Journal Name: International Journal of Hepatobiliary and … · 2018-12-07 · 8 Hourneaux de Moura...

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Early View Article: Online published version of an accepted article before publication in the final form.

Journal Name: International Journal of Hepatobiliary and Pancreatic Diseases (IJHPD)

Type of Article: Original Article

Title: Endoscopic palliative treatment versus surgical bypass in malignant low bileduct obstruction: A systematic review and meta-analysis

Authors: Silvia Lucia Alves de Lima, Fabio Alberto Castillo Bustamante, Eduardo

Guimarães Hourneaux de Moura, Wanderley Bernardo Marques, Everson Luiz de

Almeida Artifon, Dalton Marques Chaves, Tomazo Antonio Prince Franzini, Carlos Kiyoshi

Furuya Junior

doi: To be assigned

Early view version published: April 6, 2015

How to cite the article: Alves de Lima SL, Bustamante FAC, Hourneaux de Moura EG, Marques WB, de Almeida Artifon EL, Chaves DM, Prince Franzini TA, Furuya Junior CK. Endoscopic palliative treatment versus surgical bypass in malignant low bileduct obstruction: A systematic review and meta-analysis. International Journal of Hepatobiliary and Pancreatic Diseases (IJHPD). Forthcoming 2015.

Disclaimer: This manuscript has been accepted for publication. This is a pdf file of the Early View Article. The Early View Article is an online published version of an accepted article before publication in the final form. The proof of this manuscript will be sent to the authors for corrections after which this manuscript will undergo content check, copyediting/proofreading and content formatting to conform to journal’s requirements. Please note that during the above publication processes errors in content or presentation may be discovered which will be rectified during manuscript processing. These errors may affect the contents of this manuscript and final published version of this manuscript may be extensively different in content and layout than this Early View Article.


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TYPE OF ARTICLE: Original Article 1

2

TITLE: Endoscopic palliative treatment versus surgical bypass in malignant low 3

bileduct obstruction: A systematic review and meta-analysis 4

5

AUTHORS: 6

Silvia Lucia Alves de Lima1, Fabio Alberto Castillo Bustamante2, Eduardo Guimarães 7

Hourneaux de Moura3, Wanderley Bernardo Marques4, Everson Luiz de Almeida 8

Artifon5, Dalton Marques Chaves6, Tomazo Antonio Prince Franzini7, Carlos Kiyoshi 9

Furuya Junior8 10

11

AFFILIATIONS: 12

1MD Gastrointestinal Endoscopy Unit, Hospital das Clinicas, University of Sao Paulo 13

Medical School. São Paulo, São Paulo, Brazil. Email ID: [email protected] 14



3Head Teacher Gastrointestinal Endoscopy Unit, Hospital das Clinicas, University of 17

Sao Paulo Medical School. São Paulo, São Paulo, Brazil. Email ID: 18

[email protected] 19

4Methodological Adviser Gastrointestinal Endoscopy Unit, Hospital das Clinicas, 20

University of Sao Paulo Medical School. São Paulo, São Paulo, Brazil. Email ID: 21





Medical School. São Paulo, São Paulo, Brazil. Email ID: 26






32


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CORRESPONDING AUTHOR DETAILS 33

Fabio Alberto Castillo Bustamante, MD, 34

Gastrointestinal Endoscopy Unit, Hospital das Clinicas, University of Sao Paulo 35

Medical School. São Paulo, São Paulo, Brazil. 36

Adress Av Dr Enéas de carvalho Aguiar 255 andar bloco 03, Postal Code 05403900. 37

Contact Phone Number: 1126616221, Fax Number: 1126616463 38

Contact Email ID: [email protected] 39

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Short Running Title: Malignant bileduct obstruction metanalysis 41

42

Guarantor of Submission : The corresponding author is the guarantor of 43

submission. 44

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ABSTRACT 67

Aims: 68

Despite technological advances, only about 20% of periampullary tumors are found 69

to be resectable at the time of presentation. Biliary tree obstruction and consequent 70

jaundice occur in 70–90% of those patients and has important consequences for a 71

patient’s quality of life. Relief of biliary tree obstruction is the main goal for treatment, 72

and few options for palliative therapy of biliary tree obstruction can be performed, 73

including surgical bypass, percutaneous stenting, and endoscopic stenting. 74

Objective: The aim of the present study is to acquire and analyze data to compare 75

the success of procedures, procedure-related complication, mortality in 30 days, 76

recurrent-jaundice rates in endoscopic, and surgical palliative techniques. 77

78

Methods: 79

Two independent reviewers searched the following electronic databases: Medline, 80

