Clinical Problems in Gastroenterology Her Hsin Tsai
Page numbers followed by f refer to figure, and t refer to table
acute 55, 58, 71
non-gaseous 10
obstructed 67
Abdominis muscle 336
Abscess 347
amebic 349
anorectal 201
appendix 73
crypt 110f
formation 87
ischiorectal 202f
mesocolic 87
perianal 194
pyogenic 348
Acalculous cholecystitis 76
Acarbose 285
Achalasia 295, 298f, 307
early 307f
late 307f
Acid glycoprotein, serum 147
Acquired immunodeficiency syndrome 160
Adalimumab 150
Addison's disease 118, 260, 268
Adenocarcinoma 6f
esophageal 295
intraepithelial mucous 194
mucinous 198
Adenoma 48
adrenal 247
duodenal 5f
high-risk 253
tubulovillous 250f
Adenomyomatosis 8, 52
Adenylcyclase, colonic 118
Adequate lateral pressure 231f
Adhesions 90
Adrenocorticotropic hormone, intravenous injection of 261
Aerophagia 274
Afferent loop obstruction syndrome 281, 283
Alanine aminotransferase 375, 376, 382
Albumin 358, 383
Alcohol 326, 385, 389
assessment of 377
consumption 267, 375
dehydrogenase 386f
excess 397
metabolism 386f
Alpha chain disease 121, 172
abnormal 380
serum 345
Amebiasis, chronic 163
Ameboma 163
Amenorrhea 269
Ammonia generation 404
Ampicillin 105
Ampulla of Vater 234
Amylase 80
serum 64
intestinal 172
primary 172
Anal fissures, acute 197
Anal mucosa, normal 194
Anchovy sauce 337
Anemia 115, 172, 205, 212, 286, 366
hemolytic 320
pernicious 375
Angiodysplasia 192, 208, 211f, 235
Angiodysplastic lesions 235
Angiogram 371f
Angiography 211, 221f, 222f
Angioplasty, coronary 219
Anorectal problems 191
Anorexia 256, 267, 313
nervosa 269
Antacids 189, 301
therapy 291
Antibiotics 76, 150
broad-spectrum 74
Antibody, antinuclear 379
Anticholinergics 189
Antidiarrheal drugs 134, 166
Anti-helicobacter therapy 31
Antineutrophil antibodies, serum 239
Antireflux surgery 302
Antral gastritis 37
Aortic aneurysm 69
abdominal 69, 341, 342f
large abdominal 224f
ruptured abdominal 94
Aortoenteric fistulae 223
Aphthoid 106
ulcers 113
Appendicectomy 73
Appendicitis 59
acute 70, 73
diagnosis of 75
management of 75
complex neurohormonal control of 266f
physiology of 265
stimulates 266
Argon plasma coagulation 235, 236f
Arrhythmias, cardiac 403
Arteries, inferior mesenteric 52
Arthritis 112
rheumatoid 238
Ascariasis 164
Ascaris lumbricoides 166
Ascites 208, 335f, 356, 359, 371
development of 360
grading of 361t
malignant 336
pancreatic 174
Ascitic fluid 174, 336, 360f
Aspartate aminotransferase 375, 376
Aspergillus flavus 343
Aspirin 214
Autoimmune disease 327, 328
Autoimmune pancreatitis, computed tomography of 174f
Azathioprine 78, 134, 153, 307
Bacillus cereus 162
Back pain 94
Bacteria flora, colonic 127
Bacterial disease 327
Bacterial fermentation 274
Bacterial overgrowth 125
Bacterial peritonitis, spontaneous 361
Balloon tamponade 229
Balsalazide 134
Bariatric surgery 90, 279, 281, 282
four main types of 280f
enema 111, 192
meal 312f
Barrett's esophagus 289, 303, 304f, 313, 314f
Barrett's mucosa 295
Barrett's visible dysplasia 304f
Basal cell carcinomas 194
B-cell lymphoma 47
Behçet's disease 112, 238
Behçet's syndrome 238
Belching 32, 274, 277
Bicarbonate concentration 124
Bile acid
deconjugation of 125
diarrhea 180
Bile duct dilation, intrahepatic 61
Bile salt
diarrhea 118, 284
handling, abnormal 25
malabsorption 104
Biliary atresia 332
Biliary colic, attacks of 75
Biliary duct stones 9f
Biliary gastritis 6f
Biliary reflux following previous gastric surgery 258
gastritis 41
Biliary tract disease 77
Biliary tree 327
congenital malformations of 332
dilation 174f
Biliopancreatic diversion 272, 280, 280f
Biliopancreatic loop 283
Bilirubin 358, 383
conjugated 326
metabolism 320f
inherited disorders of 321, 326
Biological therapy 122, 150
Biopsy 197
esophageal 299f
multiple 43
rectal 104, 109
Bismuth subsalicylate 166
Blatchford score 205, 207, 207t
Bleeding 191, 209, 234, 239
acute 366
colonic 235
hemorrhoids 196f
life-threatening 227
peptic ulcer 213
rectal 115, 199
Blind loop 125
Bloating 23f, 26, 32, 276, 277
electrolytes 269
peripheral 169
pressure 206
labile 79
systolic 207
spotting 191
testing, occult 106
transfusion, history of 378
urea 207
vessels 108f
Body mass index 376, 377f, 378
Boerhaave's syndrome 81, 219
densitometry 170
disease, metabolic 147
growth, normal 380
cancer 240
disease 129
ischemic loop of 58
ischemic 71
large 92
obstruction, large 66f, 94f
wall, infarction of 68f
Bowen's disease 194
Brachytherapy, single-dose 317
Bradycardia 269
Bradykinin 179
Brain tumors 247
Breath, shortness of 55
Bristol stool chart 182, 183f
Bronze diabetes 173
Budd-Chiari syndrome 328
Budesonide 159
Bulimia 270
Calcified vascular atheroma 18
Calcium 380
channel blockers 189
serum 19
Campylobacter 103, 161
enteritis 108
infection 160
jejuni 102, 162
Cancer 132, 141
classic apple-core appearance of 298f
colonic 114f
colorectal 1, 3, 91, 131, 132, 142t, 240, 242f
esophageal 311, 313f, 314f
higher risk of 243
ovarian 3
pancreatic 330, 331, 331f
renal 20f
cell 20f
second synchronous 252
sigmoid 250f
stomach 44f
Candida septicemia 305
Capsule endoscopy 209, 211
Caput medusae 336
Carbohydrate 402, 404
absorption 285
fermentation of 275
handling 276
meal 285
Carbon dioxide 275
Carboplatin, administration of 317
Carcinoembryonic antigen 252
Carcinoid 254
syndrome 117, 179, 342
tumors 254
Carcinoma 43f, 90, 106
cecal 90
colonic 86, 113
epidermoid 198
gallbladder 330
hepatocellular 343, 345, 345f, 367, 367f
invasive 250f
large bowel 89, 91
medullary 180
pancreas 330
renal cell 340f
small intestine 233
stomach 41
Cardiac failure, congestive 328
Cardinal signs 59
Caroli's disease 329
Caroli's syndrome 332, 333
Catecholamines 179
Celecoxib 214
Celiac antibodies 24
Celiac disease 3, 104, 120, 120f, 168, 168f, 212
diagnosis of 169
Central nervous system 121
Central venous pressure 79
Cerebrovascular accident 188
Chagas disease 188, 307
Charcot's triad 61, 327
transarterial 368
transcatheter arterial 346
Chemoradiotherapy, therapeutic 316
Chemotherapy 198, 331
adjuvant 45
neoadjuvant 44, 251
Child-Pugh score 357t
Chlorpromazine 264
Cholangiocarcinoma 327, 329
risk of 329
Cholangitis 51, 77, 327, 393
ascending 77
primary biliary 328, 393
suppurative 77
Cholecystectomy 51
laparoscopic 51
Cholecystitis 51, 74
acute 60, 61f, 75, 77
gangrenous 77f
Choledochal cysts 329, 332
Cholera 117, 178
management of 179
Chymotrypsin, 124
Ciprofloxacin 171
Cirrhosis 147, 356
complications of 356
hepatic 226
plus ascites 364
presence of 383
Cirrhotic liver 357
Clostridium difficile 105, 162
colitis 162, 163f
infection 150, 160
toxin 105
Clostridium perfringens 162
Coagulation disorders 239
Coccygodynia 201
Colectomy, types of 140
Colic, esophageal 290
Colitis 148, 157
chronic low-grade 135
collagenous 22, 103, 157
cystica profunda 199
eosinophilic 159f
ischemic 157
lymphocytic 157
microscopic 157
ulcerative 2f, 3, 87, 106, 107f111f, 113f, 127, 128f, 129, 130f, 253
worse 133
cancer 213f, 240, 252
sporadic 248f
staging of 251
eosinophilic infiltration of 16f
Colonic disease 105, 146, 153
Colonic transit study 187f
Colonoscopy 142f, 210, 237f
virtual 111
Colorectal cancer, risk of 141
Columnar cells, mucin-producing 11f
Common bile duct 52, 175f, 323f
injury 323f
stones 323f
tumor obstructing lower end of 12f
Computed tomography 114f, 250f, 262f, 268f, 324
aortic angiogram 69f
colography 111f
scanning 12f, 341f
abdominal 43
acuminata 194
lata 194, 198
Connective tissue disorders 85
Constipation 25, 98, 182, 185, 188, 188t, 189t
causes of 188
predominant irritable bowel syndrome 185
Corpus gastritis 37
Corticosteroids 78, 133, 149
Corticotropin-releasing hormone 265
Cotrimoxazole 171
Courvoisier's law 61
Coxiella burnetii 327
Cramps, abdominal 285
C-reactive protein 2, 59, 104
Creatinine 384
Cricopharyngeal spasm 309
Crigler-Najjar syndrome 321
Crohn's disease 1, 2, 2f, 14, 14f, 20, 25, 74, 87, 90, 104, 110f, 111f, 112, 113f, 118, 122, 127, 128f, 142144, 145f, 148, 151f, 153, 157, 177, 192, 194, 197, 202, 203f, 204, 233, 235, 238, 342, 404
classic hallmarks of 146f
colonic 150
diagnosis of 15f
management of 149
natural history of 148f
perianal 156
prevalence of 143
specific complications of 154
Cronkhite-Canada syndrome 255
Cruveilhier-Baumgarten syndrome 227
Cryptosporidium 103, 161
Cullen's sign 57, 62
Curling's ulcers 35, 219
Cyanosis 299
Cystic fundic polyps 48
Cysts 163, 164
hepatic 347
Cytochromes 98
Cytomegalovirus 305, 327, 353, 379
biopsies 292f
inclusion body 306f
serology 379
Degos disease 239
Deoxyribonucleic acid 386
Dermatitis herpetiformis 169
Dermatomyositis 238
Desmoid tumors 247
Diabetes 173, 378, 388
mellitus 188
Diarrhea 3, 17, 25, 26, 102, 104, 105, 109, 112, 112f, 117, 127, 173, 179, 276, 281, 284
bloody 157
chronic 106
infective 103, 108, 160
inflammatory infective 103
large volume 117
nocturnal 104
non-bloody 259
non-inflammatory infective 103
predominance of 24
secretory 178, 179
watery 117, 118, 159, 180
Diclofenac 214
Dietary therapy 152
Dieulafoy's lesion 220, 221f, 222f
Digoxin 105
Directly acting oral anticoagulants 208
Distension, abdominal 65, 276, 335f
Diuretics 78
Diverticular disease 18, 63
Diverticulitis 18, 63, 85, 87, 88
Diverticulosis 235
Diverticulum, esophageal 310, 310f
Domperidone 302
Dopaminergic antagonists 264
Drug 258, 326
efficacy 135
history 378
therapy 149, 229, 306, 308
Dubin-Johnson syndrome 326, 384
Dumping syndrome 284
frequency of 281
biopsies, endoscopic 171
disease 3
Jejunal flexure 95
obstruction 258, 331f
perforation 83
acutely bleeding 215
management of 29
multiple 5
perforated 84
posterior 3
Duodenitis 7, 31
Duodenum 10
Dupuytren's contracture 386
Dysentery, amebic 163
functional 32, 33
non-ulcer 32
Dysphagia 283, 292, 293, 308, 309, 312, 313, 400, 403
esophageal 293
oropharyngeal 293
Dysplasia 132, 141
high-grade 141, 304f
Dyspnea 299
Eating disorders 265
Echinococcus granulosus 347
Ectopic pregnancy 70
rupture of 69, 70
Ehlers-Danlos syndrome 239
Electrolytes 80
Emergency laparotomy 71
Empyema 71, 75, 338
Encephalopathy 356, 359, 364, 371
grades of 365t
hepatic 229
Endocrine disease 118
Endocrinological disorders 188
Endometriosis 20
Endometriotic cyst, spontaneous rupture of 70
Endomysial antibodies 120
Endoscopic therapy 216, 217, 229
Entamoeba coli 103
Entamoeba histolytica 161, 163, 349
Enteritis, eosinophilic 16f
Enterobiasis 165
Enterobius vermicularis 165, 165f, 195, 201, 201f
Enteroenteric anastomosis 281
Enteroscopy 211
Enzyme 376
concentration 124
hepatic 259
Eosinophil infiltrates 299f
Eosinophilic enterocolitis, diagnosis of 16f
Epilepsy 98
Episiotomy 193
Epithelioid cells 117f
Epithelium 120
serology 379
virus 327, 379, 393
Erythema nodosum 147, 162
Erythrocyte sedimentation rate 2, 104
Erythromycin 105, 167
Escherichia coli 103, 327, 349
advanced 317
large 315f
treatment of 318
candidiasis, extensive 305
disease, antigen-mediated 306
eosinophilia, causes of 306
mucosa, transformed 295
perforation, prognosis of 82
sphincter, lower 288, 289, 301, 307f, 308
stricture, balloon dilation of 305f
ulcer, benign 296f
Esophagectomy 316
Esophagitis 300
eosinophilic 298, 299f, 305
infective 305
Esophagogastric junction cancers 317
Esophagus 288
ulcerated peptic stricture of 296f
Ethanol 386
Extrahepatic ducts 332
intolerance 32
malabsorption 173
Fatigue 284
Fatty acids, short-chain 274, 404
Fatty diarrhea 118
Fatty liver 385, 387f
disease 406
non-alcoholic 361, 376, 378, 380, 388
Fecal blood loss 252
Fecal calprotectin 2f, 104
level of 24
Fecal incontinence 193, 200
Fecal peritonitis 88
Fecal transplant 162
Fever 327
Fibromuscular ring 297
Fibrosis 174f, 356f, 387f
tissue 195
Fissure, anal 188, 197
Fistula 154, 194
anorectal 202
formation 87
Fitz-Hugh-Curtis’ syndrome 70
Flexible sigmoidoscopy 105
Flucloxacillin 326
Fludeoxyglucose 314
Fluid and electrolyte replacement 179
Food poisoning 161, 257
causes of 162t
Forceps delivery 193
Fragile superficial capillaries 238f
Fundic gland polyps 49f
Fungal infection 198
Gallbladder 8, 52, 71, 324, 331f, 338
adenomyomatosis of 8
cancer 330
disease 7
distension 339
fossa 65f
palpable 61
ultrasound scan of 61f
wall 61
Gallstone 7, 9, 50, 52, 56, 61, 75, 76, 147, 281, 282, 282f, 324
development 283
disease 282
management of 325f
formation of 51, 282
medical management of 52
related disease 78, 80
Gamma glutamyl transferase 376, 380, 381
Ganglioneuroblastoma 178
Gas production, causes of 23
Gastointestinal bleeding 213
partial 286
vertical sleeve 272
acid 286
adenocarcinoma 43f
antral vascular ectasia 36, 36f
band 272
laparoscopic adjustable 280f
placement 279
bypass 280
cancer 38, 41, 44f, 45, 267
early 45
large 42f
management of 43
treatment of 45
carcinoma 258
dilatation, risk of 270
disease 3
distension, acute 281
emptying study 260
erosions 219
inhibitory polypeptide 285
lymphoma 45, 46f48f, 223, 223f
malignancies 45
metaplasia 31, 32
mucosa, eosinophilic infiltration of 39
mucosal inflammation 36
neoplasm 83
