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Manuscript Accepted | Early View Article

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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: Biliary ascariasis in the etiology of recurrent pyogenic cholangitis in an endemic area

Authors: Mohammad S Khuroo, Naira S Khuroo, Mehnaaz S Khuroo

doi: To be assigned

Early view version published: 22nd January 2015

How to cite the article: Khuroo MS, Khuroo NS, Khuroo MS. Biliary ascariasis in the etiology of recurrent pyogenic cholangitis in an endemic area. 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: Biliary ascariasis in the etiology of recurrent pyogenic cholangitis in an 3

endemic area 4

5

AUTHORS: 6

Mohammad S Khuroo1, Naira S Khuroo2, Mehnaaz S Khuroo3 7

8

AFFILIATIONS: 9

1MBBS, MD, DM, FACP, FRCP, MACP; Director & Consultant Gastroenterology, Dr. 10

Khuroo’s Medical Clinic, Srinagar, Kashmir, India. 11

2MBBS, FMIR (KFSH & RC, Riyadh); Consultant Radiologist, Dr. Khuroo’s Medical 12

Clinic, Srinagar, Kashmir, India. 13

3MD, Assistant Professor, Department of Pathology, Government Medical College, 14

Srinagar, Kashmir, India. 15

16

CORRESPONDING AUTHOR DETAILS 17

Prof. Mohammad Sultan Khuroo, MD, DM, FACP, FRCP, MACP, 18

Dr. Khuroo’s Medical Clinic, Sector 1, Sher-e-Kashmir Colony, Qamarwari, Srinagar, 19

Kashmir, J&K 190010, India. 20

Email ID: [email protected] 21

22

Short Running Title: Biliary ascariasis and recurrent pyogenic cholangitis 23

24

Guarantor of Submission : The corresponding author is the guarantor of 25

submission. 26

27

28

29

30

31


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endemic area 33

34

ABSTRACT 35

Aims: 36

The role of biliary ascariasis in etiology of recurrent pyogenic cholangitis in endemic 37

areas has not been well studied. 38

39

Methods: 40

We studied 30 patients of recurrent pyogenic cholangitis with brown pigment stones 41

and 30 patients with cholesterol gallstones. Stones from 22 patients (11 brown 42

pigment stones and 11 gallstones) were examined by infrared spectrophotometry to 43

substantiate the classification of stones done on visual inspection. Biliary calculi 44

were considered to be associated with Ascaris lumbricoides in those with: previous 45

documented evidence of biliary ascariasis, bile specimens containing ova of Ascaris 46

lumbricoides on light microscopy and worms, worm fragments or their ova forming 47

the nidus of stones on histological examination. 48

49

Results: 50

Bile cultures grew microorganisms in 24 (80%) patients with recurrent pyogenic 51

cholangitis while only one patient with gallstones grew Escherichia coli from bile. 52

None of the patients in either group had past or persisting evidence of clonorchiasis. 53

Five patients had previous documentation of biliary ascariasis. In three patients bile 54

contained ova of Ascaris lumbricoides and stones in 22 patients contained worm, 55

worm fragments or their ova on histological examination. Overall 24 (80%) patients 56

with recurrent pyogenic cholangitis had past or persistent evidence of biliary 57

ascariasis while only one patient with gallstones had worm fragments on 58

histopathology of stones (p<0.001). 59

60

61

62

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Conclusion: 64

We conclude that in endemic areas bacterial infection of the bile ducts in recurrent 65

pyogenic cholangitis occurs with biliary invasion by Ascaris lumbricoides and dead 66

worms, their fragments or ova form nidus of brown pigment stones formation in such 67

patients. 68

69

Keywords: Ascaris lumbricoides, Biliary ascariasis, Recurrent pyogenic cholangitis, 70

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endemic area 96

97

INTRODUCTION 98

Recurrent pyogenic cholangitis (RPC) is a disease characterised by chronic infection 99

and stone formation in the bile ducts [1]. It mainly affects inhabitants of Southeast 100