EMBASE, Cochrane, LILACS, BVS, SCOPE, and CINAHL (EBSCO). Inclusion 81

criteria included studies involving patients with distal biliary obstruction due to 82

periampullary tumors who underwent endoscopic therapy or a surgical procedure for 83

palliation. 84

85

Results: 86

No differences were observed for success of procedures; differences were observed 87

with better outcomes for endoscopy therapy with regards to mortality associated with 88

procedure, complication associated with procedure, and mortality in 30 days. Also, 89

differences were observed with better outcomes for surgery therapy for recurrent-90

jaundice. 91

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Conclusion: 96

Endoscopic palliative drainage is associated with a lower rate in complication, 97

mortality associated with procedure, and mortality in 30 days. Recurrent-jaundice 98

analysis demonstrated an overall lower rate in surgical bypass procedures. No 99

differences were found for the success of procedures. 100

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Keywords: Periampullary Tumors; Bile Duct Cancer; Cholangiocarcinoma, 102

Pancreatic Carcinoma; Endoscopy, Gastrointestinal; Surgical Procedures, Operative. 103

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INTRODUCTION 130

Jaundice due to biliary obstruction is usually the main symptom at the time of 131

diagnostic in periampullary cancers. Despite technological advances, only about 132

20% of periampullary tumors are found to be resectable at the time of presentation. 133

Biliary tree obstruction and consequent jaundice occur in 70–90% of those patients 134

and has important consequences for a patient’s quality of life. Because of this dismal 135

natural history, palliation remains the principal management in such patients, and 136

relief of biliary tree obstruction is a prime concern [1, 2]. 137

Few options for palliative therapy of biliary tree obstruction can be performed, 138

including surgical bypass, percutaneous stenting, and endoscopic stenting. Although 139

initial results with surgical bypass demonstrated low rates of recurrent jaundice (2–140

5%), the surgery itself carries an appreciable risk of post-operative morbidity and 141

mortality, up to 24% in some trials [3,4]. Surgical decompression has been 142

advocated in patients who at the time of laparotomy for planned tumor resection are 143

found to have unresectable disease as well as in occasional patients with longer 144

projected survival [5, 6]. Advances in minimally invasive therapy have led to the 145

development of luminal stents whose insertion can relieve jaundice and hence avoid 146

the need for surgery [7, 8, 9]. 147

Early biliary stents came in the form of a plastic prosthesis that was inserted across 148

the obstructing mass to provide drainage of the biliary tree; however, bilioduodenal 149

reflux and food fibers result in stent blockage. Various changes in plastic stent 150

design and adjunctive therapy such as antibiotics have failed to significantly improve 151

their patency [10]. With a wider bore than plastic stents, several studies have shown 152

that they exhibit superior patency to plastic stents [11, 12, 13]. 153

Obstructive jaundice due to malignant distal biliary obstruction can thus be relieved 154

by surgery or endoscopic metal or plastic stents [14, 15]. A number of randomized 155

controlled trials (RCTs) have compared various combinations of these interventions 156

[16, 17]. Endoscopic stents appear to offer a less invasive option, but the many 157

designs and stent types available have made selecting the ideal stent for individual 158


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patients complicated. This paper reviews the outcomes associated with surgery and 159

endoscopic therapies. 160

Objectives 161

The aim of the present study is to acquire and analyze data to compare success of 162

procedure, procedure-related complication, mortality in 30 days, and recurrent-163

jaundice rates in endoscopic surgical procedures in patients with distal biliary 164

obstruction due to periampullary tumors (i.e., pancreatic neoplasms or low bile duct 165

carcinoma). 166

167

MATERIALS AND METHODS 168

Protocol and Registration 169

PROSPERO 2015 CRD42015017792 [18] 170

Guidelines http://www.prisma-statement.org/statement.htm 171

Elegibility Criteria 172

a) Types of studies – Randomized clinical trials, controlled clinical trial, and cohort 173

studies. 174

b) Types of participants – Patients with distal biliary obstruction due to periampullary 175

tumors (i.e., pancreatic neoplasms or low bile duct carcinoma). 176

c) Types of intervention – Comparison between endoscopic palliative stents and 177

surgical palliative procedures. 178

d) Types of outcome measures – The main outcome measures were the following: 179

success of procedure, procedure-related complication, mortality in 30 days, and 180

recurrent-jaundice rates. 181

In this literature search, we do not limit ourselves by year of publication or by 182

language. 183

Information sources include MEDLINE as well as the Cochrane Controlled Trials 184