operations 279
numbers of 279
outlet obstruction 261
parietal cells 30f
pathology 261
perforation 83
polyps 48
scanning 260
benign 35
margin, histology of 28f
perforated 83
risk of 36
varices 231, 232f
volvulus 18f, 311, 312f
Gastrin 30f, 33
acetylcholine 30f
producing tumor 5
secreting pancreatic tumor 117
Gastrinoma 6
duodenal 6
Gastritis 36, 36f, 37t, 38, 39, 262
acute 37
alcoholic 257, 258
atrophic 40
chronic 37
eosinophilic 40
granulomatous 39, 40
helicobacter-associated 40
hypertrophic 39
infectious 39
lymphocytic 40
severe 38f
viral 257
eosinophilic 158
viral 168
Gastroenterology 258
junction 279, 288, 316
reflux disease 300, 306
tumor 298f
varices 227
abdominal pain, upper 4
bleeding 205, 359, 366
severe 205
upper 192
disorders, upper 288
disturbance 55
endoscopy, upper 209
infection 256
motility 265
stromal tumor 50, 50f, 222, 222f
tissue 158
tract 264, 365
function of 399
primary function of 183
spontaneous perforation of 80
Gastroparesis, diabetic 258, 260f
Gastropathy, portal hypertensive 233
Gastropexy, vertical band 280
Gastroplasty, vertical banded 280f
Genetic syndromes 242
Ghrelin 265
Giant cell granulomas 117f
Giardia 102, 103
lamblia 121, 161, 166
infestation 163
Giardiasis 163, 170
Gilbert's syndrome 321, 384
Globus hystericus 292
Glomerulus 62
Glottis 81
isotope of 45
tolerance tests 173
Glyceryl trinitrate 197, 229
Glycocholate breath test 126
Glycoprotein 252
Granulomas 111f
Granulomata, non-caseating 106, 146, 146f
Granulomatous disease 381
Grey Turner's sign 57
Gynecomastia 335f, 357f
Hartmann's pouch 339
Hartmann's procedure 93
injury 188
tumor, pancreatic 12f
Headaches 284
Heart disease, ischemic 36, 229
Heartburn 33, 288
Helicobacter pylori 4, 26, 28, 30, 37, 38, 38f, 219, 281
diseases, putative pathogenesis of 29f
eradication 29
infection 27, 31, 37, 47, 48f, 213, 214
Heller's procedure 308
Hemangiomas 346
Hematemesis 209
Hematochezia 205
Hematoma 69f
perianal 195
Hemochromatosis 173, 343
hereditary 380, 396
Hemoglobin 207
Hemolysis 320
Hemorrhage 208
acute 213f
recent 206, 206t
spontaneous 108f
Hemorrhoids 195, 196f
thrombosed 188
Henoch-Schonlein purpura 239
cyst, simple 337, 348f
fibrosis, congenital 332, 333
mass, irregular 344
venous flow, assessment of 339
A 353
virus 392
acute 258
alcoholic 368, 386
alcoholic 358, 369f
autoimmune 321, 328, 376, 379, 394
B 343, 353, 354, 379
core antibody 390
surface antigen 390
virus 344, 376, 379, 389, 390t, 391
C 353, 379
virus 344, 379, 391, 392
chronic 147
D virus 391
infection 391
E virus 392
evidence of 259
viral 357, 378, 389, 392, 397
Hepatocellular carcinoma
development of 358
primary 343, 344f
Hepatoma 343, 344
Hepatorenal syndrome 359, 361, 363
development of 363f
diagnosis of 364t
types of 364t
Hereditary colorectal cancer syndrome 246
Hernia 90
hiatus 17f, 219, 288, 311
internal 281, 282
para-esophageal 311
umbilical 91f
Herpes simplex virus 305
High jugular venous pressure 336
Hinchey classification 63
Hirschsprung's disease 188, 189, 336
Histamine 179
H2 antagonists 301
receptor 30f, 264
Hormonal signals, peripheral 265
adrenocorticotropic 313
metabolic 273
production of 265
Howell-Jolly bodies 120
Human immunodeficiency virus infection 305
Human papillomavirus, types of 197
Hydatid cysts 347
Hydrogen production 274
Hyperbilirubinemia 319, 384
conjugated 320, 321
unconjugated 320
Hypercalcemia 19, 188, 258, 261
Hypercholesterolemia 378, 388
Hyperemesis gravidarum 258, 384
Hyperglycemia 266
Hyperlipidemia syndromes 19
Hyperparathyroidism 188
crypt 120
lymphoid 73
Hypertension 98, 378, 386, 388
management of 388
portal 225f, 226
Hyperthyroidism 261
Hypoalbuminemia 361
Hypochlorhydria 117
Hypokalemia 188
Hypolactasia 164, 167, 170
Hyponatremia 361
Hypophosphatemia 403
Hypotension, postural 260
Hypothalamus 266
Hypothyroidism 188
Hypovolemia 359
signs of 359
Hypoxemia, severe 78
Ibuprofen 214
Ileal disease, terminal 153
Ileitis 148
Ileocecal valve 107f
Ileocolitis 148
Iliac fossa 336, 341
Immune disease, history of 394
Indomethacin 214
Infarction 68
intestinal 67
Infectious disease 324
Infective diarrhea
causes of 160
consequences of 160
Infertility 70
Infiltrative lymphoma cells, proliferation of 47f
chronic 106
severe 163f
sigmoid 16f
Inflammatory bowel disease 1, 56, 87, 103, 136f, 192, 213, 235, 244
Infliximab 150
Interleukin 160
bacterial overgrowth, small 125, 177
cancers, range of 270
disease 12, 120, 126
infarction 17
ischemia 96
obstruction 65, 88, 89, 96, 262
diagnosis of 65, 92
peptide, vasoactive 178, 179
contractions of 12
small 164, 178
vasculitis of 238
Intra-abdominal pathology 64, 96
epithelial neoplasms, malignant 11f
papillary mucinous neoplasm 330
Intrahepatic ducts, dilated 12f, 13f
Intrathoracic pressure 256
deficiency 286
replacement therapy, simple 286
Irritable bowel syndrome 1, 2f, 3, 21, 24, 104, 184, 192, 276, 335, 335f
postinfective 23
Ischemia 67
intestinal 53
mesenteric 17, 52
Jaundice 208, 319, 319f, 326, 327, 332, 359, 378
degree of 7
radiological investigation of 324t
Jugular venous pressure 362
Kasai portoenterostomy procedure 332
Kelly-Patterson syndrome 310
Kernicterus 321
Ketoprofen 214
Kidney 340
injury 359
Labyrinthitis 258
Lactulose syrup 126
Lamina propria
colonic 146f
edematous 254
mononuclear cells 169
Lansoprazole 105
Lanugo hair 269
Lanz incision 75f
Laparotomy, second-look 86
Large bowel obstruction, management of 93
Leptospira icterohemorrhagica 327
Leukemia 197
Leukocytes 133
Leukoplakia 198
Leukotriene receptor antagonist 159
Lichen planus 198
Linitis plastica 41, 42f, 401
infiltrative gastric cancer of 262f
Lipoma, esophageal 297f
abscesses 338f
causes of 349
biochemistry, abnormal 375, 382
biopsy 345, 382
cirrhotic 356f
disease 227, 228, 358, 375, 384
alcohol-related 385, 386, 387f
autoimmune 379, 393
chronic 324, 335f, 351, 356, 357, 357f, 377
history of 352
inherited 396
severity of 358
signs of 208
stage of 358
enzyme 375
failure 351, 361
acute 351, 351f, 352f, 355
acute-on-chronic 369
chronic 353
encompasses 351
function test 324, 376, 377f, 382
abnormal 7, 147, 375
metastases 44f, 316f
resection 345
screen, noninvasive 376, 378
synthetic function 362
transplantation 333, 355, 373
tumors 343
Local disease, management of 316
Lymph nodes
abdominal 341
enlarged 223f
Lymphangiectasia, intestinal 121
Lymphocytes 120
intraepithelial 168
Lymphoid tissue, mucosa-associated 47, 48f
Lymphoma 90, 253
intestinal 121, 169, 171, 172
mediterranean 172
primary 172
Lynch's syndromes 247, 248
Macroamylasemia 62
Maddrey's discriminant function 369
Magnetic resonance
cholangiopancreatography 323f, 324
enteroclysis 121, 155f
enterography 3
imaging 13f, 14f, 113f, 203f
causes of 121
severe 172
Malignant disease
exclusion of 267
occult 19
Mallory's hyaline 387f
Mallory-Weiss tear 209, 219, 220f
Mallory-Weiss type 220
Malnutrition, risk of 399
abdominal 334
appendix 73
central abdominal 341
lower abdominal 58
pancreatic 341
renal 340
suprapubic 341
Mast cell stabilizer 159
McBurney's point 59
Mebendazole 348
Meckel's diverticulitis 74
Meckel's diverticulum 209, 210
Melanomas 194, 198
Melanosis coli 115f
Meloxicam 214
Memory T-lymphocytes, migration of 135
Ménétrier's disease 39
Menetrier's hypertrophic gastritis 262
Meniere's disease 258
Menopause 393
Mesalazine 150
Mesenteric artery syndrome 52, 263
Metabolic disease 19
exclusion of 268
Metabolic disorders 188
Metabolic syndrome 375, 388
Metaplasia 132, 303
intestinal 38
Metastatic disease, management of 317
Metformin 105
Metoclopramide 209
Metronidazole 150
Micronutrient 405
deficiencies 286
Mirizzi's syndrome 7, 339
Mononucleosis, infectious 393
Monospot test 393
Motor neuron disease 293, 310
Motor neuropathy 98
Mucocele 75, 338
colonic 137f
rectal 103, 106
Murphy's sign 60
antibody, smooth 394
hyperplasia, smooth 254
involvement 172
Muscular tear 82
Myasthenia gravis 293
avium-intracellulare 39
bovis 167
tuberculosis 167
Myocardial infarction, acute 81
Myotomy, per-oral endoscopic 308
N-acetyl cysteine 354
Naproxen 214
Nasogastric tubes 405
National Institute of Clinical Excellence 21, 152
Nausea 32, 65, 256, 257, 259
causes of 257, 258
neurophysiology of 256
painless 257
N-benzoyl-l-tyrosyl-p-amino-benzoic acid 124
develops, pancreatic 78
pancreatic 79
Neoplasms, pancreatic 341
Neoplastic disease 20
Nephrotoxic drugs 364
Nervous system, sympathetic 363
Neural tissues 178
Neurokinin 256
Neurological disease 293
Neurological disorders 188
Neuromuscular disease, primary 293
Neuropathy, diabetic autonomic 188
Neutrophil 103
infiltration 369f
Neutrophilia 67
Nitrogen 274
source 403
Nodules, regenerative 356f
Nonsteroidal anti-inflammatory
agents 56, 213
drugs 4, 189
Non-variceal upper gastrointestinal bleeding, causes of 219
Nosocomial infection 162
Nutritional status, assessment of 399
Oat cell carcinoma 178
Obesity 270, 279, 357, 375, 397
endoscopic appearance of 284f
gastrointestinal complications of 279
Obstruction, relief of 329
Octaplas 228
Octreotide 51, 286
scan 34f
Odynophagia 288, 291, 305
Ogilvie's syndrome 66, 92
Olsalazine 134
Opiate analgesia 76
Opioids 189
Oral mesalazine 136
Oral metronidazole 162
Oral ulcer 112, 145f
Osteomalacia 147
Osteopenia 147
Osteoporosis 147
Ovarian cyst, torsion of 70
Oxygen therapy 79
Paddy fields 164
Paget's disease 194, 195, 198, 380
Pain 192, 327
abdominal 2, 14, 19, 20, 22, 55, 58, 65, 73, 98, 172, 173, 257, 281
agonizing 67
anal 192
biliary colic 7
cardiac 290
chest 55, 81
chronic abdominal 1, 21
epigastric 32, 72
esophageal 288
functional 1
management of 331
organic 1
periodic 27
rectal 201
recurrent abdominal 21
upper abdominal 72
Palmar erythema 335f, 357f, 378
Pancolitis 133
Pancreas 6, 178
atrophic 175f
computed tomography of 123f
intraductal papillary mucinous neoplasm of 11f
magnetic resonance imaging of 124f
Pancreatic cancer, magnetic resonance imaging scan of 331f
Pancreatic disease 10, 122, 124
benign 124
malignant 124
Pancreatic duct 175f, 234
dilated 13f, 175f
Pancreatic function tests 123
Pancreatic imaging 123
Pancreatic insufficiency 104
Pancreatic lesion 10
endoscopic ultrasound of 332f
Pancreatic malignancy 329
Pancreatitis 51
acute 56, 61, 62, 62f, 77, 80
alcohol-related 78
autoimmune 173
azathioprine-induced 11f
chronic 13f, 123f, 124f, 174f, 177
severe 78
Pangastritis 37
Para-aminobenzoic acid 124
Paracentesis, large volume 362
Parasites 163
Parasitic disease 327
Parathyroid 6
Parenteral nutrition 405
Parietal cell 30
function 30f
Parkinson's disease 188
Parotid gland 386
Peg solution 263
abscess 87, 192
computed tomography scan 43
esophageal stricture 304
floor dysfunction 187
pain 20, 70, 192
peritonitis, acute 71
ulcer 35, 74
disease 37, 208, 214
Peptide secreting tumors 178
management of 179
Percutaneous transhepatic cholangiogram 12f, 329
Perianal disease 148, 156, 156f, 203f
Pericholangitis 147
cavity 85
irritation, signs of 76
Peritonitis 65
feculent 87
lower abdominal 85
purulent 87
Petersen's hernia 90
Peutz-Jeghers polyps 254
Peutz-Jeghers syndrome 233
Pharyngeal pouch 294f, 309
Phosphatase, alkaline 376, 380, 382
Phosphate 380, 403
Phrenic dyssynergia 23, 276f
Pigment lesions 234
Pinworm 165
Piperacillin 229
Piroxicam 214
cortisol 261
potassium 261
viscosity 2
Plexus hematoma, external 197
Plummer-Vinson syndrome 310
Pneumatic balloon, large 309f
Pneumatosis 117f, 237f
coli 237
computed tomography of 237f
management of 237
cystoides intestinalis 116f
intestinalis 68f
Pneumomediastinum 82f
Pneumoperitoneum 64f, 65f
Polya gastrectomy 125
Polyarteritis 96
nodosa 238
Polycystic liver disease 332
Polycythemia rubra vera 328
Polyethylene glycol 15, 186
Polymyositis 293
Polyp 244
adenomatous 242
benign 90
classic adenomatous 243f
colonic 254
colorectal 240
dysplastic 245f
hamartomatous 254
hyperplastic 244, 254
juvenile 254
metaplastic 254
numbers of 244
Polypeptide, pancreatic 265
esophageal tumor 297f
lesions, management of 52
coli, adenomatous 246
familial adenomatous 48, 246
syndromes 48, 49f
Porphyria 19, 98
intermittent 56, 98
Portal hypertension 208, 356
clinical features of 227
development of 357
etiology of 225
pathogenesis of 225
presinusoidal 225
sinusoidal 226
Portal pressure, normal 225
Portal vein thrombosis 225
diagnosis of 226
Portal venous gas 67
Positron-emission tomography scan 45
Potassium 403
serum 285
Prader-Willi syndrome 265
Preeclampsia 385
Pregnancy, intrahepatic cholestasis of 384
Prochlorperazine 264
Procidentia 199
Proctalgia 201
fugax 192
Proctitis 139
ulcerative 192
Prolactinoma 6
Prophylactic antiemetics 259
Prostaglandin inhibitors 133
Protein energy malnutrition 370
Prothrombin 259
time 352
Proton 30
pump 30
inhibitors 30, 282, 289, 302
Pruritus 195
ani 195, 200
Pseudoachalasia 308
barium swallow of 298f
phenomenon of 297
Pseudocyst 174
large pancreatic 342f
Pseudomembranous colitis 87, 105, 160
Pseudo-obstruction 92
Psychology 22
Psychosis 98
Puborectalis straightens 184f
Pus cells 103
