal1,12 or even higher18,19 than the ones detected

postoperatively. However, some injuries may present months or years after surgery48,

which means rates can change with long-term follow-up.

The success of repair is associated with a complete assessment of the anatomic

area involved before an attempt to repair the injury.72 Stewart et al72 reported that 96% of

  13  

BDI repairs were unsuccessful when cholangiograms were not obtained preoperatively,

but, when data was complete, 84% were successful. Thus, the anatomical area should be

investigated and the procedure for reconstruction should be carried out by a specialist

with experience in these procedures in order to achieve the best results72. Usually the

repairs are conducted best if other surgeon, different than the one who performed the first

LC, performs the repair.33

BDI recognized during the LC

BDI can be recognized directly, by intraoperative cholangiogram, or suspected by

the leakage of bile. If recognized, the surgeon should assess its severity and look out for

vascular injuries. He has to decide whether to repair it immediately or to refer the patient

to a specialist surgeon. Some BDIs, like cystic duct and gallbladder bed leaks and partial

duct lacerations, can possibly be managed right away by the surgeon, but this will depend

on their training and skills72. In the studies included in this review, while Demartines et al1

converted to laparotomy half of the cases diagnosed intraoperatively, Savassi-Rocha et

al18 showed a greater frequency of conversion to laparotomy. Tantia et al19 performed the

immediate repairs by laparotomy if there was a complete transection of a duct, but did

mostly by laparoscopy if the injury was lateral or sectorial.

Referral to a specialist surgeon with experience in BDI repair improves

prognosis72,73, and the patients' best interests should be kept in mind. If a biliary specialist

is needed but not available, a subhepatic drain can be placed and referral to an

hepatobiliary unit should be made as soon as possible.33 The European Association for

Endoscopic Surgery (EAES) guidelines suggest that a conversion to OC should only be

made by a biliary specialist after the confirmation of injury or to control hemorrhage in

cases of severe bleeding.74 The EAES recommend all injuries should be referred, except

leakage from cystic ducts or from the liver bed, which can be treated endoscopically.74

Additionally to bile leakage or hemorrhage, there are signs that may help suspect

a BDI will occur, like apparent ductal or anatomical abnormalities (may indicate the CBD is

being dissected instead of the cystic duct), an extra bile duct (could be the CBD or a

transected CHD), cholangiographic abnormalities (cholangiocatheter positioned in the

CBD) or a large artery posterior to the cystic duct (could be the RHA and actually the

CBD).33 Thus, a surgeon should keep in mind at all times the event of BDI in LC.

Archer et al75 reported that BDIs were more likely to be discovered during surgery

when a cholangiogram was obtained. The EAES guidelines state IOC and laparoscopic

ultrasonography (LUS) bring valuable information to the surgeon and advocate its use

when there are concerns about the biliary tree anatomy.74 IOC can detect CBD stones70

and find BDIs if they occur and LUS may also allow earlier recognition and their repair.76

  14  

BDI recognized postoperatively

Reviews and studies33,51,52,77 have reported the majority of BDIs are diagnosed

postoperatively. The main 2 injury types are bile leaks and biliary obstructions, which can

occur at the same time. As recovery from LC is frequently easy, the presence of BDI

should be investigated when the patient has symptoms that do not improve over time.33,74

Bile leaks usually present within the first few days or weeks after LC with vague

and mild symptoms, including a feeling of abdominal fullness, nausea, vomiting, fever,

and possibly abdominal pain.64 They usually do not cause severe peritoneal irritation64,

but can ultimately lead to bilomas, biliary fistulas, cholangitis or sepsis41, although bile

peritonitis with extreme manifestations is uncommon early after surgery even with large

amounts of bile77. Liver enzymes and bilirubin are usually normal.33,77 Hence, the

diagnosis can be difficult to establish. Lee et al77 reported bile collections were initially

missed in 77% of patients with BDI after LC as the clinical picture was nonspecific, and