Asia and is most prevalent in Taiwan and the south of China. In Hong Kong it is most 101

common disease of the biliary tract and the third most frequent cause of acute 102

abdominal pain requiring surgical intervention. The disease has also been reported 103

from Indonesia, Japan, Singapore, Malaysia, South Africa and Chinese Immigrants 104

in Canada [2-9]. In Kashmir, India, RPC constitutes 12.5% of all patients with biliary 105

disease [10]. This unusual biliary tract syndrome is now being encountered with 106

increased frequency in Western societies especially in the United States, largely as a 107

result of increased immigration of refugees from Asia during and after the Vietnam 108

War [11-13]. 109

The clinical presentation of patients with RPC is characteristic. Majority of patients 110

present with recurrent right upper quadrant pain, nausea and vomiting, often 111

accompanied by fever, shaking chills and jaundice [2]. The intrahepatic and 112

extrahepatic ducts are dilated and contain soft brown pigment stones, biliary mud 113

and/ or pus. The gall bladder is involved in only 15% of patients. As a result of 114

recurrent cholangitis and stone formation, bile ducts develop strictures, excessive 115

branching and arrowhead formation of the intrahepatic branches [14]. Bile cultures 116

invariably yield Escherichia coli, or other colonic aerobic flora [2, 10, 11]. Secondary 117

changes in liver biopsy are characteristic of obstruction and cholangitis [15]. Portions 118

of the liver may atrophy as a result of long standing obstruction. If infection gets the 119

upper hand intrahepatic abscess formation and septicaemia may supervene [2]. 120

Although RPC has been recognised for over half a century, its exact 121

etiopathogenesis has remained unknown [16]. The major controversy is on the route 122

of infection in to the bile ducts. The popular hypothesis include: a) portal 123

bacteraemia leading to portal phlebitis which secondarily spreads to ductal system 124

[15]; (b) invasion of bile ducts by parasites, viz. Ascaris lumbricoides and Clonorchis 125

sinensis, which carry enteric organisms along with into the bile ducts [4, 11, 17, 18]. 126


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Ascaris lumbricoides is highly endemic and Clonorchis sinensis infection is not 127

known to occur in Kashmir, India; this made us to suspect an association between 128

biliary ascariasis and recurrent pyogenic cholangitis. In the present study, we looked 129

for evidence of past or persisting biliary invasion by Ascaris lumbricoides in patients 130

with RPC and compared it with those of cholesterol gall stones. 131

132

MATERIALS AND METHODS 133

The study group included 30 consecutive patients with RPC. 30 patients with 134

cholesterol gall stones, age and sex matched with the study group, formed the 135

control group. 136

Diagnostic Criteria . The diagnosis of RPC was made on the basis of the following 137

criteria [14, 19]. (a) recurrent (more than 3 attacks) of right upper abdominal pain, 138

fever , rigors and jaundice (b) elevated serum alkaline phosphatase levels more than 139

twice the upper limit of normal (normal values 1.63 to 4.65 microkat/l) (c) 140

cholangiographic abnormalities viz. dilatation, strictures, excessive branching and 141

arrowhead formation of intrahepatic bile ducts; (d) soft brown pigment stones in the 142

hepatic ducts and /or common bile duct, but selectively sparing the gall bladder; (e) 143

stones containing calcium bilirubinate as a principal component [20]. The following 144

groups of patients with cholangitis were excluded from the study: (a) patients with 145

cholelithiasis with choledocholithiasis; (b) patients with Choledocholithiasis following 146

previous cholecystectomy (c) patients with bile duct strictures or injury after previous 147

biliary surgery (d) patients with biliary and pancreatic neoplasm; (e) patients with 148

biliary ascariasis or hydatidosis; (f) patients who were found to have cholesterol or 149

black pigment stones at surgical exploration or endoscopic spincterotomy. 150

Patients were diagnosed to have cholesterol gall stones on the basis of following 151

criteria [16, 21]: (a) stones located in gallbladder; (b) on visual inspection stones of 152

cholesterol type. Following criteria were considered as evidence of past or persisting 153

Ascaris invasion of the biliary tree: (a) delineation of adult Ascaris in the biliary tree 154

by imaging techniques or their recovery at surgery done more than 2 years prior to 155

the diagnosis of RPC; (b) bile specimen on light microscopy containing ova of 156