Pyloric stenosis 258
Pyoderma gangrenosum 131f
Pyrexia 61
presence of 337
Radiation proctitis 116f, 238, 238f
Rapid dehydration, causes of 56
Reactive oxygen species 386
Rectal mucosa, normal 106
Red blood cells 320
Refeeding syndrome, risk of 401
disease, endoscopy of 290f
esophagitis 300
gastritis, alkaline 39
Reiter's syndrome 162
Renal artery, lower border of 96
Renal disease 356
intrinsic 364
Renal dysfunction 384
Renal impairment 359, 374
Retinal pigment epithelium, congenital hypertrophy of 246
Retrograde cholangiopancreatography, endoscopic 324, 325f, 395f
Reye's syndrome 259
Rheumatoid disease 173
Ribavirin 392
Rockall score 206f, 206t
Rokitansky-Aschoff sinuses 8
Roundworm 164
gastric bypass 272, 280, 280f
reconstructions 286
type operations 281
Saliva, outpouring of 35
Salmonella 103, 161, 162
infection 160
osteomyelitis 161
septicemia 161
typhi 349
Salpingitis, acute 70
Sarcoidosis 40
Schatzki ring 297, 311
Schistosome 164
Schistosomiasis 164
haematobium 164
japonicum 164, 166
mansoni 164
Sclerosing cholangitis, primary 129, 132f, 245, 395, 395f
Sclerosis, multiple 188
Sclerosus et atrophicus 198
Selective serotonin reuptake inhibitors 26
Sepsis, signs of 359
Serious organic diseases 21
Sertoli cell tumors 255
Sexual abuse 192
Sexually transmitted disease 194, 197
Shigella 103, 161
dysentery 167
Shock, absence of 364
Sickle cell anemia 320
Sigmoidoscopy, rigid 105
Sjögrens’ syndrome 173, 289
Skin disease, chronic ulcerating 130
Small bowel 90, 121
bacterial overgrowth 284
infarction 68f
obstruction 58, 66f, 89f, 154f
causes of 89, 90
management of 92
perforation 84, 85t
Snail track ulcers 106
cromoglycate 159
hydroxide, pellet of 105
retention 361
Solitary rectal ulcer syndrome 189, 190f, 198, 199f
Spasm, esophageal 292f, 308
Spider naevi 208, 357f, 378
Spinal cord lesion 188
Spleen, palpable 339
Splenic atrophy 169
Splenic flexure 158
Sporadic colon cancer, pathogenesis of 247
Squamous carcinoma in situ 194
Squamous cell
cancer 312
esophageal cancer 317
Staphylococcus aureus 162
Steatorrhea 103, 120, 118, 122, 125, 173
necessitates 122
Steatosis 147, 369f
Stenosis, stomal 283
Stercoral perforation 86
Steroid 153
budesonide 150
Stomach, fundus of 221f
Streptococcus faecalis 349
Streptococcus milleri 349
Stroke 188
Strongyloides 121
stercoralis 166
Strongyloidiasis 164, 170
Sulfasalazine 133, 150
Swallowing 288
abdominal 334
generalized 334
parotid 208
Sydney classification 36
Syphilis 197, 198
Systemic lupus erythematosus 238
Tachycardia 98
Tapeworm 347
Tazobactam 229
T-cell lymphoma 169
hemorrhagic 234
hereditary hemorrhagic 234
Telangiectatic lesions 115
Tenesmus 193
Thalassemia 320
Theophylline 105
Thiazide diuretics 105
Thiersch procedure 199
Thiopurine S-methyltransferase 134
Thoracic cavity 82
Thumbprinting, classical sign of 96
Thyroid 178
capillary carcinoma of 247
Thyrotoxicosis 118, 258
Tissue transglutaminase 120
Toxic albendazole 348
Toxic alkaloids 227
Toxic gluten 169
Toxic megacolon 138
Transjugular intrahepatic portosystemic shunt 362, 370, 371, 371f
complications of 372f
contraindications of 372f
Traveler's diarrhea 161
causes of 161t
Trichophagia 262
Trichotillomania 262
Trichuris 165
trichiuria 166
Triosorbon 152
Tropheryma whippelii 171
Tropical sprue 170
Trypanosoma cruzi 308
Tubeless function tests 124
Tuberculosis 197
gastrointestinal 122, 167
intestinal 167
anal 198
benign 295
duodenal 233f
esophageal 316f
hepatic 346
metastatic 347
necrosis factor 122, 135
neuroendocrine 34f
obstructing 188
ovarian 255
pancreatic 10, 13f
renal 341f
testicular 255
Turcot syndrome 247
Turner's sign 62
Two-stage ileoanal pouch operation 141f
Ulcer 56
colonic 235
excavated 210f
fissuring 15f, 110f
disease 32f
duodenal 4, 38, 213
duodenal 5f, 26, 215f
endoscopic appearance of 215t
genital 112, 238
pre-pyloric 4f
serpiginous 145f
solitary 235
stomal 281
Ultrasound 324
endoscopic 44, 175f, 224f, 308
scanning 376
Umbilicus 336
Uremia 258
Urinary retention, acute 58
Uveitis 112
Vagus nerve releasing acetylcholine 30f
Variceal bleeding 229, 366, 371, 372
management of 227, 366
Varicella zoster 353
Varices 231
portosystemic 227
Vascular bowel disease 56
Vascular occlusion, mesenteric 96
Vedolizumab 135, 150
hepatic 371f
periumbilical 336
Veno-occlusive disease 227
Venous thrombosis 68, 112
Verner-Morrison's syndrome 117
Vibrio cholerae 162, 178
Vibrio parahaemolyticus 162
Villous adenoma 250f
Villous atrophy 120, 168
Vipoma 117
Viral disease 327
Viral hepatitis infection, chronic 375
deficiency 125
malabsorption 125
D 380
K 383
Volvulus 15
organoaxial 312f
sigmoid 17f
Vomiting 65, 98, 256, 257, 259, 283
causes of 257, 258
drug therapy of 264
epidemics of 259
neurophysiology of 256
psychogenic 263
self-induced 270
severe 258
von Willebrand's disease 240
anal 197
genital 198
Watermelon stomach 36f
Weil's disease 327
Whipple's disease 121, 171
Whipple's procedure 331
Whipworm 165
White blood count 59
Wilkie's syndrome 263, 263f
Wilson's disease 259, 321, 396
enteritis 162
enterocolitica 167
infection 74
Zieve's syndrome 324, 326
Zollinger-Ellison syndrome 31, 33, 34f, 49, 117
diagnosis of 5, 34
management of 34
Chapter Notes

Save Clear

Chronic or Recurrent Abdominal PainCHAPTER 1

Her Hsin Tsai
Is the Pain Functional or Organic?
The vast majority of patients who consult a doctor, especially in the primary care sector, with chronic abdominal pain, will have a functional rather than organic cause for the pain. Over-investigation of such patients is often counterproductive. Many of these investigations are unpleasant, even painful and associated with considerable cost and patients often get alarmed by the number of investigations and they tend to equate that to serious illness. It is therefore essential that the physician identifies those patients positively rather than negatively by excluding a whole lot of organic diseases.
Based on the UK general practitioner studies, the UK general practitioner with an average patient list will encounter over 25 new cases of functional bowel problems compared to a probability of 1 incidental case of colorectal cancer and the average general practitioner will encounter inflammatory bowel disease like a new case of Crohn's disease once every 7 years or more. Identifying the individuals who are likely to have an organic disease rather than a functional disease is therefore very important. Probably the single most important consideration is the patient's age. It is unsafe to label any chronic abdominal pain developing for the first time in a patient over 40 years of age as functional without further investigation. If the patient is under 40 years of age, then it is important to try to make a positive diagnosis of functional pain, such as irritable bowel syndrome (IBS), from the history and ask specific questions if the answers are not provided spontaneously. These questions include:
  • Is the pain associated with gaseous distention?
  • Is the pain associated with constipation or diarrhea?
  • Is the pain relieved by defecation?
  • Is the pain an intermittent pain and interspersed with episodes of trouble-free days or weeks?2
A positive answer to the above questions usually suggests functional abdominal pain. Conversely, the pain is usually more likely to be organic and warrants further investigation regardless of the age if:
  • It awakes the patient at night.
  • It persists for weeks or many months.
  • It is associated with persistent rather than intermittent alteration of bowel habit.
  • It is accompanied by weight loss or rectal bleeding.
Thorough general examination including rectal examination and a few blood tests should usually suffice. A blood test should include full blood count, erythrocyte sedimentation rate (ESR) or plasma viscosity and liver function tests (LFTs) as found in many automated serum profiles. Even if these are normal one can miss inflammatory bowel diseases, particularly Crohn's disease, especially if the patient comes from a high-prevalence country. Serum acute phase reactant test like C-reactive protein (CRP) can also be quite useful as it does reflect an inflammatory process. More recently, fecal calprotectin has been shown to be useful in differentiating between inflammatory bowel conditions and those with normal or IBS (Fig. 1.1). The prevalence of the conditions and incidental cases per year, per general practitioner, is given in Table 1.1.
A simple diagnostic algorithm to differentiate between IBS and other causes of abdominal pain is illustrated in Figure 1.2. When a physician encounters a patient with abdominal pain with some bowel symptoms, it is important to try to make a positive diagnosis of IBS early. This will reassure the patient, enable early implementation of treatments and prevent unnecessary and painful investigations.
zoom view
Fig. 1.1: Fecal calprotectin IBS or IBD. **p<0.01, ***p<0.001. (CD: Crohn's disease; UC: Ulcerative colitis; IBS: Irritable bowel syndrome; NC: Normal controls.)
Table 1.1   Likelihood of general practitioner (GP) episode.
Prevalence (%)
Incidence cases/year/GP
Crohn's disease
Ulcerative colitis
Ovarian cancer
Celiac disease
Colorectal cancer
Irritable bowel syndrome
zoom view
Fig. 1.2: Diagnostic algorithm for IBS.
(IBS: Irritable bowel syndrome; IBS-C: IBS-constipation; IBS-M: IBS-mixed; IBS-D: IBS-diarrhea; MRE: Magnetic resonance enteroclysis)
Symptoms that should concern the physician are:
  • Age over 40 years
  • A strong family history of colorectal cancer or inflammatory bowel disease, any rectal bleeding
  • Anemia
  • Weight loss or
  • Palpable abdominal mass.
If they do not have these symptoms, then the physician should proceed to obtain fecal calprotectin and, if that is negative, a firm diagnosis of IBS can be made. For the case of predominant diarrhea, refer to Chapter 3 for reaching a diagnosis.
Is it Due to Gastric or Duodenal Disease?
When pain is due to gastric or duodenal disease, it is usually in the epigastric region. Sometimes with posterior duodenal ulcers, the pain can radiate through to the back, but in general the pain is often poorly localized. A typical history would be of a patient being awakened at night with these symptoms and this is usually in the early hours of the morning. It is often periodic, it may last several weeks separated by weeks or months without pain.4
Patients taking nonsteroidal anti-inflammatory drugs (NSAIDs) may have duodenal ulcer disease with little or no symptoms at all, probably due to the analgesic effects of non-steroidal drugs themselves. As a result, they may present late and perhaps with a complication like bleeding or perforation. A history of drug use is important, therefore as part of the work-up for these patients.
The best way of diagnosing patients with upper gastrointestinal (GI) abdominal pain is to perform an endoscopy (Figs. 1.3 and 1.4). In patients under the age of 40 years, it is not unreasonable to carry out non-invasive investigations before considering an endoscopy. This could be a Helicobacter pylori fecal antigen test which is a simple and low-cost investigation. If the patient is young and presents with predominantly dyspeptic symptoms, it is also not unreasonable to give a trial of a proton pump inhibitor (PPI) like lansoprazole or omeprazole to see if it alleviates the symptoms. However, in areas where there is a high incidence of gastric cancer, it is not unreasonable to perform a prompt endoscopy in order to detect early cases of gastric cancer.
Duodenal ulcer disease is associated with Helicobacter infection in the majority of patients without a history of non-steroidal use. The easiest and cheapest method of detecting H. pylori with a high degree of sensitivity and specificity is the fecal antigen test. However, other tests such as blood serum antigen testing and urea-based breath tests are also available.
Endoscopy remains the investigation of choice when there is a suspicion of gastroduodenal disease. A well performed endoscopy can be done without sedation or under light sedation and is usually very well tolerated. This would also be able to pick up suspicious pathology like early gastric cancer. If the endoscopist encounters an ulcer in the stomach, it would be mandatory to biopsy it and also to review it at an interval of 6–8 weeks after treatment to make sure it is healed completely.
zoom view
Fig. 1.3: Pre-pyloric ulcer: This ulcer sits at the pyloric opening.
zoom view
Fig. 1.4: Duodenal ulcer: The most common location is the first part of the duodenum.
zoom view
Fig. 1.5: Duodenal adenoma: This is a benign lesion with malignant potential and can be removed endoscopically. Usually found around the papilla, this one in the first part of the duodenum is rare. May be associated with colonic polyposis syndromes hence colonoscopy should be offered.