the mean time to the diagnosis was 16,8 days. This is of utmost importance as they also

reported that later bile drainage (more than 10 days after LC) was associated with a

higher incidence of severe illness and positive bile cultures.77 Because bile can

accumulate even when a drain is placed at the time of the cholecystectomy, imaging

studies should be requested when there is a suspicion of BDI, that is, when the recovery

of LC is not smooth.77 Some studies report that, in the first days after LC, a small

collection of fluid can be found at the gallblader fossa.78,79

The presentation of obstruction is usually one of jaundice, anorexia, and

abdominal pain. Laboratory analysis may also show a cholestatic pattern.51,64 Studies

have reported alanine aminotransferase and alkaline phosphatase levels can be elevated

in the first days after LC, possibly because of the pneumoperitoneum inherent to the

procedure, but these are clinically insignificant and do not predict complications.80,81 In a

partial occlusion, the parameters of cholestasis can also decrease to the normal range

after 10 days.74 Biliary strictures can take months or years to develop and, when present,

can cause cholangitis, jaundice and cirrhosis.41

The EAES reccomend the use of computed tomography (CT) scan or ultrasound

(US) as the first choice to search for intra-abdominal bile collections and ductal

dilatations.74 These methods can detect fluid collections although they do not distinguish

the type of fluid present or its continuity with the biliary tree.82 Chole-scintigraphy scans

can detect an active bile leak but they have some disadvantages, like poor anatomical

definition, and consequently they become dependent on another imaging procedure.82 If

bile collections are present, they should be drained and cholangiography should be done

to visualize the ducts.74 ERCP can be therapeutic (allows for stenting or dilatation)82 and is

  15  

the recommended procedure.74 Percutaneous transhepatic cholangiography (PTC) or

magnetic resonance cholangiopancreatography (MRCP) are useful when a complete

obstruction is present, as ERCP won't be able to visualize the proximal biliary ducts in

such case.74,82 PTC also allows for dilatation and stenting and can help in decompressing

the proximal biliary tree.74,83 MRCP can be better in the diagnosis and can help choosing

the best management procedure, but has also some disadvantages.82,84

As in the case of BDI diagnosed during LC, concomitant vascular injuries should

be searched for because they can change the management strategy. Duplex US has

been referred as a non-reliable method to access these lesions, making room for

angiography.85 MRCP with hepatobiliary contrast material can provide this information.82

Besides the complete assessment before attempting to repair an injury and the

experience of the surgeon, the success of BDI management also correlates with the

elimination of abdominal infection and the use of an adequate surgical technique.73

Therefore, another goal before pursuing BDI repair is to control peritonitis or sepsis if they

are present.64,83 Electrolyte and nutritional status should be corrected and fat-soluble

vitamins supplemented.64 Although one can find literature supporting a waiting period of

time for repairing the BDI in order to decrease inflammation83, like 2 to 3 months64, a

multivariate analysis by Stewart et al73 concluded that timing does not correlate with the

success of management, hence there is no reason to delay it when all of these conditions

meet.

The management can be done endoscopically or surgically. Small injuries like

cystic stump or accessory bile duct leaks can be treated endoscopically with stenting and

drainage of collections, insertion of a nasobiliary drain (NBD) or sphincterotomy.86–88

Stenting and sphincterotomy are done to allow better flow of bile to the duodenum and

decrease its pressure inside the ducts, allowing the injury to heal, and can be done

together.88 NBDs decrease pressure inside the biliary tree and allow further

cholangiographies but can be uncomfortable, can dislodge and the patient is compelled to

stay hospitalized until they are removed.89 Although the endoscopic procedures have

been shown to be safe86,89–91, there are no studies comparing these procedures. Kaffes et

al92 concluded that stenting was superior to sphincterotomy, but one can point out some

limitations in the study93. In a series of 207 patients, Sandha et al88 applied different

approaches for high and low grade bile leaks with good outcomes. It is known that

stenosis can occur after the stent is removed71 and that sphincterotomy carries a risk of

acute and long-term complications94. In the absence of lesions, like a retained stone, the