Ascaris lumbricoides; (c) histological examination showing worm, worm fragments or 157

ova forming the nidus of stones. 158


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Bile specimens were collected at laparotomy by direct puncture of common bile duct 159

or by a cannula passed into common bile duct through the cystic duct. Bile was 160

cultured for aerobic and anaerobic organisms by established methods [22]. An 161

aliquot of bile was centrifuged and examined under light microscopy for ova of 162

Ascaris lumbricoides and Clonorchis sinensis [2]. Each stone obtained at 163

laparotomy was washed with deionised distilled water until supernatant became 164

clear, was split carefully into two so as not to damage the broken surface; and its 165

appearance and structure of the nucleus, interior and surface areas were inspected 166

[23]. On visual inspection gallstones were classified as cholesterol stones, brown 167

pigment stones and black pigment stones on the basis of criteria reported previously 168

[24]. 169

Afterwards, stones were sliced with a knife and fixed in 10% formal saline, 170

dehydrated, cleared and embedded in paraffin wax. Serial sections were cut and 171

stained with hematoxylin and eosin, PAS-Alcian blue pH 2.5, Masson’s trichrome 172

and orcein. Multiple sections were examined for worm or worm fragments and 173

classified as adult worms, cuticle and ova. Ascaris lumbricoides and Clonorchis 174

sinensis were recognised on the basis of characteristic worm appearance, cuticular 175

morphology and ova characteristics [25]. 176

Stones from 22 patients (11 brown pigment stones and 11 cholesterol stones) were 177

examined by chemical microscopy, infrared spectrophotometry, polarised light 178

microscopy and x-ray diffraction as reported earlier [20]. The data on various stone 179

components were included in this study to further substantiate the classification of 180

stones done on visual inspection. 181

Endoscopic retrograde-cholangiopancreatography (ERCP) was obtained using JFIT 182

side viewing duodenoscope. Cholangiograms were read by two experienced 183

personal without knowledge of the clinical details. Cholangiographic abnormalities 184

were reported as described elsewhere [14]. 185

The diagnosis of biliary ascariasis was made on characteristic sonographic and 186

cholangiographic appearance as described earlier [26, 27, 28]. 187

The study was approved by the ethical committees of Sher-e-Kashmir Institute of 188

Medical Sciences and Dr. Khuroo’s Medical Clinic and all the patients gave a written 189


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informed consent for the study. The values were expressed as mean ±1 SD. The two 190

groups were compared by Х2 with Yates correction. 191

192

RESULTS 193

Study group . Thirty patients (10 men and 20 women) with a mean age of 35.9±15.2 194

years constituted the study group. The mean duration of disease was 4.1±4.2 yr 195

(range 11 mo to 20 yr) and all had recurrent episodes of right upper quadrant pain, 196

fever with chills and jaundice. Stool analysis revealed ova of Ascaris lumbricoides in 197

all patients; however, none of the patients had ova of Clonorchis sinensis. Liver 198

function tests revealed mean serum bilirubin levels of 116.2±152.1 micro mol/l, 199

serum alkaline phosphatase 18.65± 12.18 microkat /l and mean serum alanine 200

aminotransferase level of 1.66±1.25 micro kat/l. In 24 patients bile samples grew 201

organisms on culture which included Escherichia coli in 12, Kleibsella aerogenosa in 202

10 and Streptococcus feacalis in 2 patients. Stones were located in the hepatic ducts 203

alone in 7 patients, hepatic ducts and common bile duct in 12 patients and in 204

common bile duct alone in 10 patients. None of these patients had stones inside the 205

gall bladder. Cholangiogram revealed biliary dilatation in all patients, excessive 206

branching of hepatic ducts in 15(50%) patients, strictures of common bile duct and / 207

or hepatic ducts in 16 (53%) patients and abrupt termination and arrowhead 208

formation of intrahepatic ducts in 12 (40%) patients. All patients had surgery, 209

choledechotomy and stone extraction form bile and hepatic ducts. Five patients with 210

disease of the left lobe had in addition left hepatic lobectomy. At laparotomy brown 211

pigment stones were recovered from bile ducts in all the patients. The number of 212