This is to make absolutely sure that we are not dealing with gastric cancer. Ulcers in the first part of the duodenum are almost always benign, but malignant lesions can occur in the duodenum but tend to be in the second or third part of the duodenum or associated with the ampulla of Vater. A well-performed endoscopy should exclude all these possible lesions (Figs. 1.5 to 1.7).
A diagnosis of Zollinger–Ellison syndrome (gastrin-producing tumor) should be considered if there are extensive multiple duodenal ulcers or patients with ulcers resistant to treatment with PPIs, patients with extensive ulcers who are Helicobacter negative or continue to have ulcers after 6Helicobacter eradication. Investigations for Zollinger–Ellison syndrome include a fasting gastrin level. Sometimes calcium levels may also be elevated in MEN1 (Multiple Endocrine Neoplasia Type 1) syndrome. These patients have tumors in the 3 Ps—pituitary (e.g. prolactinoma), pancreas (gastrinoma), and parathyroid. The gastrinomas tend to be multiple. Imaging with computed tomography (CT) scanning is often sufficient to locate the lesions but other modalities like magnetic resonance imaging (MRI) can also be very useful. Transabdominal ultrasound may even be sufficient in some cases of locating a lesion. Pancreatic gastrinomas can also be localized using endoscopic ultrasonography, which has a higher sensitivity and specificity for pancreatic and duodenal gastrinomas.
zoom view
Fig. 1.6: Biliary gastritis. Bile reflux into the stomach can be readily seen at endoscopy and the accompanying mucosal inflammation makes it an easy diagnosis.
zoom view
Fig. 1.7: Retroflexing the scope reveals a raised lesion with altered blood. This is an adenocarcinoma.
Duodenitis is usually an endoscopic or histological diagnosis rather than a clinical one. Many patients with duodenitis have little or no symptoms or symptoms that are indistinguishable from duodenal ulceration. Treatment is purely symptomatic.
Is it a Gallbladder Disease?
Gallstones are extremely common and are frequently completely asymptomatic. A common error is to attribute nebula symptoms of abdominal discomfort, bloating and fat intolerance to the gallstones. This may lead to unnecessary cholecystectomy. Patients would then still complain of the same functional symptoms despite the cholecystectomy. It is therefore important to make the firm diagnosis that the symptoms are attributable to the presence of gallstones.
Gallstones can cause two varieties of pain. This may be due to inflammation or it could be due to stones or tumor that is obstructing the outflow of the gallbladder. Forcible contractions against such an obstruction would result in pain. Pain also occurs if the gallstones are impacted infundibulum or the neck of the gallbladder or if they are extruded into the common bile duct and can obstruct the common bile duct.
A typical feature of biliary pain is epigastric or right upper quadrant pain that often radiates to the back or to the right shoulder blade associated with nausea or flatulence. These symptoms mimic the pain of IBS or peptic ulcer disease or even cardiac ischemia. If examinations carried out at a time when the patient has symptoms, tenderness in the right upper quadrant may be a useful sign.
The pain of biliary colic can be quite characteristic. It is often very memorable, very severe, and it rises to a crescendo and plateaus for about 30 minutes or so before diminishing again. Patients may have episodes of these pains and may be able to recall the episodes quite succinctly. These characteristic symptoms would point to a biliary cause for the patient's pain. If the patient just complains of a vague, generalized pain in the right upper quadrant this is usually not caused by biliary colic and removal of the gallbladder with or without stones usually is unproductive.
When stones dislodge into the common bile duct, then abnormal liver function tests (LFTs) may result with or without a rise in serum bilirubin; but when obstruction gets complete, then jaundice is inevitable. Sometimes stones impacted in the neck of the gallbladder can cause local edema, which can compress on the common bile duct and cause a degree of jaundice or abnormal LFTs. This is sometimes referred to as Mirizzi's syndrome.
Pain of an inflamed gallbladder is usually a constant right upper quadrant pain and can be exquisitely tender on palpation.8
The best way of imaging a gallbladder is to perform an ultrasound scan. A well-performed ultrasound scan is usually very instructive. A well-fasted patient will have a distended gallbladder and gallstones usually cast an acoustic shadow giving characteristic pictures. The size of the common bile duct may also be measured and it should be no more than a few millimeters. Anything in excess of 6 mm usually suggests some ongoing pathology although the size of the duct will be dilated after cholecystectomy and becomes increasingly dilated with advancing age.
If other lesions are suspected, then a computed tomography (CT) scan would be a very useful investigation as it would likely image the pancreas rather better than an ultrasound scan. If stones in the common bile duct are suspected either from raised LFTs or if there is a dilated common bile duct without obvious stones, then it is reasonable to proceed to magnetic resonance cholangiopancreatography (MRCP), which is valuable in assessing the presence of common bile duct stones. The presence of common bile duct stones will require therapy with endoscopic retrograde cholangiography (ERCP) (Figs. 1.8 to 1.10).
Adenomyomatosis of the Gallbladder
Ultrasound scan can often pick up cholesterol accumulation in the gallbladder known as cholesterolosis and may also be associated with adenomyomatosis. This is a benign condition characterized by hyperplastic changes of the gallbladder wall, causing overgrowth of mucosa, thickening of muscle wall and formation of intramural diverticula or sinus track sometimes known as Rokitansky–Aschoff sinuses. It may be seen on ultrasound scan as a tumor-like lesion but these are completely benign.
zoom view
Fig. 1.8: Ultrasound showing gallstones: note the acoustic shadows cast by the stones.
zoom view
Fig. 1.9: Magnetic resonance cholangiopancreatogram (MRCP) showing three stones in the common bile duct as well as stones in the gallbladder.
zoom view
Fig. 1.10: Endoscopic retrograde cholangiopancreatography showing biliary duct stones.
Occasionally, ultrasound scan cannot differentiate between adenomyomatosis and gallbladder cancer and further imaging may be considered including MRI or CT scanning.
About 15% of the British adult population have gallstones. Hence, it is not uncommon to have patients presenting with right upper quadrant pain and found to have incidental gallstones, but the presence of gallstones does not necessarily mean that they are the cause of the patient's symptoms. If the patient has a definite acute cholecystitis, then there would be evidence on ultrasound scan of a thickening gallbladder. Then it is almost certain that the pain experienced would be related to the gallbladder and cholecystectomy would be the correct treatment option. Often patients present with more 10diffuse symptoms and therefore endoscopy is often required to make sure that there are no other upper GI causes of the pain and symptoms before considering cholecystectomy on the patient. Because the symptoms may not be related to the gallbladder and may really reflect underlying functional problems in many patients, as many as 40% still continue to have symptoms despite a cholecystectomy. Hence, it is important to get an accurate reliable history before proceeding to cholecystectomy. Additionally, it must be noted that the absence of a gallbladder carries with it its own problems. This is sometimes referred to as postcholecystectomy syndrome and includes biliary gastritis, reflux symptoms and diarrhea. Diarrhea is caused by unbuffered bile reaching the colon and irritating the colon.
Is it a Pancreatic Disease?
The pancreas is a difficult organ to investigate. It lies behind the duodenum and the stomach and therefore ultrasound scans can be unreliable because of overlying gas. Upper GI endoscopy only reveals gastric and duodenal mucosa and unlikely to pick up evidence of pancreatic disease. The vast majority of patients with epigastric pain will have functional bowel pain and not necessarily underlying pancreatic disease. A high index of suspicion of neoplastic disease is necessary if one is to avoid the common mistake of missing early and therefore treatable pancreatic lesions. Pain from the pancreas can be quite diverse. Pain arising from the head of the pancreas may cause a right upper quadrant type pain and sometimes radiating to the back. Lesions in the body are frequently epigastric and more likely to radiate to the back and lesions in the tail may present as left upper quadrant pain. Initially, pain may be provoked by meals, particularly meals high in fat content but gradually it will be more severe, constant and patients are often more comfortable sitting forward rather than lying on the back.
Biochemical Tests for Pancreatic Disease
Serological markers such as CA19-9 detect carbohydrate antigens expressed by mucus glycoproteins. When ducts of the pancreas are blocked, these mucus glycoproteins spill into the blood circulation and can be detected in very high levels in the blood. Hence, the very high levels of CA19-9 may indicate pancreatic tumor. However, the test is nonspecific and there are many other causes of elevated CA19-9. Any other mucus-secreting tumor or ascites may also cause a raised CA19-9. However, presence of raised CA19-9 would trigger the need for more radiological imaging of the pancreas.
An ultrasound scan performed by a good operator in a non-gaseous abdomen can pick up pancreatic lesions. However, CT scans are more reliable. CT scans 11would show a pancreatic lesion and also help stage the lesion. Size of the lesion is perhaps less important than the invasion of the lesion into neighboring vascular structures like the superior mesenteric artery and portal vein, which would severely compromise the ability for the surgeon to do a curative resection.
When the pancreatic lesion is in the head of the pancreas, the patient often presents with jaundice as a result of obstruction of the common bile duct. Once again a CT scan is helpful in staging the disease and making a diagnosis. An endoscopic ultrasound is also very helpful in further staging of disease, especially when it is in the head or the neck of the pancreas. Lesions in the tail of the pancreas are less accessible to endoscopic ultrasound (Figs. 1.11 to 1.17).
zoom view
Fig. 1.11: Computed tomography of an inflamed swollen pancreas: This patient had azathioprine-induced pancreatitis.
zoom view
Fig. 1.12: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas are potentially malignant intraductal epithelial neoplasms that are composed of mucin-producing columnar cells often present as incidental findings on scanning. The MRI shows a grossly dilated pancreatic duct.
zoom view
Fig. 1.13: Computed tomography scan showing dilated intrahepatic ducts and a pancreatic head tumor.
zoom view
Fig. 1.14: Percutaneous transhepatic cholangiogram (PTC) showing dilated intrahepatic ducts and a tumor obstructing the lower end of common bile duct.
Is there an Intestinal Disease?
Pain arises from intestinal disease usually arises either from contractions of the intestine (colic) or due to distention of the bowel. Colicky-type abdominal pain can arise spontaneously as in IBS or as a result of an obstruction caused by a stricture. Because IBS is so common, in the absence of any “red flag” symptoms, it is wise to make a firm diagnosis of IBS rather than embark on expensive and sometimes unpleasant investigations. In patients without any of these alarming symptoms, a negative CRP, blood count and fecal calprotectin would exclude the majority of organic diseases and enables the physician to confidently make a diagnosis of IBS. A simple algorithm is found in Figure 1.2.13
zoom view
Figs. 1.15A and B: Pancreatic tumor with dilated intrahepatic ducts. (A) Transverse and (B) Coronal images of tumor.
zoom view
Fig. 1.16: Magnetic resonance imaging showing chronic pancreatitis with dilated pancreatic duct.
zoom view
Fig. 1.17: Magnetic resonance imaging showing marked thickening of the terminal ileum with surrounding inflammation: This is typical of terminal ileal Crohn's disease.
In a younger patient with symptoms of abdominal pain with weight loss, mild anemia or positive fecal calprotectin, always suspect inflammatory disease of the bowel like Crohn's disease. If there is associated rectal bleeding or diarrhea, it could suggest colonic involvement with inflammatory bowel disease, either ulcerative colitis or Crohn's disease. In general, ulcerative colitis, being a mucosal disease, does not result in abdominal pain except when there is a complication like perforation or megacolon. Crohn's disease being a transmural disease can cause irritation of the parietal peritoneum and therefore pain is often a predominant feature.
In the older patient presenting with any of these symptoms, the principal condition to exclude is colonic neoplasia. Some form of imaging is therefore necessary in both groups of patients.
Colonoscopy is by far the best imaging modality as it would pick up any colonic neoplasia and the majority of patients with colonic or ileocolonic inflammatory bowel disease. A skillful colonoscopist should be able to enter the terminal ileum and assess the terminal ileum in over 90% of patients. Inflammatory changes in the colon are very common in patients with Crohn's disease, even in those with predominant ileal disease. If the patient is unable to have a colonoscopy for whatever reason, then the alternative is CT colography or MRI scanning. In patients where colon cancer is being suspected, particularly the older age group, CT colography can be a useful alternative to colonoscopy. It may be an alternative in individuals for whom colonoscopy is deemed too invasive, especially in the frail elderly patient. There are limitations to CT colography. Polypoidal lesions can be difficult to differentiate from particulate feces and it is clearly not possible to carry out biopsies and histological examination of any lesions seen. Often when 15a lesion is suspected or found the individual will need a colonoscopy eventually. There is also an issue of radiation exposure and therefore colonoscopy is still regarded as the investigation of choice. MRI scanning is also valuable. It is particularly useful in detecting small bowel Crohn's disease, especially in parts where the colonoscope is unable to reach. A modified way of performing an MRI with the ingestion of a polyethylene glycol drink allows imaging of the small bowel with contrast (magnetic resonance enterography; MRE). This will pick up areas of intestinal stenosis caused by inflammation and also fissures and ulcerations of the mucosa. MRE also gives a good impression of the thickness of the bowel, another indication of infiltrative or inflammatory condition. A standard CT of the abdomen is also a valuable investigation. It has the advantage of being somewhat cheaper than MRI and it can show quite a lot of detail. It will also show the presence of abscess formation or diverticular disease of the colon. Finally, if lymphoma is suspected, a CT scan of the abdomen would pick up associated lymphadenopathy, which usually is generalized and may be associated with splenic enlargement (Figs. 1.17 to 1.21).
Is it Volvulus or Intussusception?
Occasionally, patients may have intermittent severe pain due to intermittent volvulus. If volvulus is suspected, a plain X-ray is often very helpful (Fig. 1.22). Gastric volvuluses can be picked up and are often associated with a large diaphragmatic defect and a chest/upper abdominal film would be quite revealing. A volvulus affecting the sigmoid would present with constipation and abdominal distention and often a large “coffee bean” shadow on the abdominal film is seen (Fig. 1.23).
zoom view
Fig. 1.18: Colonoscopic findings of deep fissuring ulcers with skip lesions favor a diagnosis of Crohn's disease.
zoom view
Fig. 1.19: Sigmoid inflammation. Thickened sigmoid colon clearly demonstrated by CT.
zoom view
Fig. 1.20: Extensive mucosal inflammation and edema: This patient has raised peripheral eosinophil count and should alert the clinician to possible eosinophilic enteritis.
zoom view
Fig. 1.21: Eosinophilic infiltration of colon suggests a diagnosis of eosinophilic enterocolitis.
zoom view
Fig. 1.22: Large hiatus hernia. Much of the stomach is in the chest.
zoom view
Fig. 1.23: Sigmoid volvulus. Massively dilated sigmoid colon giving the “coffee bean” sign.
Both problems may be intermittent and may present acutely as a surgical emergency but sometimes may be chronic and persistent or even be asymptomatic (Figs. 1.24A and B).
Is it Mesenteric Ischemia?