EAES and the European Society of Gastrointestinal Endoscopy (ESGE) advocate stenting

should be done without sphincterotomy74,95. When removing stents, Pioche and

  16  

Ponchon70 advise execution of new cholangiograms in order to guarantee the ducts are

free of obstructions.70

Bile duct strictures can also be repaired with endoscopic stenting.51,87,89,96 Studies

support that it can be an alternative to hepaticojejunostomy96 and that the use of multiple

stents can improve outcomes97. While the rate of recurrent stricture was found to be

around 20% after 2 years in a study98, Costamagna et al97 reported no cases of

recurrence with the use of a more aggressive approach (up to 6 stents). In the case of

strictures, the ESGE recommends the use of temporary stents.95 In any of the approaches

mentioned before, the advantages and disadvantages of each procedure should also be

discussed with the patients95. If the endoscopic approach fails, then hepaticojejunostomy

can be performed. In a study99 concerning OC patients, early complications were found to

be more common in the surgically treated patients, while there were more late

complications in the endoscopically managed patients (including stent migration) and both

strategies had similar success rates.

Partial bile duct lacerations recognized at the LC can be repaired with simple

suture repair and drainage.51,71,83 Some authors advocate suture over a T-tube64, while

others state that it can enlarge the laceration and later evolve into a stricture33.

Discontinuity with the bowel will require a surgical approach.64 In the case of a complete

transection (or a large laceration) of the CBD or CHD, there can be more loss of tissue

and it is more likely that the biliary microvasculature could be damaged71,83. A primary

end-to-end anastomosis has been shown to be unsuccessful in these cases as it will

frequently be under tension, even with mobilization of the duodenum, in combination with

the possible decrease in blood supply, and later evolve into a stricture.64,72 Savassi-Rocha

et al18 showed end-to-end anastomosis was performed in 26,3% of BDIs, but authors

stressed the importance of long follow-up in order to identify late complications, such as

strictures. In the majority of cases, a Roux-en-Y hepaticojejunostomy is the preferred

procedure,71,83 and the Hepp-Couinaud approach can be of particular interest for injuries

where the confluence is intact.64 As mentioned before, if there is no specialist surgeon

available at the time of the LC, drains should be placed and the patient referred to a

specialized unit.

In general, the studies in this review which address BDI management1,15,18,19 and

follow-up adopted these principles. None concluded if any therapy was superior to any

other. Demartines et al1 performed stenting as a first line treatment, when possible,

followed by surgical repair if the first one failed, and reported good results, without the

need of liver resection or transplant. As a therapy for stenosis, Savassi-Rocha et al18 did

not conclude which type of repair was better, but highlights that, in tertiary referral centers,

surgical management achieved a 96% success rate. At the time of the survey, they

  17  

reported 87,4% patients were asymptomatic.18 In the study by Karvonen et al15, only 1

patient suffering from stricture (12%) required hepaticojejunostomy after endoscopic

treatment. Tantia et al19 reported only 2 patients (3,85%) had recurrent symptoms

(cholangitis) after treatment in a 24-month follow-up. These findings in different studies

support the management strategies mentioned before.

Hepatic or sectoral duct injuries can be difficult to detect. A cholangiography may

seem normal because of the absence of contrast leakage and the presence of a normal

right and left ducts' confluence.83 There is also the possibility of anatomic variations of the

biliary tree, which would make it harder to correctly identify the biliary ducts during LC.71

The resulting biliary leakage should be drained in order to avoid development of more

severe conditions and elective surgical repairing of the injured duct done by a specialized

surgeon as a Roux-en-Y hepaticojejunostomy.100 Although the Hepp-Couinaud approach

is useful for left sided injuries, some studies101,102 used this method to right sided injuries

as well, with good results. If these approaches fail, then liver resection can be

envisaged.83

In a review, Tzovaras and Dervenis103 refer vascular injuries during LCs have been

associated with bleeding, difficult BDI repair and strictures. The most frequent injured

blood vessel during LC is the RHA, which is usually lying posteriorly to the CHD.103

