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CHAPTER 5 | PANCREATICDISORDERS
for diagnosis. However, very low FE values are most probably associated with PEI, whereas high
values (>500 microg/ g) allow its exclusion. The coecient of fat absorption is the accepted, but
rarely used, gold standard for the diagnosis of steatorrhoea. It involves measuring total faeces over
three days while consuming a fat- controlled diet. Alternative indirect tests include a 3C- labelled
mixed triglyceride breath test and estimation of pancreatic secretion volume with secretin- MRCP.
Both are limited by sensitivity and availability for use in routine clinical practice. Direct tests involve
the collection of duodenal juices in response to a hormonal stimulus (secretin or CCK) and are the
accepted reference standard allowing the quantication of pancreatic exocrine secretion.
Löhr JM, Dominguez- Munoz E, Rosendahl J etal. United European gastroenterology evidencebased guidelines for the diagnosis and therapy of chronic pancreatitis (HaPanEU). United European
Gastroenterol J. 207 Mar;5(2):53– 99. Doi:0.77/ 205064066684695.
13. A. Less than 10% of patients who achieve pain relief with EUS- guided coeliac
plexus block will have ongoing pain relief after two years
• Pain is the predominant symptom in CP, occurring in 94% of cases
• Management includes alcohol cessation, oral analgesia, and targeted endoscopic/ surgical
therapy for structural lesions (e.g. pseudocysts, ductal calculi)
• The pain relief of EUS- guided coeliac plexus block is often short- lived
Pain is the rst presentation of CP in most patients and is usually the most disabling symptom of the
condition. Only about 6% of patients with CP report being pain free. There is no good evidence to
suggest that ongoing inammation and parenchymal destruction will ultimately lead to reduction in
pain over time. The mechanisms underlying pain in CP are complex and include structural pathology
(e.g. pseudocysts, common bile duct, and duodenal obstruction) and ductal lesions (e.g. strictures,
calculi) that may respond to targeted radiological or endoscopic therapy. However, a large group
of patients will have neurogenic pain when no clear alternative source of pain can be identied. In
these cases, cessation of alcohol, and possibly smoking, can improve pain. Pharmacological analgesia
should follow the principles of the ‘pain relief ladder’ provided by the World Health Organization.
Many patients will require opiates, in which case tramadol is preferred over morphine because of
its association with fewer gastrointestinal side eects for the same degree of analgesia. Adjuvant
analgesics may include antidepressants, anticonvulsants (e.g. gabapentin), and anxiolytics. EUSguided coeliac plexus blocks can improve pain in half of patients, but the eect is often short with
<0% experiencing pain relief for >24 weeks.
Löhr JM, Dominguez- Munoz E, Rosendahl J etal. United European gastroenterology evidencebased guidelines for the diagnosis and therapy of chronic pancreatitis (HaPanEU). United European
Gastroenterol J. 207 Mar;5(2):53– 99. Doi:0.77/ 205064066684695.
14. B. Prednisolone
• Autoimmune pancreatitis type (AIP) is the pancreatic manifestation of IgG4- related
disease (IgG4- RD), and often presents with a pancreatic mass and jaundice mimicking
pancreatic cancer
• Associated features include multi- organ involvement, history of atopy, and elevated serum
IgG4 and IgE
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AIP is the pancreatic manifestation of IgG4- RD:an immune- mediated condition associated with
bro- inammatory mass- forming lesions that can occur at nearly any anatomic site. It often presents
as a multi- organ disease, and may be confused with malignancy, infection, or other inammatory
conditions. There is a male preponderance and often a clinical history of atopy. Serum IgG4 levels
are raised in most (65%– 80%) patients. However, they are non- specic and can be elevated in
other malignant and inammatory conditions, and 5% of healthy individuals. While the classical
imaging description of AIP is with a diuse sausage- shaped pancreas, half of patients have a
discrete pancreatic head mass mimicking cancer. Localized lymphadenopathy is common and does
not distinguish it from malignancy. Evidence of extra- pancreatic organ involvement supports the
diagnosis. IgG4- RD is corticosteroid- responsive and prednisolone therapy would be the optimal
rst- line therapy. Biliary stenting has a role if there is evidence of biliary sepsis or corticosteroid
treatment will be delayed because of a suspicion of malignancy. Rituximab is currently reserved as
third- line therapy for patients who have relapsed or developed side eects on steroids, usually after
a trial of an immunomodulator (e.g. Azathioprine).
Culver EL, Chapman RW. IgG4- related hepatobiliary disease:an overview. Nat Rev Gastroenterol
Hepatol. 206 Oct;3(0):60– 62. Doi:0.038/ nrgastro.206.
15. C. Pancreatoduodenectomy is often required
• Para- duodenal ‘groove’ pancreatitis occurs in the tissue between the duodenal wall and the
pancreatic head
• It can be dierentiated from peri- pancreatic cancer and autoimmune pancreatitis by classical
histopathology and imaging characteristics
• Pancreatoduodenectomy leads to complete pain relief in 75% of patients
Para- duodenal pancreatitis (groove pancreatitis) is an uncommon segmental CP aecting the
‘groove’ area between the pancreatic head, duodenum, and common bile duct. It often surrounds
the minor ampulla and accessory duct. It predominantly aects males aged 40– 50years with a
history of alcohol abuse, and can cause severe intermittent upper abdominal pain, nausea, and
vomiting (due to disordered gastric emptying and duodenal stenosis). Weight loss can be severe,
mimicking pancreatic cancer.