stones recovered from each patient varied from 1 to 10 (mean +SD 7±3) and the size 213

of stones varied from 0.5 cm to 2.5 cm (mean 1.1±0.9 cm). On cut sections, the 214

stones had a characteristic laminated appearance due to brownish yellow and 215

granular pigmented material. 216

Control group . Thirty patients with gall stones constituted the control group which 217

included 10 men and 20 women with mean age of 38.8±8.4 years and the mean 218

duration of disease from 11.7±17.9 mo (range 1 month to 8 yr). Of these, 27 patients 219

presented with recurrent biliary colic, 2 patients had suffered from acute cholecystitis 220

and one patient had an episode of acute cholangitis. Stool analysis revealed ova of 221


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Ascaris lumbricoides in 5 patients but ova of Clonorchis sinensis were not seen in 222

any of them. Liver function tests did not reveal any abnormality in serum bilirubin, 223

alkaline phosphatase or alanine aminotransferase. All the 30 patients had stones 224

inside the gall bladder and one patient, in addition, had a stone in the common bile 225

duct. Bile cultures were sterile in 29 patients while Escherichia coli were grown on 226

culture in one patient. On visual inspection, the stones were of cholesterol type in all 227

the 30 patients. 228

Biliary stone analysis was done in 22 patients including 11 patients each with 229

recurrent pyogenic cholangitis and gallstones. Cholesterol formed the major 230

component of gall stones while in brown pigment stones calcium bilirubinate was the 231

major component (Table 1). 232

None of the patients in the study or control group had evidence of past or persisting 233

infection of biliary tree by Clonorchis sinensis. 24 (80%) of the 30 patients in the 234

study group had evidence of either past and/ or persisting invasion of biliary tract by 235

Ascaris lumbricoides. In contrast only one patient with gall stones on histological 236

examination showed Ascaris cuticle forming the nidus of the stone (Table 2). Two 237

patients with previous documentation of biliary ascariasis had formed stones which 238

did not contain worm or worm fragments or ova on histological examination. 239

Five patients (2 men and 3 women) had evidence of biliary ascariasis 5.3±5.8 yr 240

(range 3 to 16 yr) prior to the diagnosis of recurrent pyogenic cholangitis and 241

development of bile duct stones. One patient had four episodes of biliary invasion by 242

Ascaris lumbricoides over 8 year period. The diagnosis of biliary ascariasis was 243

documented on sonography in one patient, ERCP in 3 patients (Figure 1), and at 244

laparotomy in one patient. 245

Bile specimens on light microscopy showed ova of Ascaris in 3 patients. These ova 246

were both fertilized and unfertilised and showed various stages of degeneration 247

(Figure 2). These three patients had previous biliary invasion by Ascarids more than 248

3 years prior to the diagnosis of recurrent pyogenic cholangitis. 249

Of the 22 patients with worm, worm fragments formed the nidus of the stones, 5 250

patients had adult Ascarids, 8 cuticle fragment and 9 ova of Ascaris lumbricoides in 251

the stone sections (Figure 3 & 4). 252

253


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DISCUSSION 254

The first National Institute of Health International workshop on pigment gallstones 255

classified all pigment stones and brown pigment stones and it was agreed that 256

pigment stones can be distinguished from cholesterol stones and between one 257

another by gross inspection [15]. Brown pigment stones located in the intrahepatic 258

and extrahepatic bile ducts are characteristic of recurrent pyogenic cholangitis and 259

calcium bilirubinate is the principal component of such stones. The biliary stones in 260

the study group in this report had all the characteristics of those reported in patients 261

with recurrent pyogenic cholangitis from the Orient. This was in contrast to stones in 262

the control group which were located in the gall bladder and cholesterol formed the 263

principal constituent of these stones. Brown pigment stones are associated with 264

bacterial infection of the bile ducts by Escherichia coli and other colonic aerobic flora. 265