Mesenteric Ischemia should be considered in an older patient. It can present acutely as an area of bowel infarction. This can occur after an episode of hypotension when areas of vascular watershed like the splenic flexure of the colon can become ischemic. Patients may present with pain, rectal bleeding with or without diarrhea. Acute intestinal infarction can also occur in patients with embolic disease like atrial fibrillation. Atheromatous diseases tend to present with chronic intestinal ischemia with a chronic pain often 18associated with food and eating, sometimes referred to as intestinal angina. These patients therefore reduce their food intake and can lose weight quite dramatically. A good history is the key. It is strongly associated with smoking and diabetes and they often have evidence of arteriopathy elsewhere, like peripheral vascular disease or ischemic heart disease. It can be extremely difficult to diagnose, CT may show calcified vascular atheroma. MRI angiography can be helpful in this situation, confirmation and treatment requires direct angiography and angioplasty can be attempted.
zoom view
Figs. 1.24A and B: Gastric volvulus. (A) The gastrografin meal shows a gastric volvulus flipped along its axis (organo-axial volvulus); (B) CT image shows the same.
Is it Diverticular Disease?
Diverticulosis of the colon is extremely common. Like gallstones, it is easy to attribute symptoms to diverticular disease but they may not necessarily be the cause of the patient's complaint. Diverticular disease is easily picked up on barium enemas, abdominal CTs or colonoscopy. Typically, diverticulosis causes few symptoms. However, when they get inflamed (diverticulitis) 19they can cause discomfort, pain and altered bowel habit. The pain is usually in the left iliac fossa as the commonest site of diverticular disease is in the sigmoid colon.
Is there an Underlying Metabolic Disease?
Metabolic diseases are rare. However, physicians should always be alert to a possibility in unusual presentation of organic diseases suspected and none found. Hypercalcemia and porphyria are metabolic diseases that can present as abdominal pain. In the case of hypercalcemia, serum calcium is easily checked by chemical profile. Hence, it is important to cast an eye on the calcium level when attending to a patient with abdominal pain. In hypercalcemia, pain can be caused by acute as attacks of acute pancreatitis or chronic pain due to dyspepsia or ulcer disease caused by hypersecretion of acid. This is due to the raised serum gastrin found in patients with hypercalcemia. The helpful aide memoire: “stones, bones and abdominal groans” summarizes hypercalcemia with renal stones, bone lesions and abdominal pain. Hyperlipidemia syndromes may also present with acute abdominal pain because it can cause attacks of acute pancreatitis.
Porphyria can cause abdominal pain. Acute intermittent porphyria, porphyria variegata but not porphyria cutanea tarda, can cause acute intermittent episodes of severe abdominal pain rather than chronic pain. There may be neurological complications such as behavioral disturbances, epilepsy, coma or peripheral neuropathy. During an acute attack of hyponatremia; hypertension and uremia are common. Other rare causes of abdominal pain include lead poisoning, C1 esterase inhibitor insufficiency, familial Mediterranean fever and neurological conditions like multiple sclerosis and peripheral neuropathy. Abdominal pain is also a common problem in patients with longstanding diabetes. They are at increased risk of gallstones, duodenal ulcer disease, intestinal vascular insufficiency and pancreatitis.
A high index of suspicion and the specific diagnostic test is required to make the correct diagnosis.
Is there an Occult Malignant Disease?
If the patient remains unwell with persistent pain, there is always a lingering worry that malignant disease may have been missed. The next step would be a review of all the investigations carried out to date making sure that there are no gaps left unplugged. Abdominal CT scan is probably the best investigation to exclude intra-abdominal malignancies and if in doubt should be reviewed by an experienced radiologist. Colonoscopy remains the best investigation for colonic neoplasia but occasionally it may be missed because of a bad prep or incomplete examination. Hence, a review of the colonoscopy and a repeat procedure by an experienced endoscopist should be considered if there is a high degree of clinical suspicion. If there is still some doubt, then a “wait and 20see policy” or an interval CT scan, perhaps 2 or 3 months down the line would be helpful, but with modern imaging it is rare to miss lesions unless they are extremely small or elusive. Finally, in patients where the diagnosis remains elusive and the suspicion is still high, a laparoscopy may be considered, but it would be unusual to resort to such invasive measures (Figs. 1.25 and 1.26).
zoom view
Fig. 1.25: Renal cancer: This is most often picked up incidentally by ultrasound.
zoom view
Fig. 1.26: Renal cell cancer on CT scanning.
Is it Endometriosis?
Lower abdominal and pelvic pain associated with hemorrhagic phase of the menstrual cycle is suggestive of endometriosis. Up to 25% of these patients may have bowel involvement and that often results in abdominal pain. The endometriosis tends to occur on the serosal surface and bleeding into the gut is really quite rare. Endometriosis can cause stricture and adhesions and sometimes mistaken for neoplastic disease or Crohn's disease. 21Laparoscopy usually is diagnostic and treatment with cauterization is possible laparoscopically.
Irritable Bowel Syndrome
Natural History
Irritable bowel syndrome should be considered as one of a group of functional GI conditions that occur throughout the elementary tract. It is by far the commonest of the functional GI diseases. It can be very varied in presentation and can mimic serious organic diseases. It is very troublesome to the sufferer and can be challenging to manage.
Symptoms: The cardinal symptom that most patients complain of being abdominal pain. There may be continuous dull ache but most frequently it is a colicky-type abdominal pain that comes as spasms lasting only a few minutes or several hours. The site of the pain can be very variable, often flitting, but sometimes predominantly in an area typically the left iliac fossa or the right iliac fossa. When asked to point where the pain is, patients often move their hands in a circular fashion over the abdomen suggesting a varied or diffuse site. Along with the pain, the two other principal symptoms are abdominal bloating/distention and a change in the bowel habit. This can vary from predominant constipation to predominant diarrhea or a mixture of constipation alternating with diarrhea. Definitions of IBS have been proffered and it can be quite difficult to pin down precisely. For the purposes of clinical trials, strict definitions are required and several have been devised. The Rome III criteria (Rome Foundation for Functional GI Diseases) included recurrent abdominal pain or discomfort for 3 days out of a month in the past 3 months associated with two or more symptoms which include:
  • Improvement with defecation
  • Onset associated with change in stool frequency
  • Onset associated with change in stool form.
This definition is rather loose and all-encompassing and has since been replaced by Rome IV in 2017. NICE (National Institute of Clinical Excellence) offered an alternative, simpler definition that is more suitable for everyday clinical use and the definition is:
Abdominal pain/discomfort relieved by defecation or associated with altered stool frequency/form plus 2 or more of:
  • Altered stool passage
  • Abdominal bloating/distention
  • Symptoms made worse by eating
  • Passage of mucus.22
From a clinical point of view, the patients presenting with the classic pattern of abdominal pain associated with bloating and a change in bowel habit are usually easy to pick out and patients with predominant constipation or alternating constipation and diarrhea probably require no further investigation. However, patient with persistent diarrhea would probably benefit further investigation to detect cases of small intestinal bacterial overgrowth, bile salt diarrhea and microcytic/collagenous colitis.
Psychology: Anxious obsessional patients are certainly more likely to consult a doctor if they develop IBS, but the psychological aspects of this condition are probably over emphasized. Many patients who are psychologically normal to have this syndrome. It is true that patients will often bring out stress as a major trigger for their symptoms. However, it would be a mistake if the physician overemphasized that aspect and deprive the patient of simple treatments that might improve their symptoms and overly focus on the psychological aspects. Suggesting that the condition is all in the mind is likely to upset the patient and create barriers between physician and patient.
Epidemiology: A survey has shown that over 14% of apparently healthy British subjects have IBS by the ROME 1 criteria. Furthermore, over half the patients attending British gastroenterology clinics have a predominant functional bowel problem. Although 65% are women, an increasing number of young men also suffer from this condition. In many of these patients, the problems are longstanding and when questioned, these patients would often have a very long history starting from early adulthood or childhood.
Etiology and Pathogenesis: This syndrome has many complex and contributory factors. Looking at the predominant symptoms in turn.
Abdominal Pain: The mechanism of abdominal pain is complex. There is good evidence that patients with IBS have increased visceral sensitivity. Inflating a balloon in the rectum of a patient showed that they experienced discomfort at lower volumes than normal subjects. There is also evidence that patients with IBS handle pain abnormally. This probably occurs at the modulation level in the spinal cord. In patients with postinfective IBS, there is also microinflammation and inflammatory cells may release pain causing chemicals at the nerve endings.
Bloating: Bloating is a very common symptom of IBS. Its etiology is also quite complex. There is evidence for abnormal gas handling. The tone of the bowel may be altered causing gas to be trapped in parts of the bowel and there may be altered gas production as well. Altered gas production may be due to bacterial fermentation processes. In patients where there is small bowel bacterial overgrowth, there is increased gas production in the small bowel. Patients who are intolerant of carbohydrates and also with celiac disease may also have abnormal gas production due to poorly digested sugars fueling colonic bacterial fermentation. Furthermore, ingestion of fermentable carbohydrates 23is also a possible source of gas. Patients with slow gut transit found in those with predominant constipation will also get abdominal distention from fecal loading. Finally, some hormones, particularly estrogens, can cause abdominal bloating. However, all the causes of gas production above does not account for the degree of distention that many patients display. It also does not account for how quickly the distention can occur and regress in the course of a day. It is now known that the most important contributor to bloating is phrenic dyssynergia. This occur when the diaphragm is contracted unconsciously, and simultaneously the abdominal wall muscles to relax. The cause for this is still unknown (Fig. 1.27).
Change in Bowel Habit: A change in bowel habit is characteristic of IBS. Thus, IBS may be classified as being IBS-D when there is predominant diarrhea, IBS-C when there is predominant constipation and IBS-M when there is an alternating or mixed picture. The etiology is complex and probably multifactorial. The change in motility of the gut may be a result of delayed gastric emptying, small bowel or colonic transit changes. This is often triggered by food or emotion. In a number of patients, there is also evidence of small bowel bacterial overgrowth.
The stool type correlates very well with gut motility and the Bristol Stool Chart has become a very useful visual aid in clinics for patients to point out which type of stools they have. Stool types 1 and 2 (Fig. 1.28) are associated with constipation and the gut transit is slow, whereas patients with Bristol types 6 and 7 have rapid gut transit and diarrhea.
Postinfective Irritable Bowel Syndrome: In a number of patients presenting with IBS, there is a clear history of an infective episode prior to the onset of IBS symptoms. There will be a history of some kind of infectious diarrhea whether or not a pathogen becomes cultivated. During the acute episode, there is usually diarrhea plus vomiting, rather than diarrhea alone.
zoom view
Fig. 1.27: Bloating: It is a combination of gas as diaphragmatic contraction and relaxation of abdominal wall muscles.
zoom view
Fig. 1.28: Change in bowel habit.
The patients then start having episodes of the typical IBS that lasts long after the acute episode. There is a predominance of diarrhea (IBS-D) as opposed to the constipation or alternating type. There is often a higher anxiety score prior or during the infection. Patients often acquire the infection while travelling, often on holiday or away from home.
Algorithm for Diagnosing Irritable Bowel Syndrome: It is important to make a firm diagnosis of IBS early without recourse to complex and unpleasant investigations. NICE has issued a set of guidelines that are quite helpful. If the patients do not have alarm symptoms and have the typical symptoms outlined above, then a firm diagnosis of IBS can be made. The alarm symptoms include:
  • Age (>40)
  • Strong family history of colorectal cancer/IBD
  • Rectal bleeding
  • Anemia
  • Weight loss
  • Abdominal mass.
In this group, only a simple noninvasive test is required. Blood tests including a full blood count, biochemistry, CRP and thyroid function test along with celiac antibodies can be carried out. Stool tests, including fecal calprotectin and culture if there is the reason to suspect an infective cause. If diarrhea is predominant, a hydrogen or methane breath test can be very helpful. This detects the presence of small bowel bacterial overgrowth that ferments glucose or lactulose and releases hydrogen or methane in the breath. The test is simple and relatively cost-effective. Fecal calprotectin or lactoferrin is emerging as a very helpful test in this situation. Calprotectin and lactoferrin are released by inflammatory cells into the GI tract and this is excreted in the feces and easily detected. When there is inflammation, the level of fecal calprotectin 25rises exponentially. Laboratory standards vary, but any fecal calprotectin over 50 µg/g of feces is usually indicative of possible inflammatory bowel disease. However, a negative calprotectin does not exclude other organic diseases or indeed Crohn's disease in remission. A simple algorithm is shown in Figure 1.2.
Abnormal Bile Salt Handling: Nearly 30% of patients with IBS have been found to have abnormal bile salt handling. When bowel salts are not reabsorbed in the terminal ileum then some gets into the colon and that irritates the colon and can cause diarrhea-predominant symptoms. It is possible to carry out a SeHCAT scan. This, however, can be quite expensive. Empirical treatment with cholestyramine is safe and cheap and should be tried in patients with diarrhea-predominant IBS.
Often doubt still exists as to whether or not the patient has inflammatory bowel disease and probably the single most useful investigation in this situation is to perform a colonoscopy. For patients with diarrhea-predominant symptoms, inflammatory bowel disease can be difficult to exclude. Patients with microcytic and collagenous colitis can be very difficult to diagnose without endoscopic examination and may have negative fecal calprotectin and ultimately can only be diagnosed with biopsies, particularly of the right colon.
Reassurance: The most important part of management of IBS is reassurance. Make a firm diagnosis and explain that it is a benign condition. The mechanisms of pain and altered bowel habit in a healthy intestine should be explained simply and clearly to the patient. It should be made clear that the doctor understands the severity and genuine nature of the patient's symptoms and that the patient can be reassured that the condition is not harmful and the frequency and severity of symptoms would diminish with time. Treating the patient dismissively as a neurotic will lead the patient to assume that symptoms have not been taken sufficiently seriously. This will increase any cancer phobia and the patient will almost certainly seek a second opinion.
Having established a rapport, the physician should look at exploring some of the triggers. If there is evidence of an infective trigger, then probiotics may be proffered although clinical trial evidence for its use is sketchy. If there is a degree of stress or anxiety involved, that should be addressed at a suitable time. Other psychological treatments like hypnotherapy and counseling have a place if available.
Dietary Advice: Dietary advice or dietetic referral may be helpful. It is directed at specific symptoms.
Constipation: Patients with predominant constipation should be encouraged to eat more foods containing soluble fibers. This is found in many foods like fruit and cereals.26
Diarrhea: Diarrhea can be more difficult to treat with dietary measures. Avoidance of certain foods like dairy and gluten may be important. Even patients without celiac disease may have poor carbohydrate handling and gluten intolerance and it is well worth trialing them on a gluten avoidance diet.
Bloating: Foods that produce a lot of gas are the ones that are fermentable. A group of foods known as FODMAP (Fermentable Oligo-Di-Mono-saccharides and Polyols) are shown to produce more gas and therefore abdominal distention. Avoidance of these foods can be difficult as they are very varied but a session with a dietitian can be very helpful.