Register, EMBASE, EBSCO, LILACS, Library University of Sao Paulo, Research 185

website BVS, and SCOPE. 186

Search 187

Medline: 188


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P: “(Periampullary Tumors OR Biliary Tract Neoplasms OR Biliary Tract Cancer OR 189

Biliary tract tumors OR Bile Duct Cancer OR Pancreatic Neoplasms OR 190

Cholangiocarcinoma OR Pancreatic Carcinoma) AND 191

I: (Endoscopy OR Endoscopy, Gastrointestinal) AND 192

C: (Surgery OR Surgical Procedures, Operative)”. 193

Embase: 194

P: Pancreatic neoplasms OR bileduct neoplasms AND 195

I: endoscopy AND 196

C: surgery AND 197

('clinical trial' OR 'controlled study' OR 'major clinical study' OR 'prospective study' 198

OR 'retrospective study'))”. 199

Cochrane, LILACS, Scopus and CINAHL: 200

P: pancreatic neoplasms OR bileduct neoplasms AND 201

I: endoscopy AND 202

C: surgery 203

Study Selection 204

Eligibility assessment was performed independently in an unblinded, standardized 205

manner by 2 reviewers. Assessment included a thorough reading of the abstract to 206

identify studies that compare endoscopic with surgical techniques. Studies selected 207

were read in their entirety and excluded according criteria JADAD [19], 208

NEWCASTLE OTTAWA [20] and Mehodology Check List SIGN [21]. Studies that did 209

not report the results in absolute numbers and those not written in English, Spanish, 210

or Portuguese were excluded. Disagreements between reviewers were resolved by 211

consensus. 212

Data Collection Process and Items 213

We extracted data by a detailed reading of the results of each study. This included 214

information on the success of the procedure, procedure-related complication, 215

mortality in 30 days, and recurrent-jaundice rates. We only included absolute 216

numbers reported in the text of the article or with the analysis of graphs. We 217

excluded an article for not reporting the results in absolute numbers. One review 218

author extracted the following data from included studies, and the second author 219


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checked the extracted data. Disagreements were resolved by discussion between 220

the two reviewers; we did not contact authors for further information. 221

Data items 222

The following information was extracted from each included study: Characteristics of 223

population (type and location of tumors); type of intervention, considering different 224

modalities of techniques in endoscopic treatment (plastic stents, metallic stents, 225

covered or uncovered stents) versus surgical approach (hepaticojejunostomy, 226

cholecistojejunostomy, choledocojejunostomy and gastrojejunostomy associated); 227

type of outcome measure including complications, success of procedure, morbidity, 228

mortality, survival in 30 days, recurrent-jaundice, and hospitalization rates. 229

Risk of Bias In Individual Studies 230

Since both cohort and randomized studies were included, the risk of bias in 231

individual studies was assessed using the Newcastle-Ottawa Quality Assessment for 232

cohort studies [20] and JADAD Scale for randomized trials [19] as well as the 233

Mehodology Check List: SIGN for both [21,22]. 234

We extracted data into a table of all studies with the identification of all potential bias 235

of each study. Then, different factors were identified as individual generators of 236

biases, including age, comorbidities, techniques used, prevalence, and experience 237

(see Table 2). 238

Summary Measures 239

Individual analysis for each study included the following: experiment events rate 240

(EER), control event rate (CER), number needed to treat (NNT), and absolute risk 241

(ARR). 242

Synthesis of Results 243

We performed a meta-analysis with the software RevMan5 [23] using the following 244

characteristics: dichotomous data type, statistical method of Mantel-Haenszel, fixed 245

effect model analysis, effect measure risk difference, study confidence interval 95%, 246

total confidence interval 95%, and year of study. 247

Risk of bias across studies . 248

To identify true heterogeneity and cause for publication bias between studies, we 249

conducted both a graphic funnel plot and a I2 analysis. We noted a value of I2 250

greater than 50% as having high heterogeneity. If the study was outside the funnel 251


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plot it was regarded as publication bias, but if it was inside the funnel plot it was 252

considered as having true heterogeneity. 253

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RESULTS 255

Study Selection 256

We identified 8238 studies through MEDLINE, We identified 1941 studies through 257