These organisms produce high amounts of beta glucuronidase which causes 266

deconjugation of the bile pigments and their precipitation as stones [18, 22]. Low 267

protein diet leads to lower activity of glucaro 1,4 lactone which is a natural inhibitor of 268

beta glucuronidase and promotes stone formation in such patients [18]. 269

Although the role of bile duct infection in the pathogenesis of brown pigment stones 270

is well established, the route of infection into the biliary tree continues to be a matter 271

of debate. The popular theory that portal bacteraemia causing portal phlebitis 272

secondarily spreads to the ductal system is fraught with major criticism. The infection 273

having reached into the liver is excreted into the bile and it is generally agreed that 274

no serious consequences would ensue as long as there is free biliary drainage [4]. 275

Bockus considers that portal bacteraemia is harmless under ordinary circumstances 276

[29] and Wilkis also believes that bacteria excreted into the bile will not usually give 277

rise to infection [30]. Moreover, comparative studies in the West and Orient have 278

shown similar percentage of portal bacteraemia in surgical patients, yet recurrent 279

pyogenic cholangitis has not been reported from western countries [2]. This 280

hypothesis also fails to explain the special geographical distribution of recurrent 281

pyogenic cholangitis. 282

Many authors have postulated association of recurrent pyogenic cholangitis with 283

biliary infestation by Clonorchis sinensis and /or Ascaris lumbricoides. The 284

hypothesis is based upon geographical distribution of recurrent pyogenic cholangitis 285


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which resembles that of clonorchiasis and ascariasis. About half of the patients with 286

RPC are infected with Clonorchis sinensis and about 12.9% have evidence of biliary 287

ascariasis [14, 16, 19]. Ascaris lumbricoides and Clonorchis sinensis formed the 288

nidus of the stones in 38% and 19% patients of RPC respectively in a study from 289

Hong Kong [17]. In one study from South Africa on the role of ascariasis in non-290

western pattern of biliary stones, Ascaris Lumbricoides was delineated in the biliary 291

tree in 14 of the 15 patients [9]. However, many authors have casted doubt on such 292

an association and believe that RPC and biliary parasites are common in the regions 293

of world with low socioeconomic status and that their co-existence in the same 294

patient may be related to their high prevalence without any cause and effect 295

relationship. Up till, now there is no case control study available in literature which 296

studies the role of biliary parasites in a group of patients with brown pigment stones 297

and a control group with different type of stones. 298

Our data clearly speak of a strong association between biliary invasion by Ascaris 299

lumbricoides and recurrent pyogenic cholangitis. In contrast, age and sex matched 300

controls with cholesterol gall stones did not show such an association. In five 301

patients biliary invasion by round worms preceded the diagnosis of RPC by many 302

years. Previous data from Kashmir have shown that 12.6% of patients with biliary 303

ascariasis when followed for long time form brown pigment stones in the hepatic 304

ducts [10]. These data were strongly in favour of a causal relationship of biliary 305

ascariasis in recurrent pyogenic cholangitis. 306

The pathogenesis of bile duct infection and stone formation and stone formation in 307

patients of recurrent pyogenic cholangitis following biliary invasion by round worms is 308

multifactorial. Once Ascaris lumbricoides invades the biliary tree, it also carries along 309

with enteric organisms. It also causes partial obstruction of the bile ducts leading to 310

inadequate biliary drainage, bile stasis and establishment of infection in the biliary 311

tree. Recently we have shown that recurrent Ascaris invasion causes papillitis which 312

induces motor abnormalities resulting in delayed biliary drainage and recurrent 313

episodes of cholangitis [19]. Once the Ascaris invade the biliary tree, they usually 314

move out of the bile ducts as they are very agile and motile. Occasionally, however, 315

they may get trapped and die inside the bile ducts. Worm extracts contain high 316

activity of beta glucuronidase which facilitates deconjugation of bile pigments. Dead 317


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worms, ova and worm fragments act as a potential nidus for stone formation. Data 318

from the present study showed that 22 of the 30 stones analysed contained worms, 319

worm fragments or their ova as the nidus of stones. Maki in 1965 showed in vitro 320

studies with remarkable precipitation of calcium bilirubinate on to the surface of 321

Ascaris eggs that were incubated in human bile [18]. 322

The present study was done in an endemic area of ascariasis. Clonorchis Sinensis 323

has not been reported from Kashmir. It is, however, prevalent in many countries of 324