Because of the architecture of the hepatic circulation, an injury to the RHA can remain

unnoticed.71,83 Some authors even suggest not to repair this injury because it rarely has

consequences, if the liver is otherwise healthy.64,103 With an associated bile duct injury,

some state BDI can be repaired without the reconstruction of the artery.55 Others highlight

the possible liver atrophy and necrosis, which would need resection or

transplantation104,105.

Intraoperative Cholangiography

In addition to showing the biliary tract anatomy and detecting CBD stones, IOC

can help recognize BDIs.70 However, its routine use is controversial because of the lack of

randomized studies reporting a decrease in BDI incidence in this scenario. IOC increases

LC time and costs, and is susceptible to error, like incision of the CBD instead of the cystic

duct, which could itself lead to an injury.70 Even in this case, the IOC could help identify

this injury, if it would be interpreted in the correct way by the surgeon. In the series by

Demartines et al1 it was reported that IOC provided BDI identification in 3 out of 8 BDIs,

but other 2 IOCs were interpreted as normal when, in fact, there was an injury. Some

studies report an association between performing routine IOC and a decrease in BDI106,

but in order to understand if there is a causal relationship between these factors then

variables, confounders and effect modifiers should be taken into account.107

  18  

In this review, Savassi-Rocha et al18 reported 19,5% of BDIs were identified

because IOC was routinely performed. Yet, they also mention that 47,8% of the BDIs

were identified before the actual routine IOC took place. This means that, when it was

routinely used, 66,7% of BDIs were identified prior to the procedure. The authors

concluded that the majority of diagnoses were made without the use of IOC.

While there are no studies exploring this subject, it appears that the best conduct

is to make use of an adequate surgical technique and decide whether to perform IOC or

not as already mentioned by the EAES74. It is important to stress that IOC cannot prevent,

by itself, a BDI.107

Conclusion

Bile duct injury is one of the most relevant problems of laparoscopic

cholecystectomy. Its incidence appears to have remained slightly higher than in the era of

open cholecystectomy, but most injuries are not complex, and most patients experience

resolution of symptoms after proper management. Risk factors should be considered

before surgery. The most frequent cause for BDI was misunderstanding anatomical

structures, something surgeons should keep in mind. Surgical management should be

done by experienced surgeons in specialized units. Routine intraoperative

cholangiography is a matter of debate but appeared not to be important.

  19  

Figures

Figure 1. PRISMA flow diagram.

  20  

Tables

Table I. Bismuth's classification of bile duct injury

Type Criteria

1 Low CHD stricture, with a length of the common hepatic duct stump of >2 cm

2 Proximal CHD stricture-hepatic duct stump <2 cm

3 Hilar stricture, no residual CHD, but the hepatic ductal confluence is preserved

4 Hilar stricture, with involvement of confluence and loss of communication

between right and left hepatic duct

5 Involvement of aberrant right sectorial hepatic duct alone or with concomitant

stricture of the CHD

Table II. Strasberg's classification of bile duct injury

Type Criteria

A Cystic duct leaks or leaks from small ducts in the liver bed

B Occlusion of a part of the biliary tree, almost invariably the aberrant right

hepatic ducts

C Transection without ligation of the aberrant right hepatic ducts

D Lateral injuries to major bile ducts

E Subdivided as per Bismuth's classification into E1 to E5

Table III. The Amsterdam Academic Medical Center's classification of bile duct injury

Type Criteria

A Cystic duct leaks or leakage from aberrant or peripheral hepatic radicles

B Major bile duct leaks with or without concomitant biliary strictures

C Bile duct strictures without bile leakage

D Complete transection of the duct with or without excision of some portion of the

biliary tree

  21  

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