COCHRANE, LILACS, SCOPUS, and CINAHL. Eliminating repeated studies, we 258

found 9179 studies in total. We excluded studies that did not have information about 259

periampullary cancers. We chose 8 studies that we reviewed with JADAD [19], 260

NEWCASTLE OTTAWA [20], and the Mehodology Check List: Cohort and Clinical 261

Trial studies SIGN [21]. We excluded a study that was written in French. We 262

included 7 studies for qualitative analysis and 5 studies for quantitative analysis (see 263

fig 1). 264

Study Characteristics 265

The characteristics of the studies are summarized in Table 3. Table 3 describes the 266

oncologic diagnosis analyzed, the number of interventions for each treatment group, 267

and the report in absolute numbers for each outcome of interest extracted. The 268

survival and hospital stay was expressed in mean without standard error, was no 269

topic under analysis. (See Table 1). 270

Risk of Bias Within Studies 271

We identify biases selected for qualitative analysis studies and evaluate them 272

according criteria from the JADAD, Mehodology Check List: SIGN, and 273

NEWCASTLE OTTAWA [19, 20, 21] (see Table 2). 274

Summary Measures 275

Individual analysis for each study included the following: experiment events rate 276

(EER), control event rate (CER), number needed to treat (NNT), and absolute risk 277

(ARR) (see Annex 1). 278

Results of Individual Studies and Synthesis of Resu lts 279

Procedure Success 280

Fig 2. Risk Difference in procedure success. 281

Procedure success: five clinical trial reported procedure success, and the 282

heterogeneity test indicated a χ2 of 4.09 and a I2 of 2%, demonstrating low 283


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heterogeneity. The fixed-effects model was adopted, and the RD was 0.02 (95 % CI: 284

-0.04, 0.07) (Fig. 2). Analysis of the pooled data revealed no statistically significant 285

differences in procedure success between the two therapies. 286

Mortality associated with procedure 287

Fig 3a. Risk difference in mortality associated with procedure for endoscopy and 288

surgery therapies. 289

Mortality associated with procedure: two clinical trials reported mortality associated 290

with procedure, and the heterogeneity test indicated a χ2 of 2.57 and a I2 of 61%, 291

demonstrating high heterogeneity. The fixed-effects model was adopted, and the risk 292

difference was -0.10 (95 % CI: -0.16, –0.03) (Fig. 3a). Analysis of the pooled data 293

revealed differences in mortality associated with procedure with significant risk of 294

bias. The funnel plot analysis identified true heterogeneity, and by consensus of 295

reviewers we opted to perform the meta-analysis using the risk ratio. 296

Fig 3b. Risk ratio in mortality associated with procedure for endoscopy and surgery 297

therapies. 298

Mortality associated with procedure: two clinical trials reported mortality associated 299

with procedure; the heterogeneity test was not applicable. The fixed-effects model 300

was adopted, and the risk ratio was 0.21 (95 % CI: -0.16, –0.03) (Fig. 3a). Analysis 301

of the pooled data revealed differences in mortality associated with procedure that 302

favored endoscopy therapy, with potential bias in this statement. 303

Mortality 30 Days 304

(Fig. 4) Risk Difference in mortality 30 days. 305

Mortality at 30 days: Five clinical trials reported mortality at 30 days; the 306

heterogeneity test indicated a χ2 of 1.44 and a I2 of 0%, demonstrating 307

homogeneity. The fixed-effects model was adopted, and the RD was -0.07 (95 % CI: 308

-0.13, 0.00) (Fig. 2). Analysis of the pooled data revealed statistically significant 309

differences in mortality at 30 days between the two therapies and favors endoscopy 310

therapy. 311

Complication associated with procedure 312

Fig 5a. Risk difference in complication associated with procedure for endoscopy and 313



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Complication associated with procedure: five clinical trials reported complication 315

associated with procedure; the heterogeneity test indicated a χ2 of 12.10 and a I2 of 316

67%, demonstrating high heterogeneity. The fixed-effects model was adopted, and 317

the RD was -0.19 (95 % CI: -0.28, –0.09) (Fig. 5a). Analysis of the pooled data 318

revealed differences mortality associated with procedure, with potential bias in this 319

statement. In the funnel plot analysis, the study Andersen (1999) was identified as a 320

source of heterogeneity for publication bias. By consensus of reviewers, we opted to 321

withdraw this work from the meta-analysis complication associated with procedure 322