South East Asia from where RPC has been reported. In these countries, the 325

association of Clonorchis sinensis with recurrent pyogenic cholangitis has been 326

established. About half of the patients with RPC in these countries are infected with 327

this parasites and about 16% of brown pigment stones in these patients contained 328

ova of Clonorchis Sinensis [17]. Clonorchis sinensis migrates from duodenum into 329

the biliary tree where it takes permanent residence. It causes desquamation of the 330

bile epithelium, hyperplasia and stone formation [2]. 331

332

CONCLUSION 333

We conclude that in endemic areas bacterial infection of the bile ducts in recurrent 334

pyogenic cholangitis occurs with biliary invasion by Ascaris lumbricoides and dead 335

worms, their fragments or ova form nidus of brown pigment stones formation in such 336

patients. However, our hypothesis of association between biliary ascariasis and RPC 337

needs to be substantiated by exact mechanism of stone formation. The rate of worm 338

infestation in our population is very high (26). The best form of prevention is to keep 339

the gut free of worms and to prevent, re-infestation by improving hygienic methods 340

and regular three monthly courses of anthelmintic therapy. The clinicians should be 341

aware of relationship between biliary ascariasis and RPC and apply this knowledge 342

in routine clinical practice. 343

344

CONFLICT OF INTEREST 345

The authors declare no conflict of interest in submission of the manuscript 346

347

348

349


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AUTHOR’S CONTRIBUTIONS 350

Khuroo Mohammad Sultan 351

Group 1: Substantial contribution to concept, design, acquisition and analysis of data 352

and interpretation of data 353

Group 2: Drafting of article, revising critically for intellectual content 354

Group 3: final approval of the version to be published 355

Khuroo Naira Sultan 356

Group 1: Substantial contribution to concept, design, acquisition of data 357

Group 2: Drafting of article 358

Group 3: Final approval of the version to be published 359

Khuroo Mehnaaz Sultan 360

Group 1: Substantial contribution to concept, design, analysis and interpretation of 361

data 362

Group 2: Drafting of article, revising critically for intellectual content 363

Group 3: Final approval of the version to be published 364

365

ACKNOWLEDGEMENTS 366

NIL 367

368

REFERENCES 369

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5. Chang TM, Passaro E. Intrahepatic stones: The Taiwan experience. Am J 378

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AJR 1974; 122:368-74. 384

9. Schulman A. Non-western patterns of biliary stones and the role of biliary 385

ascariasis. Radiology 1989; 162:425-30. 386

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Wittich GR, et al. Oriental Cholangiohepatitis: Diagnostic imaging and 393

interventional management. AJR 1986; 146:327-31. 394

13. Federle MP, Cello JP, Laing FC, Jeffery RB. Recurrent pyogenic 395

cholangitis in Asian immigrants. Use of ultrasonography, computed 396

tomography and cholangiography. Radiology 1982; 143:151-56. 397

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cholangitis: A study by endoscopic retrograde cholangiography. 399

Gastroenterology 1978; 74:1196-1203. 400

15. Trotman BW, Soloway RD. Pigment gallstone disease: Summary of the 401

National Institute of Health – International workshop. Hepatology 1982; 402

2:879-84. 403

16. Way LW, Sleisenger MH. Biliary obstruction, cholangitis and 404

Choledocholithiasis. In: Sleisenger MH, Fordtran JS, eds. Gastrointestinal 405

disease. Philadelphia: WB Saunders 1983; 1389-1403. 406

17. Tech TB. A study of gallstones and included worms in recurrent pyogenic 407

cholangitis. J Path Bact 1963; 86:123-29. 408

18. Maki T. Pathogenesis of calcium bilirubinate gall stone: Role of E. Coli, 409

beta glucuronidase and coagulation by inorganic ions, polyelectrolyte’s 410

and agitation. Annals of Surg 1966; 164:90-100. 411


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19. Khuroo MS, Zargar SA, Yattoo GN, Allai MS, Khan BA, Dar MY, Boda MI, 412