Pharmacological Treatments: Once a patient is reassured that the condition is benign, it is important then to explain that you have means of treating the specific symptoms. Abdominal pain can be treated with antispasmodics like mebeverine, hyoscine and alverine. If the pains are spasmodic and episodic then patients can have these drugs on demand rather than on a maintenance fashion. If the pain is more constant then treatment with a small dose of a tricyclic like amitriptyline has been shown to be effective although tricyclics tend to cause constipation and therefore best avoided in patients with constipation-predominant irritable bowel. Conversely, tricyclics can be very helpful in patients with diarrhea-predominant IBS. An alternative to tricyclics are the selective serotonin reuptake inhibitors (SSRIs). They tend to cause diarrhea probably a better drug to try on patients with constipation-predominant IBS. It is important to emphasize that you are using the drugs to control the symptom not because you think they are depressed as such.
Newer drugs have been recently evaluated for use in IBS with constipation. For IBS-C linaclotide have recently been introduced. A longer discussion of these drugs on constipation is in the Chapter 4. For IBS-D, symptomatic treatment with loperamide is helpful and new agents like eluxadoline have been recently approved for this indication. Rifaximin, a poorly absorbed antibiotic, has also been approved for IBS-D (see Chapter 3).
Patients with evidence or suspicion of bile salt malabsorption could be given a trial with cholestyramine. Bile excretion is maximal in mornings, so this is best given first thing in the morning, 30 minutes before breakfast. If there is evidence of small intestinal bacterial overgrowth, antibiotic therapy, notably with rifaximin, could be given.
Duodenal Ulcer
Natural History
Diagnosis: The principal means of diagnosing duodenal ulcer disease is endoscopy. However, if patients present with dyspeptic symptoms it is not unreasonable to perform a test for H. pylori on the onset. The noninvasive 27methods of testing for H. pylori are cheap and that could be serology, breath testing or fecal antigen testing. The latter has increasingly gained acceptance as being both sensitive and specific. The presence of H. pylori in a symptomatic patient would justify H. pylori eradication. This “test and treat” method has gained general acceptance in recent years.
Symptoms: The symptoms of duodenal ulcer disease can be rather non-specific. Duodenal ulcers may be completely asymptomatic and it is not uncommon for patients to be admitted to hospital with a bleeding ulcer and give no history of previous dyspepsia. The most common symptom is epigastric pain that wakes the patient at night and periodic pain. Periodic pain refers to relapses of pain lasting several days or weeks interspersed with pain-free periods for weeks or months. Less reliable association is relief of pain with antacids or food. Major complications of duodenal ulcers are perforation and bleeding and in the elderly and patients with multiple comorbidities like cardiac, renal failure and malignancy, it carries a significant mortality rate.
Epidemiology: Previous epidemiological studies have shown that as many as 9% of women and 12% of men have been told they have a diagnosis of duodenal ulcer disease at some point. However, the discovery that H. pylori is a major cause of duodenal ulcer disease has led to eradication of the bacteria. This has completely altered the natural history of the disease from a recurrent condition to permanent cure. Furthermore, as the prevalence of H. pylori infection decreased in many Western nations, so has the prevalence of duodenal ulcer disease. However, there is an increase in incidence of nonsteroidal-induced peptic ulcer disease particularly in elderly patients. Smoking is strongly associated with duodenal ulcer disease as is alcohol.
Etiology and Pathogenesis: H. pylori infection and NSAIDs are the main etiological causes for duodenal ulcer disease. The mucosa of the stomach and duodenum need to defend itself against the effects of pepsin and acid. Mechanisms in which there is increased acid and pepsin action and reduced defenses by the duodenal mucosa would result in mucosal ulceration and breakdown. Defects in the healing and repair mechanisms are also contributory factors. Smoking and stress can elevate basal acid output, reduce mucus synthesis and inhibit healing.
Drugs like the anti-inflammatory drugs and aspirin cause ulceration either by direct toxic effects or inhibit prostaglandin synthesis by binding on cyclo-oxygenase (COX) active site (specifically COX-1). Aspirin even in low doses can cause ulceration by direct toxic chemical effects on the mucosa itself. Nonsteroidals drugs, however, tend to act by inhibiting prostaglandin synthesis. Prostaglandin depletion causes an increase in acid secretion, 28decreased mucin production and a decrease in bicarbonate secretions, all factors vital in promoting ulcer formation. Prostaglandin is also important in epithelial cell healing and therefore nonsteroidal drugs also reduce the ability of the mucosa to repair itself. Additionally, the analgesic effects of non-steroidal drugs may account for the fact that many nonsteroidal-induced duodenal ulcer disease remain silent and may not present until bleeding or perforation occurs (Fig. 1.29).
zoom view
Fig. 1.29: Histology of gastric ulcer margin.
Helicobacter pylori: H. pylori remains the major cause for duodenal ulcer disease and worldwide it is a massive health problem. It is strongly associated with duodenal ulcer disease but the most convincing evidence is the fact that when eradication of the bacteria is successfully achieved a cure results. However, the bacterium is very common and the majority of people harboring this bacteria in the stomach do not have duodenal ulcer disease or come to any apparent harm. The bacterium is a gram-negative rod and resides in the deep portions of the mucus, generally in the gastric mucosa. It is uniquely adapted to this hostile environment. It has multiple flagella that helps in motility and adhesion and produces very strong urea enzyme. This produces ammonia from urea which is alkaline and helps to neutralize any acid diffusing into the mucus layer.
The infection is probably acquired during childhood and spreads in areas and times of overcrowding. Initially, the bacterium tends to inhabit the antrum of the stomach and over time tend to migrate proximally. Apart from duodenal ulcer disease, H. pylori infection is credited to cause gastric ulcers, MALT lymphomas and gastric cancer. It is still not understood as to how the bacterium can cause the diverse pathology and yet, in a large number of individuals, it causes no symptoms or pathology at all. It is likely to be a combination of bacterial and host factors. The bacteria may have genetic determinants that result in increased pathogenicity. This includes 29its ability to produce certain enzymes like VacA and CagA or may have adhesins which facilitate attachment of the bacteria to the gastric epithelial cells. Amongst host factors may be the subject's ability to mount an inflammatory response and the specific site of the stomach where the bacteria tend to colonize.
zoom view
Fig. 1.30: Putative pathogenesis of H. pylori diseases.
Patients who predominantly have antral inflammation would lead the antral G cells to produce high levels of gastrin via the loss of negative inhibition from the D cells in the antrum. The result is an elevated gastrin level that stimulates the acid secreting parietal cell to secrete more acid. Patients who have predominantly body and fundus infection with H. pylori may find that the parietal cells themselves get affected and acid level output may actually be reduced. This may lead, in the long term, to chronic atrophic gastritis eventually leading to intestinal metaplasia, dysplasia and leading to gastric cancer. In the majority of patients with pangastritis, the infection tends to be non-pathogenic and therefore the bacterium inhabits the individual without producing any symptoms or disease (Fig. 1.30).
Management of Duodenal Ulceration
The management of duodenal ulcers has altered dramatically over the last 30 or 40 years. Operations frequently performed for duodenal ulcers in the past have given way to highly effective acid suppressing drugs like H2 antagonists and then followed rapidly by even more powerful acid suppressants like PPIs. H. pylori eradication has changed the natural history of the disease. However, increased bacterial resistances to antibiotics have hindered effective H. pylori eradication in many parts of the world.30
H2 Antagonists and Proton Pump Inhibitors: H2 antagonists like cimetidine and ranitidine are safe and effective drugs for reducing gastric acid secretion and are now found in many over-the-counter medications for dyspepsia. They do heal duodenal ulcers by suppressing acid by inhibiting the H2 receptors, one of the three receptors that cause the parietal cell to secrete acid. The other two receptors are acetylcholine receptor and gastrin receptor. Hence, it only partially inhibits the excretion of acid. The final pathway is the migration of the “proton pump” which is ATPase. This migrates to the canaliculus membrane and the pumping of a hydrogen ion (Proton) accompanied by potassium chloride that leads to the production of hydrochloric acid. This is pumping against a huge concentration gradient and acquires energy that is supplied in the form of the breakdown of ATP into ADP.
Inhibitors of the proton pump include omeprazole, esomeprazole, lansoprazole, pantoprazole and rabeprazole. Thus, almost complete blockage of acid secretion is the result. These drugs also have a long biological life as the inhibition is irreversible and parietal cells have to manufacture new proton pumps to replace those blocked. Ranitidine in clinical trials has shown to heal up to 70% of duodenal ulcers at 8 weeks whereas PPIs would heal duodenal ulcers at > 90% at 8 weeks. However, unless the underlying cause for the ulcers (e.g. H. pylori and nonsteroidal drugs) is removed then the ulcers would tend to recur (Fig. 1.31).
zoom view
Fig. 1.31: Parietal cell function: The gastric parietal cells are the producers of acid in the stomach. Gastrin acetylcholine and histamine receptors are present in the inner membrane where hormonal (gastrin), neural (vagus nerve releasing acetylcholine) and inflammatory (histamine) stimuli activate the proton pump ATPase. Inhibition of this enzyme stops parietal cell acid production.
Anti-Helicobacter Therapy: Eradication of H. pylori will result in curing of H. pylori-associated duodenal ulcer disease. As this accounts worldwide for the majority of duodenal ulcer cases effective H. pylori eradication is much sought after. The typical regime would be a “triple therapy,” which comprises of a PPI like omeprazole or lansoprazole with two antibiotics typically a combination of either clarithromycin or amoxicillin or metronidazole or tinidazole. The treatment is usually carried out for 14 days. Shorter regimes tend to be less effective and promote bacterial resistance. Even with 14-day triple therapy eradication may not exceed 70% and may be even lower in parts of the world where antibiotic resistance is common. Hence, in refractory cases other treatment strategies have been sought. One strategy is quadruple therapy with the addition of bismuth in the form of tripotassium dicitratobismuthate. Other regimes have also been recently trialed. One particular promising regime is “sequential therapy” that usually takes the form of 5 days of lansoprazole and amoxicillin followed by 5 days of lansoprazole, clarithromycin and metronidazole.
Failure to Heal: A repeat endoscopy to check for healing is not usually necessary. Effective H. pylori eradication can be checked either by using urea breath tests or fecal antigen tests, both of which are equally reliable. However, if the patient remains symptomatic it may be necessary to re-endoscope such patients. If patients are compliant with treatment and H. pylori eradication is confirmed then one would also have to question whether patients have been taking aspirin or nonsteroidal agents. Rare conditions such as Zollinger–Ellison syndrome should also be considered. Effective treatment with H. pylori eradication should result with an effective cure. However, in some patients the H. pylori may be resistant to therapy. In a few patients, it would be necessary to be placed on maintenance therapy with PPIs.
Surgery: Surgery for duodenal ulcer disease thankfully is extremely rare nowadays. Operations are usually now reserved for complications such as bleeding and perforation. The operations performed are mainly of historic interest but there remain some patients from the “pre-Helicobacter discovery era” who may have had such procedures carried out on them (Fig. 1.32).
Duodenitis is often reported in endoscopy reports for endoscopies carried out for dyspeptic symptoms. However, there is a very poor correlation between symptoms and endoscopic appearances. Even endoscopic and histological appearances are poorly correlated. Many asymptomatic patients may have duodenitis as incidental endoscopic findings. However, it is clear that H. pylori infection in the duodenum often leads to gastric metaplasia. This occurs when gastric type mucosa starts proliferating in the duodenum.32
zoom view
Fig. 1.32: Surgical procedures for ulcer diseases.
Gastric metaplasia may also be caused by increased acid secretion. Non-steroidal drugs and aspirin are also implicated in causing duodenitis. Duodenitis is also strongly correlated with smoking and patients with poor nutritional intake.
When widespread duodenal inflammation occurs, it is also important to consider Crohn's disease; celiac disease; Whipple's disease and small bowel lymphoma. Biopsies would be indicated if the endoscopist is unsure of the exact pathology or if these conditions are suspected. Usually, however, the inflammation is mild, confined to the first part of duodenum and is usually of little consequence to patients.
Non-ulcer Dyspepsia/Functional Dyspepsia
Natural History
The term “non-ulcer dyspepsia” is unsatisfactory with different meanings to different clinicians. The term is now largely replaced by the more useful term of “functional dyspepsia”. Fundamentally, it is presence of symptoms, such as:
  • Epigastric pain
  • Nausea
  • Bloating
  • Belching
  • Fat intolerance33
  • Heartburn
  • Early satiety.
When endoscopy is carried out it is usually normal and is thus regarded as a functional condition. There is evidence of poor pyloric relaxation and gastric emptying and there is also evidence of visceral hypersensitivity with pain or intolerance when the stomach is distended with fluid.
Due to variety of symptoms and the benign nature of the condition treatment is largely symptomatic. However, it is important to exclude H. pylori infection and if H. pylori is found then it is reasonable to give a trial of H. pylori eradication as previously discussed.
The management of functional dyspepsia includes the following:
  • If a patient has endoscopy negative upper abdominal pain and no other organic causes found either through history or by ultrasound then a diagnosis of functional abdominal pain should be made and treatment is more in line with IBS with efforts directed to control of pain and bloating. Apart from tricyclics, prokinetic agents like prochlorperazine and metoclopramide can also be helpful in this situation. The latter two drugs carry a risk of extrapyramidal side effects. Due to risks of cardiac complications domperidone use in this condition is not encouraged.
  • If heartburn is a predominant symptom, then the use of antacids and other antireflux treatments is perfectly reasonable. Use of PPI has also been shown to marginally improve symptoms in this group of patients. Even in the absence of endoscopic appearance of esophagitis, reflux can occur.
  • Diet would also play a role. Diets containing high levels of fat tend to inhibit gastric emptying and can encourage symptoms like bloating.
Zollinger–Ellison Syndrome
Natural History
In Zollinger–Ellison syndrome, there is duodenal ulceration due to increased acid production. The ulcers are multiple and usually in the distal duodenum and even in the jejunum. This syndrome is rare and probably accounts for <1 in 10,000 of all patients with duodenal ulceration but it is often left undiagnosed.
Gastrin is produced by the G cells of the gastric antrum. In Zollinger–Ellison syndrome, excessive gastrin is produced by non-beta islet cell tumors of the pancreas or duodenum. This is not under the natural feedback mechanism and leads to constant over stimulation of the parietal cells that leads to overproduction of acid. This results in hypertrophy of the gastric body and a high basal acid output. The acid is dumped into the duodenum and upper duodenum and causes ulceration.
The tumor is malignant in about 65% of patients and about 25% of tumors are sited in duodenal wall and may be very tiny and difficult to diagnose. 34However, the majority of the tumors will be found in the duodenum or the neck of the pancreas or even the porta hepatis.
Acid also inactivates pancreatic lipases and results in fat malabsorption. Diarrhea is therefore a very common symptom along with the classic symptoms of duodenal ulceration.
Diagnosis of Zollinger–Ellison Syndrome
Fasting gastrin levels is the best screening test for Zollinger–Ellison syndrome. It is also important to check the calcium levels as it may be part of a multiple endocrine neoplasia Type 1 syndrome (MEN1). Gastric acid secretion tests are rarely performed these days. In doubtful cases, a provocation test using secretin and a measurement of serum gastrin can also be helpful to make the diagnosis.