(Fig 5b). 323

Fig 5b. Risk difference in complication associated with procedure for endoscopy and 324


Complication associated with procedure for endoscopy and surgery therapies: three 326

studies reported complication associated with procedure; the heterogeneity test 327

indicated a χ2 of 3.50 and an I2 of 14%, demonstrating low heterogeneity. The fixed-328

effects model was adopted, and the RD was -0.24 (95 % CI: -0.34, –0.24) (Fig. 5b). 329

Analysis of the pooled data revealed statistically significant differences in 330

complication associated with procedure and showed better outcomes for endoscopy 331

therapy. 332

Recurrent-Jaundice 333

(Fig. 6a) Risk difference in Recurrent-Jaundice 334

Recurrent-Jaundice: four clinical trials reported Recurrent-Jaundice; the 335

heterogeneity test indicated a χ2 of 22.53 and an I2 of 87%, demonstrating high 336

heterogeneity. The fixed-effects model was adopted, and the RD was 0.25 (95 % CI: 337

0.18, 0.32) (Fig. 6a). Analysis of the pooled data revealed differences for Recurrent-338

Jaundice with significant risk of bias in does this affirmation. In the funnel plot 339

analysis, the study Andersen (1989) was identified as a source of heterogeneity for 340

publication bias. By consensus of reviewers, we opted to withdraw this work from the 341

meta-analysis of Recurrent-Jaundice (Fig 6b). 342

Fig 6b. Risk difference in Recurrent-Jaundice for endoscopy and surgery therapies. 343

Recurrent-Jaundice for endoscopy and surgery therapies: three clinical trials 344

reported Recurrent-Jaundice; the heterogeneity test indicated a χ2 of 1.47 and an I2 345

of 0%, demonstrating homogeneity. The fixed-effects model was adopted, and the 346


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RD was 0.30 (95 % CI: 0.22, 0.38) (Fig. 6b). Analysis of the pooled data revealed 347

statistically significant differences for Recurrent-Jaundice and showed better 348

outcomes for surgery therapy. 349

Risk of Bias Across Studies 350

Although the results of success of the procedure were homogeneous between the 351

studies, and no difference was found between the procedures in clinical trials, there 352

is substantial risk of bias because the concept of success is different for each study. 353

Although all are based on a percentage of reduction of billirubin, the percentages 354

that determined a successful procedure were different. 355

Mortality at 30 days was homogeneous between the studies, and statistically 356

significant differences were found between the two therapies that favored endoscopy 357

therapy. We believe this result is one of the most solid because it was exposed in all 358

studies in absolute numbers and because the concept of death is unlikely subject to 359

interpretation bias. 360

With regard to complication associated with procedure, Andersen (1999) was 361

identified as a source of heterogeneity for publication bias. Excluding this study, we 362

analyzed four studies demonstrating low heterogeneity and found statistically 363

significant differences (with low probability of bias) in complication associated with 364

procedure that showed better outcomes for endoscopy therapy. 365

With regard to Recurrent-Jaundice, Andersen (1999) was identified as a source of 366

heterogeneity for publication bias. Excluding this study, we analyzed four studies 367

demonstrating homogeneity and revealed statistically significant differences (with low 368

probability of bias) in Recurrent-Jaundice analysis that showed better outcomes for 369

surgery therapy. 370

371

DISCUSSION 372

Summary of Evidence 373

About 70% of patients with periampullary tumors have evidence of obstructive 374

jaundice at the time of presentation. Therefore, the main goal of palliative therapy in 375

those patients is to resolve the biliary obstruction. Five randomized controlled trials 376

comparing the outcomes of endoscopic stent placement versus surgical bypass for 377

palliation therapy was analyzed. 378


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No statistically significant differences were found in procedure success between the 379

two therapies. Differences were found between mortality associated with procedure 380

that favored the endoscopy therapy. There was significant risk of bias in this 381

affirmation, and the risk ratio was 0.21. Statistically significant differences (NNT 14) 382

in mortality at 30 days between the two therapies favors endoscopy therapy. This is 383

perhaps the most striking result unidentified in previous reviews. Also, statistically 384

significant differences (NNT 4) in complication associated with procedure between 385

the two therapies favors endoscopy therapy. Finally, statistically significant 386

differences (NNH 3) were found for Recurrent-Jaundice and showed better 387

outcomes for surgery therapy. 388

389

LIMITATIONS 390

Several limitations of the present study need to be considered. The characteristics of 391

patients were not comparable in some studies. Although the studies were 392

homogeneous in age, some studies had different average ages, which may lead to a 393

significant bias in the results. Several endoscopic therapies including plastic stent 394

and metallic stent (covered or uncovered) were used, and may be bias generator. 395