et al. Oddi’s sphincter Motor activity in patients with Recurrent Pyogenic 413

cholangitis. Hepatology. 1993; 17(1):53-8. 414

20. Rustgi VK, Khuroo MS. Biliary stone analysis in recurrent pyogenic 415

cholangitis. [Abstract] Hepatology 1993. 416

21. Soloway RD, Trotman BW, Ostrow JD. Pigment gallstones. 417

Gastroenterology 1977; 72:167-82. 418

22. Cetta FM. Bile infection documented as initial event in the pathogenesis of 419

brown pigment biliary stones. Hepatology 1986; 6:482-89. 420

23. Trotman BW, Morris TA III, Sanchez HM, Soloway RD, Ostrow JD. 421

Pigment versus cholesterol cholelithiasis: Identification and quantification 422

by infrared spectroscopy. Gastroenterology 1977; 72:495-98. 423

24. Trotman BW, Ostrow JD, Solway RD. Pigment vs. cholesterol 424

cholelithiasis. Comparison of stones and bile composition. Am J Dig Dis 425

1974; 19:585-90. 426

25. Khuroo MS, Dar MY, Yattoo GN, Khan BA, Boda MI, Zargar SA, Javid G, 427

Allai MS: Serial Cholangiographic Appearances in Recurrent Pyogenic 428

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26. Khuroo MS and Zargar SA. Biliary ascariasis: A common cause of biliary 430

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88:418-23. 432

27. Khuroo MS, Zargar SA, Mahajan R, Bhat RL, Javid G. Sonographic 433

appearances in biliary ascariasis. Gastroenterology 1987; 93:267-72. 434

28. Khuroo MS, Zargar SA, Mahajan R. Hepatobiliary and pancreatic 435

ascariasis in India. Lancet.1990; 335:1503-06. 436

29. Bockus HL. Gastroenterology, Philadelphia W.B. Saunders Company, 437

1946; 3:672. 438

30. Wilkis AL. The bacteriology of cholecystitis. Brit. J Surg 1928; 15:450. 439

440

441

442

443


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TABLES 444

Table 1: Data on stone analysis showing various components in 11 brown pigment 445

stones and 11 gall stones. 446

No. Component Brown pigment

stones(%± S.D)

Gall stones (± S.D)

1 Cholesterol 21.27±13.75 92.25±4.0

2 Calcium Bilirubinate 62.7±19.2 4.25±2.1

3 Calcium Carbonate - 0.8±1.3

4 Mixed bile pigments 15.9±12.2 1.6±1.7

5 Calcium salts of fatty acids 3.0±2.0 1.0

447

448

Table 2: Data showing evidence of biliary invasion by Ascaris lumbricoides in study 449

and control group. 450

Evidence of biliary

invasion by Ascaris

Recurrent pyogenic

cholangitis (n=30)

Gall stones

(n=30)

P value

Previous

Hepatobiliary

ascariasis

5* 0

>0.05

Bile positive for ova

of Ascaris

lumbricoides

3 0 >0.20

Stones Positive for

Ascaris lumbricoides

22 1 <0.001

Total 24 1 <0.001

*3 patients had stones positive for Ascaris while in 2 patients, stones did not contain 451

Ascaris on histological sections. 452

453

454

455

456

457


of 21

FIGURE LEGENDS 458

Figure 1: Recurrent pyogenic cholangitis. 30 year female with recurrent attacks of 459

cholangitis for 6 months presented with severe pyogenic cholangitis and septic 460

shock. She was admitted to intensive care unit and had emergency ERCP and 461

endoscopic naso-biliary drainage. This patient was diagnosed with biliary ascariasis 462

5 year prior to this episode of cholangitis. Panel (a) shows ERCP Cholangiogram 463

obtained 5 year prior to present admission revealing two long linear smooth filling 464

defect in the common and left hepatic duct (arrows). Panel (b) shows ERCP 465

cholangiogram performed during present admission. Cholangiogram revealed biliary 466

dilatation with multiple filling defects and cholangitic changes in the common hepatic, 467

right and left hepatic duct. Naso-biliary tube is in place to treat pyogenic cholangitis. 468