Imaging with CT scan would be necessary to locate the tumor but it is only possible to locate the tumor in 50% of the patients. Endoscopic ultrasound can also be very useful. Frequently tumors are <1 cm and easily missed on scanning. Somatostatin receptor scintigraphy (octreotide scan) is the best imaging modality. It uses radiolabeled somatostatin analog that binds to the receptors found on these tumors (Fig. 1.33). Finally, endoscopy which shows unusually severe ulceration of duodenum should alert the clinician to consider this diagnosis.
Management of Zollinger–Ellison Syndrome
The management depends on the operability of the primary secreting tumor. If it is operable then it would be considered curative. Medical therapy for controlling gastric acid output is achieved using PPIs often at higher than usual doses. In patients where surgical resection is not possible, palliative therapy with chemotherapy, interferon, and octreotide may be helpful but the response to these agents in most studies has been poor.
zoom view
Fig. 1.33: Octreotide scan. This shows a hot spot in the pancreas from a neuroendocrine tumor. Similar hot spot may be be seen in Zollinger–Ellison syndrome.
Benign Gastric Ulcer
Natural History
Symptoms: The symptoms of benign gastric ulceration are highly variable and can often be vague. Pain is usually but not always present in the upper abdomen. Usually the pain is less prominent in benign gastric ulceration than in the duodenal ulcers. Response to food is also variable, while half of the patients may get relief from eating another third may actually have pain exacerbated by food. Other symptoms include epigastric discomfort, belching, nausea and water-brash (a sudden outpouring of saliva). Patients may present with complications of gastric ulcers like bleeding and weight loss is not an uncommon symptom making it difficult to distinguish between malignant and benign conditions from symptoms alone.
Epidemiology: Gastric ulcers are less common than duodenal ulcers. In the United Kingdom as in most of Western Europe and North America, the overall incidence is decreasing but with an increasingly elderly population and a high use of nonsteroidal drugs and aspirin the incidence of complicated gastric ulcers have remained fairly constant.
Etiology and Pathogenesis: Gastric ulcers like peptic ulcer may be associated with Helicobacter infection. This is particularly true for ulcers in the prepyloric area and antrum. In the elderly population in particular, nonsteroidal agents are a major cause for gastric ulcers. Typically, they cause ulcers in the lesser curve of stomach and antrum at the junction between the antral and body-type mucosa. The inhibition of prostaglandins is likely to be the major contributory factor to these ulcers. Other contributory factors include smoking, genetic factors and poor diet. Steroid therapies are often blamed for ulcers but there is no evidence that it increases the risks of gastric ulcers but it may certainly delay healing. Ulcers associated with stress tend to be the superficial variety and can occur in severe trauma, burns (Curling's ulcers) and acute sepsis. Prophylactic use of acid suppression with PPIs may prevent these ulcers from forming.
Establish that the Ulcer is Benign: The first priority is always to establish that the ulcer is truly benign. This will require endoscopy with biopsy and possibly brush cytology if available. Biopsy should be performed even if it looks benign and after treatment at an interval of about 6–8 weeks endoscopy should be repeated to ensure complete healing. Ulcer that fails to heal adequately should be treated with suspicion.
Drug Therapy: H. pylori is implicated in about two-thirds of gastric ulcers and if it is detected eradication therapy is indicated. Details of eradication therapy 36have been discussed earlier. Gastric ulcers can take longer to heal than duodenal ulcers particularly if they are very large. Treatment with PPIs is effective and the ulcers should be reviewed with further endoscopy after 6–8 weeks of treatment to ensure complete healing. If in doubt further biopsies should be performed.
Avoidance of nonsteroidal agents would be important in patients who have nonsteroidal-induced gastric ulcers. Aspirin and antiplatelet drugs like clopidogrel should be reviewed. However, these are often prescribed for major cerebrovascular and cardiovascular indications like stroke and ischemic heart disease. The morbidity and mortality from these conditions may outweigh the risks of the gastric ulcers and therefore coprescription with PPI and aspirin together is acceptable and often results in lower overall morbidity and mortality.
Strictly speaking, gastritis should refer to histological evidence of inflammation of the stomach. Different classification exists. It can be a clinical classification based on whether it is acute gastritis or chronic gastritis, or one based on histological or endoscopic appearances, or one based on its etiology. As a result, there is no universally accepted classification system despite attempts like the Sydney Classification. Gastritis is also often reported by endoscopist based on endoscopic appearance of inflammation or redness. However, there is often no correlation between an endoscopic appearance and underlying histology or etiology of the gastric mucosal inflammation. Additionally, inexperienced endoscopists may report vascular abnormalities such as gastric antral vascular ectasia (GAVE) as “gastritis” (Fig. 1.34).
zoom view
Fig. 1.34: Gastric antral vascular ectasia (GAVE) gives an appearance not unlike a watermelon and sometimes referred to as watermelon stomach. It is often misdiagnosed as “gastritis” by inexperienced endoscopists.
Probably the best way of classifying gastritis is probably by its etiological origin.
Acute Erosive Gastritis
Acute erosive gastritis usually affects the antrum but sometimes the corpus of the stomach and occurs after major trauma, burns, sepsis, renal failure and also ingestion of alcohol, aspirin or ingestion of toxic substances. It is often asymptomatic but can cause acute upper GI bleeding. Its cause is unknown but probably related to high acid and poor cytoprotection in such patients. Management of the underlying pathology is obviously the key to prevention of acute erosive gastritis along with prophylactic use of PPIs.
Chronic Gastritis
Chronic gastritis can be broadly divided into two forms, either infectious origins or noninfectious conditions (Table 1.2).
Helicobacter-associated Chronic Gastritis
Helicobacter pylori is the principal cause of chronic gastritis, peptic ulcer disease, gastric adenocarcinoma and primary gastric lymphoma. It has a worldwide distribution and rates of infection vary between countries. The effects of H. pylori infections vary according to the site of colonization of the bacterium. There are both bacterial factors and host factors that would also decide on the final outcome of the H. pylori infection. Gastritis is almost universal. It may affect the whole stomach (pangastritis), predominant antral infection (antral gastritis) or a body type infection (corpus gastritis). When gastritis affects predominantly the antrum of the stomach then gastrin secretions are abnormally high especially with meal stimulated release of gastrin. These patients would tend to develop peptic ulcer disease.
Table 1.2   Gastritis.
Acute gastritis
Acute hemorrhagic and erosive gastropathy
Acute Helicobacter pylori gastritis
Chronic gastritis: Common forms
Helicobacter pylori gastritis
Chemical gastropathy
Aspirin and NSAIDs
Bile reflux
Atrophic gastritis
Chronic gastritis: Uncommon forms
Eosinophilic gastritis
Other infectious gastritis like Mycobacterium avium- intracellulare (MAI), tuberculosis (TB), viral, etc.
Crohn's disease—associated sarcoidosis Lymphocytic gastritis
Ménétrier's disease
Helicobacter pylori pathogenicity is decided by certain inherent virulence factors in the bacterium. Strains that produce a protein CagA associated with greater risk of developing gastric cancers and peptic ulcers.
Some patients develop a multifocal atrophic gastritis pattern where the infection of the corpus of the stomach eventually leads to a pattern of gastric atrophy with loss of gastric glands and eventually replacement of gastric glands by intestinal-type mucosa (intestinal metaplasia). This will eventually develop into dysplasia and gastric cancer. Because of gastric atrophy, the acid levels tend to fall and carcinogenic agents such as nitrosamine are not neutralized by acid.
The majority of patients with H. pylori-associated chronic gastritis, however, remain asymptomatic. Only a small number will develop duodenal ulcer disease and gastric cancer (Figs. 1.35 and 1.36).
zoom view
Fig. 1.35: Gastritis. Histologically, this is a severe gastritis.
zoom view
Fig. 1.36: Helicobacter pylori is easily identified on the biopsy of the stomach.
Other Infectious Gastritis
Granulomatous gastritis is a rare condition that may be caused by tuberculosis or Cryptococcus. Immunocompromised patients may occasionally acquire cytomegalovirus or mycobacterial infections involving Mycobacterium avium-intracellulare (MAI) species.
Gastritis Caused by Autoimmune Causes
Patients with autoimmune gastritis may have elevated antibodies such as an intrinsic factor and parietal cell antibodies. Two types of atrophic gastritis have been identified:
  1. In type A gastritis, the fundus is primarily affected resulting in reduced acid secretion. This causes the hyperplasia of gastrin-producing G cells and results in hypergastrinemia.
  2. In type B gastritis, the antrum is primarily affected and patients have normal serum gastrin.
Atrophic gastritis can be as a result of H. pylori infection when the H. pylori causes a pangastritis or a corpus gastritis. Thus, infection must be excluded by fecal antigen testing or any other readily available tests.
Atrophic gastritis may result in lower gastric acid production and may result in increased risk of gastric cancer. Atrophy of parietal cells also results in reduced production of B12 and development of B12 deficiency and pernicious anemia.
In terms of diagnosis, the endoscopic appearance of an atrophic stomach can be quite obvious with lack of rugal folds and biopsies would also be helpful in making the diagnosis.
Eosinophilic infiltration of gastric mucosa would result in eosinophilic gastritis. This condition is rare although it is increasingly being diagnosed. There may be a peripheral blood eosinophilia and they are sometimes associated with asthma and other allergic conditions. Patients may present with abdominal pain, fever, diarrhea or even ascites. Large antral folds may simulate other infiltrative processes like lymphoma and therefore biopsies are usually required to make a diagnosis. Patients may present with gastric outlet obstruction due to edema of the pylorus and infiltration of the antrum of the stomach (Fig. 1.37).
Biliary or Alkaline Reflux Gastritis (See Fig. 1.6)
Bile reflux causes a reddening appearance of the stomach on endoscopy. It is almost invariable as a consequence to partial gastrectomy and is termed biliary gastritis. It has a specific histological appearance characterized by foveolar hyperplasia.
Other Rare Gastritis
Hypertrophic gastritis or Ménétrier's disease is a very rare condition in which the fundic glands are replaced by a hypertrophic epithelium and forming massively enlarged mucosal folds. There is variable degree of inflammation.40
zoom view
Figs. 1.37A and B: Eosinophilic gastritis. CT image (A) shows thickened gastric antrum correlating with the endoscopic image (B) of the same patient.
Patients may present with pain, vomiting, bleeding or signs of hypoalbuminemia, which results from excessive protein loss as mucous is shed from the gastric mucosa. Other rare causes of gastritis include sarcoidosis, granulomatous gastritis and lymphocytic gastritis.
Acute Erosive Gastritis: Acute erosive gastritis may cause bleeding, requiring resuscitation and even emergency surgery. More usually, the bleeding can be controlled endoscopically and if nonsteroidal drugs are used, then they should be stopped and PPIs initially intravenously followed by oral PPI may be indicated. Very ill patients with septicemia shock, renal failure or hepatic failure may also develop acute ulcers, which may require PPI prophylactically.
Atrophic Gastritis: Atrophic gastritis may result in B12 deficiency so parenteral B12 replacement is required. If the atrophic gastritis is a result of H. pylori infection eradication of H. pylori would be wise.
Eosinophilic Gastritis: Eosinophilic gastritis usually responds very rapidly to corticosteroids, which may initially be necessary to give intravenously but that can easily be followed by a short course of oral prednisolone, usually starting with a dose of 30 mg and reducing over a week or so. Elimination of specific food allergies, use of leukotriene inhibitors montelukast or zafirlukast may also be helpful. Patients may have recurrence of this condition and may require a steroid sparing agent like azathioprine if they have repeated recurrence of this condition (See Figs. 1.20, 1.21 and 1.37).
Helicobacter-associated Gastritis: Treatment for Helicobacter-associated gastritis is H. pylori eradication, which has been discussed earlier. However, in asymptomatic individuals with H. pylori-associated gastritis, controversy exists as to whether they should have eradication or not. On balance with the 41hope of reducing the patients’ risk of developing gastric cancer, then H. pylori eradication is justified if found.
Biliary Reflux Gastritis: Biliary reflux gastritis responds well to bile chelating agents like cholestyramine. Aluminum hydroxide is also worth trying because it also has a bile acid–binding effect.
Carcinoma of the Stomach
Natural History
Symptoms and Signs: Gastric cancers are usually asymptomatic until invasion occurs through the submucosa and beyond. Hence, they often present late. The principal clinical features that they present with are weight loss, abdominal pain and vomiting. Weight loss is often the result of anorexia and pain on eating and early satiety (Table 1.3). Pain is often indistinguishable from those of peptic ulceration and may be relieved by PPIs and antacids or H2 antagonists. It usually takes the form of a vague upper abdominal discomfort often associated with a feeling of fullness. When the tumor is proximal to stomach there may be dysphagia as well. This may be from direct tumor obstruction or invasion of the nerve cells of the Auerbach plexus. The latter would cause pseudoachalasia syndrome with grossly dilated esophagus. Early satiety may be due to a diffuse form of gastric cancer (linitis plastica) where the stomach distends poorly because of the cancer. Distal tumors that block the pylorus or antrum will cause a gastric obstruction presenting with nausea and vomiting and sometimes hematemesis (Figs. 1.38 to 1.42).
A palpable mass may be found on examination. Signs of tumor spread may also be presenting features. Prominent left supraclavicular lymph node (Virchow's node) may be a sign of metastatic spread of gastric cancer and is also the most common sign of metastatic disease. When there are hepatic metastases then the liver may be often palpable and ascites may also be detected when there is peritoneal carcinomatosis.
Epidemiology: The incidence of gastric cancer in the United Kingdom and other developed countries is declining. Prevalence in the Far East and some Latin American countries remain very high. The increased risk in these areas is probably related to high rates of H. pylori infection. There is an encouraging decline in mortality from gastric cancer in the European centers (Fig. 1.43).
Table 1.3   Alarming symptoms.
Age >40
Rectal bleeding
Weight loss
Abdominal mass
zoom view
Fig. 1.38: Endoscopy showing a large gastric cancer.
zoom view
Fig. 1.39: Endoscopy: It appears unremarkable but the stomach was not distending with insufflation. This proved to be linitis plastica.
zoom view
Fig. 1.40: CT scan of the above showed linitis plastica: a thickened stomach infiltrated with malignant cells.
zoom view
Fig. 1.41: Gastric adenocarcinoma. Moderately well-differentiated carcinoma.
zoom view
Fig. 1.42: Gastric adenocarcinoma. Poorly differentiated carcinoma.
Management of Gastric Cancer
When gastric, etc. cancer is suspected a prompt endoscopy should be made. When cancer is found, multiple biopsies and brush cytology should be carried out and the patient then fully staged. The commonest staging system used is the TNM criteria. It is based on the tumor (T) nodal (N) metastases (M). This is being revised at present moment and the physician should consult the American Joint Committee on Cancer website for details.
The imaging modalities required to adequately stage patients include:
Abdominal and Pelvic CT Scan: CT scan of the abdomen and pelvis is very helpful in staging a disease. It will adequately pick up affected lymph nodes, liver metastases or ascites. However, lesions <5 mm may be missed by 44CT scanning. Patients with proximal gastric cancer should have a CT scan of the thorax as well (Fig. 1.44).
zoom view
Fig. 1.43: Stomach cancer: 1971–2014. European age-standardized mortality rates per 100,000 population, UK.Source:
zoom view
Fig. 1.44: Gastric cancer with liver metastasis.