The type of operation used was also different in all studies and may cause some 396

biases. Finally, publication bias might exist when including published studies 397

because positive results are more likely to be published than negative results. 398

399

CONCLUSION 400

Endoscopic palliative drainage is associated with a lower rate of complication as well 401

as mortality associated with procedure and mortality within 30 days. Recurrent-402

jaundice analysis demonstrated an overall lower rate in surgical bypass procedures. 403

404

CONFLICT OF INTEREST 405

Declare any financial interest or any conflict of interest exists. 406

407

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AUTHOR’S CONTRIBUTIONS 411

Silvia Lucia Alves de Lima, 412

Group1 - Conception and design, Acquisition of data, Analysis and interpretation of 413

data 414

Group 2 - Drafting the article, Critical revision of the article 415

Group 3 - Final approval of the version to be published 416

Fabio Alberto Castillo Bustamante, 417


data 419



Eduardo Guimarães Hourneaux de Moura, 422

Group 1 - Conception and design, Acquisition of data, Analysis and interpretation of 423

data 424



Wanderley Bernardo Marques, 427


data 429



Everson Luiz de Almeida Artifon, 432


Dalton Marques Chaves, 434


Tomazo Antonio Prince Franzini, 436


Carlos Kiyoshi Furuya Junior, 438


440

ACKNOWLEDGEMENTS 441

NIL 442


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trial of endoscopic endoprosthesis versus operative bypass in malignant 522

obstructive jaundice." Gut, 1989 Aug: 30(8):1132-5. . 523

28. Shepherd HA1, Royle G, Ross AP, Diba A, Arthur M, Colin-Jones D. 524

"Endoscopic biliary endoprosthesis in the palliation of malignant obstruction of 525

the distal common bile duct: a randomized trial." Br J Surg, 1988 Dec: 526

75(12):1166-8. 527

29. Tobias, Philippus C. Bornman E. "prospective controlled trial of transhepatic 528

biliary endoprosthesis versus bypass surgery for incurable carcinoma of head 529

of pancreas." surgical gastroenterology unit, gastrointestinal clinic, 1986: 69-530

71. 531

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TABLES 538

Table 1: Study Characteristics. 539

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Table 2: Risk of blas within studies. 551

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FIGURE LEGENDS 564

Figure 1: Flow Diagram. 565

Figure 2: Risk Difference in procedure success. 566

Figure 3: (a) Risk difference in mortality associated with procedure for endoscopy 567

and surgery therapies. (b) Risk ratio in mortality associated with procedure for 568

endoscopy and surgery therapies. 569

Figure 4: Risk Difference in mortality 30 days. 570

Figure 5: (a) Risk difference in complication associated with procedure for 571

endoscopy and surgery therapies. (b) Risk difference in complication associated with 572

procedure for endoscopy and surgery therapies. 573

Figure 6: (a) Risk difference in Recurrent-Jaundice. (b) Risk difference in Recurrent-574

Jaundice for endoscopy and surgery therapies. 575

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FIGURES 596

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Figure 1: Flow Diagram. 598

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600

Figure 2: Risk Difference in procedure success. 601

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a 612 613 b 614

b 615

Figure 3: (a) Risk difference in mortality associated with procedure for endoscopy 616

and surgery therapies. (b) Risk ratio in mortality associated with procedure for 617

endoscopy and surgery therapies. 618

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Figure 4: Risk Difference in mortality 30 days. 621


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a 622

623

b 624

Figure 5: (a) Risk difference in complication associated with procedure for 625

endoscopy and surgery therapies. (b) Risk difference in complication associated with 626

procedure for endoscopy and surgery therapies. 627

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a 633

b 634

Figure 6: (a) Risk difference in Recurrent-Jaundice. (b) Risk difference in Recurrent-635

Jaundice for endoscopy and surgery therapies. 636

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Annex 1: 653

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Journal Name: International Journal of Hepatobiliary and … · 2018-12-07 · 8 Hourneaux de Moura...

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