Figure 2: Microscopy of bile sample obtained from a patient with recurrent pyogenic 469

cholangitis showing fertilized (panel a) and unfertilized (panel b) ova of Ascaris 470

lumbricoides. 471

Figure 3: Recurrent pyogenic cholangitis. 36 year female presented with acute 472

pyogenic cholangitis and septic shock. Panel (a): ERCP cholangiogram showing 473

gross dilation of left hepatic ductal system packed with stones and sludge, dilation of 474

common duct with stones and minimal cholangitis changes in the right ductal 475

system. Panel (b): Photograph of left hepatectomy specimen showing gross hepatic 476

duct changes with multiple brown pigment stones. Panel (c): Histological section of a 477

brown pigment stone recovered showing multiple linear worm fragments containing 478

large number of ova of Ascaris lumbricoides and encrusted with mineral deposits 479

(Masson’s trichome x100). 480

Figure 4: Recurrent pyogenic cholangitis. A 16 female presented with recurrent 481

episodes of abdominal pain, fever and jaundice for last many years. Panel (a): ERCP 482

cholangiogram shows marked dilation, elongation and arrow head appearance of left 483

hepatic ductal system with numerous filling defects. Panel (b): Photograph of left 484

hepatectomy specimen showing extensive dilation and destruction of left hepatic 485

ductal system with numerous brown pigment stones. Panel (c): Photograph of soft 486

brown pigment stone. Panel (d): Histological section of a brown pigment stone 487

recovered showing multiple worm segments containing large number of ova of 488

Ascaris lumbricoides encrusted with mineral deposits (Masson’s trichome x100). 489


of 21

FIGURES 490

491

Figure 1: Recurrent pyogenic cholangitis. 30 year female with recurrent attacks of 492

cholangitis for 6 months presented with severe pyogenic cholangitis and septic 493

shock. She was admitted to intensive care unit and had emergency ERCP and 494

endoscopic naso-biliary drainage. This patient was diagnosed with biliary ascariasis 495

5 year prior to this episode of cholangitis. Panel (a) shows ERCP Cholangiogram 496

obtained 5 year prior to present admission revealing two long linear smooth filling 497

defect in the common and left hepatic duct (arrows). Panel (b) shows ERCP 498

cholangiogram performed during present admission. Cholangiogram revealed biliary 499

dilatation with multiple filling defects and cholangitic changes in the common hepatic, 500

right and left hepatic duct. Naso-biliary tube is in place to treat pyogenic cholangitis. 501

502

503


of 21

504

Figure 2: Microscopy of bile sample obtained from a patient with recurrent pyogenic 505

cholangitis showing fertilized (panel a) and unfertilized (panel b) ova of Ascaris 506

lumbricoides. 507

508

509

510

511

512

513

514

515

516


of 21

517

Figure 3: Recurrent pyogenic cholangitis. 36 year female presented with acute 518

pyogenic cholangitis and septic shock. Panel (a): ERCP cholangiogram showing 519

gross dilation of left hepatic ductal system packed with stones and sludge, dilation of 520

common duct with stones and minimal cholangitis changes in the right ductal 521

system. Panel (b): Photograph of left hepatectomy specimen showing gross hepatic 522

duct changes with multiple brown pigment stones. Panel (c): Histological section of a 523

brown pigment stone recovered showing multiple linear worm fragments containing 524

large number of ova of Ascaris lumbricoides and encrusted with mineral deposits 525

(Masson’s trichome x100). 526

527


of 21

528

Figure 4: Recurrent pyogenic cholangitis. A 16 female presented with recurrent 529

episodes of abdominal pain, fever and jaundice for last many years. Panel (a): ERCP 530

cholangiogram shows marked dilation, elongation and arrow head appearance of left 531

hepatic ductal system with numerous filling defects. Panel (b): Photograph of left 532

hepatectomy specimen showing extensive dilation and destruction of left hepatic 533

ductal system with numerous brown pigment stones. Panel (c): Photograph of soft 534

brown pigment stone. Panel (d): Histological section of a brown pigment stone 535

recovered showing multiple worm segments containing large number of ova of 536

Ascaris lumbricoides encrusted with mineral deposits (Masson’s trichome x100). 537

Manuscript Accepted | Early View Article Journal Name ...How to cite the article: Khuroo MS, Khuroo...

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