Endoscopic Ultrasound: Endoscopic ultrasound (EUS) is helpful in gastric cancer staging. It is the most accurate method of staging the depth of tumor invasion. If the depth of invasion as evaluated at EUS shows that it is very superficial and not invaded submucosa then endoscopic resection may be possible. However, it is more useful as a tool for picking up tumors that have invaded the muscularis and also detects any local nodal involvement. In this situation patients may be offered neoadjuvant chemotherapy or chemoradiotherapy prior to surgery.45
Positron-emission Tomography Scan: Positron-emission tomography (PET) using a radio labeled (positron emitting) isotope of glucose (FDG). The FDG is taken up by tumor cells and is therefore valuable in detecting any distant metastases. However, patients with peritoneal carcinomatosis may be missed on PET scanning.
Staging Laparoscopy: If there is any doubt as to whether the tumor is operable or not then a staging laparoscopy is usually recommended. This is especially true if CT or EUS show more advanced tumors, particularly stage T3/T4 tumors but no metastases. Laparoscopy may be needed to establish operability.
Treatment of Gastric Cancer
If it is possible, surgical resection of the tumor is still the primary treatment. However, the treatment of gastric cancer is based on the staging of the tumor. A combination of neoadjuvant chemotherapy; adjuvant chemotherapy and chemotherapy and surgery is available to the patient.
Neoadjuvant chemotherapy refers to chemotherapy given before surgery to downstage the tumor. This is given in patients with bowel T3 or T4 tumors or patients with perigastric nodes.
Adjuvant chemotherapy refers to chemotherapy given along with surgery. The aim of adjuvant chemotherapy is to improve survival by eliminating any residual tumor after surgery.
The exact treatment protocol for each individual patient is usually discussed at the multidisciplinary team meeting where the imaging, histology and overall patient fitness are discussed. If the patient is fit for surgery, then every attempt is made to improve surgical outcome. Best treatments are still a subject for research and patients should be considered for entering many of the clinical trials that are currently running.
Prognosis and Screening
Successful surgical resection of an early gastric cancer carries a 90% 5-year survival rate. Invasive gastric cancers, however, have a very poor prognosis. In countries where there is high incidence of gastric cancer such as Japan, screening may be a viable option and pick up cases of early gastric cancer. This remains the best way of improving outlook of the disease. However, in countries where gastric cancer incidence is low risk, like in the United Kingdom, screening is not viable or a cost-effective option.
Gastric Lymphomas (Figs. 1.45 to 1.50)
Gastric lymphomas account for about 5% of gastric malignancies and for about 60% of all GI lymphomas. Symptoms and endoscopic features may be indistinguishable from those of gastric cancers. The endoscopic appearance may be that of a polypoidal lesion, ulcerating lesion or an infiltrating lesion.46
zoom view
Fig. 1.45: Gastric lymphoma. On endoscopy, the appearances can vary from discrete ulcers to diffuse infiltrative picture.
zoom view
Fig. 1.46: Gastric lymphoma. Appearance after chemotherapy shows scarring.
zoom view
Fig. 1.47: Gastric lymphoma. Sampling of the deeper tissue may be necessary to make a diagnosis. Here a fine needle aspirate was taken using endoscopic ultrasound.
zoom view
Fig. 1.48: Gastric lymphoma. Grossly thickened stomach is clearly demonstrated.
zoom view
Fig. 1.49: Gastric lymphoma. Proliferation of infiltrative lymphoma cells.
However, clues that the lesion is a lymphoma rather than gastric carcinoma may be the younger age group or patients who had previous organ transplantation receiving immune suppressive therapy. Almost all the gastric cancers are the B-cell variety and are divided into two types: (1) those with mucosa-associated lymphoid tissue (MALT lymphomas) that account for about half of the gastric lymphomas encountered, and (2) those with diffuse, large B-cell lymphoma that account for the other half. MALT lymphomas (also referred to as extranodal marginal zone B-cell lymphoma) is often associated with H. pylori infection. Eradication of H. pylori infection may result in involution of these tumors.
Proper staging evaluation includes CT scanning and PET scanning. Discussions at the multidisciplinary meeting as to best management will 48depend upon tissue type, grade of malignancy and extent of disease. A combination of H. pylori eradication if indicated, radiotherapy, chemotherapy and immunotherapy is available depending upon the specific stage and type of lymphoma. Prognosis is usually good.
zoom view
Fig. 1.50: Gastric lymphoma. Immunohistochemical staining helps identify the cell type. The vast majority are B-cell lymphomas and about 40% are mucosa-associated lymphoid tissue (MALT) lymphomas which are associated with H. pylori infection.
Gastric Polyps
Natural History
Gastric polyps are frequently encountered on endoscopy. The commonest type of polyps found is fundic gland polyps (Fig. 1.51) (also known as cystic fundic polyps). They account for over 90% of gastric polyps. They pose no significant overall risk to the patient. They have no malignant potential. These polyps as their name implies are found mainly in the fundus of the stomach although they do occur in the body of stomach and occasionally in antrum as well. They are cystic in nature. They are also commonly seen in patients who have been on long-term PPIs. Patients with familial adenomatous polyposis (FAP) may also have proliferation of these fundic gland polyps and if there is a family history then investigation of colon would be advised.
True adenomas of the stomach are relatively rare, occurring in about 5% of gastric polyps. They have a similar premalignant potential as colonic adenomas. Hence, they are best removed endoscopically if possible. It may be difficult endoscopically to decide the nature of the polyps then biopsies are best performed to establish diagnosis.
Other polyps that may be encountered in the stomach include hamartomatous polyps found in polyposis syndromes such as Peutz–Jeghers. Also, quite rare are gastric carcinoids. Four types of gastric carcinoids have been identified.49
zoom view
Figs. 1.51A to C: Fundic gland polyps are a common finding on endoscopy and are usually associated with acid suppression (PPI use). It may rarely be associated with polyposis syndromes.
The most common is Type I which is well differentiated and associated with atrophic gastritis usually in the elderly and of relatively good prognosis, whereas Type II is multifocal and associated with multiple endocrine neoplasia and Zollinger–Ellison syndrome. Type III is solitary, well differentiated but in the absence of gastric atrophy and Type IV is the poorly 50differentiated variety. Types III and IV are more aggressive and would require resection.
zoom view
Fig. 1.52: Gastrointestinal stromal tumor (GIST) lesion. A polypoid lesion sometimes with an umbilicated center. This proved to be a GIST.
Other lesions that look like polyps include gastrointestinal stromal tumors (GIST) (Fig. 1.52). These may be asymptomatic and may look like an elevated umbilical lesion in the stomach and are usually solitary. Occasionally, they might cause complications like bleeding and may undergo malignant transformation. In general, if they are <2 cm surveillance is probably not necessary. If they are >2 cm then it is worth considering EUS followed by surgery if it is judged to have malignant features. If in doubt, surgical excision should be considered.
Natural History
Cross-sectional studies have shown that in European studies more than 75% of patients with gallstones are asymptomatic. In a large cohort study with a median follow-up of over 17 years, <20% of patients with asymptomatic gallstones develop symptoms. Also in their follow up, their initial symptoms are typically not severe. It is therefore widely accepted that cholecystectomy for patients with asymptomatic gallstones is not advised. However, of the patients who do develop symptoms, a significant number develop complications. Once symptoms develop, probably about one-third will continue to have symptoms in the subsequent 2 years. Finally of the patients who do have symptoms, up to 10% develop serious complications after a median follow-up of 10 years. These complications include, acute cholecystitis, choledocholithiasis with or without acute cholangitis and gallstone pancreatitis. Hence, patients with symptomatic gallstones should be offered therapy.51
About 8% of white populations in the United Kingdom have gallstones and the incidence is increasing. The prevalence increases with age and 80% are female. The incident varies considerably with population groups. Western Caucasian, Hispanic and Native American populations have the highest incidence whereas African, Eastern European and Japanese populations have a relatively low incidence. Large ultrasound-based studies in Europe suggest that in individuals between the ages of 30 and 70 years, 18% of women and 9% of men have gallstones.
Etiology and Pathogenesis
The majority of gallstones found among European Caucasian populations are cholesterol-based gallstones. Here, there are several risk factors that increase the tendency to produce gallstones. Obviously, the older the patient, the more time they have to produce gallstones. Women are twice as likely to produce stones as men presumably due to the presence of sex hormones. Pregnancy itself is a major risk factor. This may be caused by estrogen stimulating increasing cholesterol secretion in the bile. Similarly, oral contraceptives may affect gallstone production presumably by the same mechanism.
Family history and genetics play an important part as does obesity itself. Curiously, rapid weight loss is a risk factor of gallstone formation and one of the complications of bariatric surgical operations. Other risk factors include diabetes, liver disease and Crohn's disease. Pigment stones are more likely in patients with hemolytic anemia from any cause. Drugs such as octreotide are also known to promote formation of gallstones. This may be due to its effects on gallbladder motility and increasing the chance of gallbladder stasis. Gallstone formation may be also a complication of total parenteral nutrition. This is probably due to its effects of causing biliary stasis. Surgical removal of terminal ileum will also affect enterohepatic circulation of bile acids and promote the formation of gallstones.
In the absence of any symptoms, there is no justification in carrying out any specific treatment of gallstones. Furthermore, many patients have nonspecific abdominal symptoms and the finding of gallstones by ultrasound may be quite incidental. It is therefore important to ascertain that the symptoms are directly caused by the presence of gallstones. This may be very difficult and ultimately is a clinical decision.
The mainstay of treatment is laparoscopic cholecystectomy. In expert hands, conversion rate to open cholecystectomy is usually <2% and duct injuries <0.1%. The main complications are bile leak, hemorrhage and retained stones.
For patients with previous cholecystitis, cholangitis or pancreatitis, risk of recurrence is high and therefore cholecystectomy is recommended. 52If the LFTs are abnormal or there is dilatation of the common bile duct on ultrasound, then an MRCP is recommended before embarking on surgery to ensure that there are no stones in the common bile duct (Fig. 1.9). Stones in the common bile duct can be removed by ERCP and that should be performed prior to surgery (Fig. 1.10).
Medical Management of Gallstones: The medical management of gallstones have proved very disappointing. The mainstay of treatment uses hydrophilic bile acids such as chenodeoxycholic acid or ursodeoxycholic acid. For dissolution to be successful, the stones must be predominantly of cholesterol origin and not to be calcified. CT scanning is a good method to see if there is significant calcification of the stones. The stones must also be of small size, preferably <10 mm and the gallbladder must be functioning adequately. Even with all the above criteria met, the drug has to be given for a minimum of a year to achieve adequate dissolution. Hence, it is only in very exceptional circumstances that medical therapy for gallstones is appropriate.
Management of Polypoidal Lesions in the Gallbladder: Polypoidal lesions of the gallbladder are frequently found on ultrasound. The commonest polypoidal lesion is adenomyomatosis. This is characterized by mucosal thickening and localized muscle wall thickening and sometimes with a prominent diverticula formation. It is thought to be predominantly asymptomatic. If the patient exhibits symptoms that sound biliary, then it may be worth considering cholecystectomy in limited cases. The association between adenomyomatosis and gallbladder cancer is a controversial one and there is no direct evidence to suggest that the two are causally linked.
Chronic Mesenteric Ischemia
Natural History, Symptoms and Signs
Clinically, significant obstruction of one of the main mesenteric vessels (celiac axis of the superior/inferior mesenteric arteries) usually present with acute infarction of the bowel. However, intermittent bowel ischemia resulting in abdominal angina can occasionally occur. Typically, the patient experiences a pain in the central abdomen usually 15–30 minutes after meals and it may last for several hours. This pain results in fear of eating and with bowel ischemia there is also poor absorption of nutrients and the two factors result in marked weight loss. Typically patients are elderly, have evidence of atheromatous disease elsewhere like cardiac disease and peripheral vascular disease and smoking is a major risk factor.
Computed tomography scanning is helpful in its diagnosis in identifying stenosis of the mesenteric vessels. The presence of high-grade vascular stenosis in at least two of the major vessels (celiac, superior/inferior mesenteric) are clues that the symptoms are due to mesenteric ischemia. MR angiography is also a valuable modality.53
zoom view
Fig. 1.53: Duodenal tumor obstructing the gastric outlet.
zoom view
Fig. 1.54: Obstruction in duodenum can be stented.
True intestinal ischemia carries a poor prognosis. Some form of revascularization would be necessary. The treatment of choice is angioplasty and stenting carried out by interventional radiologists. Open surgery may be required if endovascular treatment is not successful.
Miscellaneous Conditions: True duodenal cancers are rare and may be associated with familial adenomatous polyposis syndromes (FAP) (see Chapter 5) (Figs. 1.53 and 1.54).
  1. Irritable Bowel Syndrome
  1. Collins S. A role for the gut microbiota in IBS. Nat Rev Gastroenterol Hepatol. 2014;11(8):497–505.
  1. Ford AC, Talley NJ, Spiegel BM, et al. Effect of fibre, antispasmodics, and peppermint oil in the treatment of irritable bowel syndrome: systematic review and meta-analysis. BMJ. 2008;337:a2313.

  1. 54 Ford AC, Quigley EM, Lacy BE, et al. Effect of antidepressants and psychological therapies, including hypnotherapy, in irritable bowel syndrome: systematic review and meta-analysis. Am J Gastroenterol. 2014;109(9):1350–65.
  1. Talley NJ. Irritable bowel syndrome. Intern Med J. 2006;36(11):724–8.
  1. Wedlake L, A'Hern R, Russell D, et al. Systematic review: the prevalence of idiopathic bile acid malabsorption as diagnosed by SeHCAT scanning in patients with diarrhoea-predominant irritable bowel syndrome. Aliment Pharmacol Ther. 2009;30(7):707–17.
  1. Helicobacter pylori and Peptic Ulcer Disease
  1. Lanas A, Chan FK. Peptic ulcer disease. Lancet. 2017;390(10094):613–24.
  1. Malfertheiner P, Megraud F, O'Morain CA, et al. European Helicobacter Study Group. Management of Helicobacter pylori infection—the Maastricht IV/Florence Consensus Report. Gut. 2012;61(5): 646–64.
  1. Tsai HH. Helicobacter pylori for the general physician. J R Coll Physicians Lond. 1997;31(5):478–82.
  1. Functional Dyspepsia
  1. Brun R, Kuo B. Functional dyspepsia. Ther Adv Gastroenterol. 2010;3(3):145–64.
  1. Gastric Cancer
  1. Fuchs CS, Mayer RJ. Gastric carcinoma. N Engl J Med. 1995;333(1):32–41.
  1. Macdonald JS, Smalley SR, Benedetti J, et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 2001;345(10):725–30.
  1. Neugut AI, Hayek M, Howe G. Epidemiology of gastric cancer. Semin Oncol. 1996;23(3):281–91.
  1. Gallstones
  1. Heuman DM. Gallstones (Cholelithiasis) Clinical Presentation: History, Physical Examination.
  1. Portincasa P, Moschetta A, Palasciano G. Cholesterol gallstone disease. Lancet. 2006 368(9531):230–9.