Serum pancreatic and hepatic enzymes are often slightly elevated whereas serum carbohydrate
antigen (CA 9- 9) and IgG4 levels are usually normal. The duodenum is usually oedematous,
nodular, or cobblestone in appearance with stenosis on endoscopic evaluation. Histology from
duodenal biopsies show duodenal wall cysts, Brunner gland hyperplasia, dilation of Santorini’s duct,
and protein plaques in the pancreatic duct. Imaging with EUS, CT, or magnetic resonance (MR) may
demonstrate focal thickening and abnormal enhancement of the second portion of the duodenum,
and cystic change in the duodenal wall.
Conservative treatment options include analgesia and smoking/ alcohol cessation. Endoscopic
stenting of the minor papilla has been reported, but long- term outcomes remain unclear.
Pancreatoduodenectomy is the treatment of choice when the condition remains dicult to
distinguish from pancreatic carcinoma or with persisting symptoms when resection leads to
complete pain relief in >75%.
Jani B, Rzouq F, Saligram S etal. Groove pancreatitis:a rare form of chronic pancreatitis. N Am J Med
Sci. 205 Nov;7():529– 532. Doi:0.403/ 947- 274.70624.
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16. A. EUS
• In potentially resectable pancreatic tumours, EUS is required prior to surgery to help identify
lymph node involvement and vascular invasion
• Pre- operative biliary drainage in patients with biliary obstruction, without cholangitis
secondary to resectable pancreatic tumours, is associated with a higher rate of post- operative
complications
This patient has a potentially resectable pancreatic mass with mild biliary obstruction but no
evidence of cholangitis or metastatic disease on cross- sectional imaging. In this setting, the
European Society for Medical Oncology recommend further assessment with EUS, which is
now widely used in the staging of pancreatic cancer prior to surgery. EUS can detect metastatic
lymph nodes and vascular invasion not seen on imaging, and helps to predict overall resectability.
It can also acquire tissue via ne needle aspiration, which can conrm the primary diagnosis and
help stage disease by sampling atypical portocaval lymph nodes or incidental hepatic metastases.
Percutaneous biopsy of a liver metastasis can be used in metastatic disease, but percutaneous
biopsy of the pancreas is contra- indicated in potentially resectable cases because of the risk of
peritoneal seeding. In uncomplicated biliary obstruction secondary to resectable pancreatic cancer,
as in this case, pre- operative drainage should be avoided because it is associated with higher rates
of post- operative complications. In cases of cholangitis where biliary decompression is necessary,
further studies are needed to determine the best treatment modality (e.g. ERCP vs percutaneous
transhepatic cholangiogram; plastic vs metal stenting). Staging laparoscopy in addition to imaging
and EUS has been suggested by some groups in order to exclude peritoneal metastases but it is not
widely practised.
Ducreux M, Cuhna AS, Caramella C etal. Cancer of the pancreas:ESMO clinical practical guidelines.
Ann Oncol. 205 Sep;(26 Suppl 5):v56– 68. Doi:0.093/ annonc/ mdv295.
17. E. Level positively correlates with serum bilirubin
• CA 9- 9 does not have the necessary sensitivity or specicity to facilitate its use in the
diagnosis of pancreatic adenocarcinoma
• Cholestasis from any cause can cause an elevation in CA 9- 9
The carbohydrate antigen sialyl Lewis Ais more commonly referred to as ‘CA 9- 9’, the name of
the monoclonal antibody currently used for its detection. Elevated CA 9- 9 is best studied in the
context of pancreatic adenocarcinoma being elevated in >80% patients with advanced disease.
However, it can also be elevated in a range of other benign and malignant conditions, and therefore
does not carry the necessary sensitivity or specicity to be utilized in the diagnosis of pancreatic
cancer. CA 9- 9 is related to the Lewis blood group antigens and only patients belonging to the
Le (α- β+) or Le (α+β- ) blood groups will express the CA 9- 9 antigen. Approximately 6% of
the caucasian population and 22% of the black population are Le(α- β- ) and do not generate the
specic sialyl antigen. Conversely, CA 9- 9 strongly correlates with the level of bilirubin and can be
elevated with any cause of cholestasis. CA 9- 9 does have signicant prognostic value and a failure
of CA 9- 9 level to normalize after pancreatic cancer resection is associated with a poor prognosis
and suggests residual disease. CA 9- 9 can also be used as a surrogate marker of response to
chemotherapy with a ≥20%– 50% decrease in CA 9- 9 associated with a positive tumour response
and increased survival. Apre- operative serum CA 9- 9 level ≥500 U/ ml predicts worse prognosis
after surgery.
Ducreux M, Cuhna AS, Caramella C etal. Cancer of the pancreas:ESMO clinical practical guidelines.
Ann Oncol. 205 Sep;26 (Suppl 5):v56– 68. Doi:0.093/ annonc/ mdv295.
CHAPTER 5 | ANSWERS
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18. C. Multiple endocrine neoplasm type 1
• Multiple endocrine neoplasia type is the main inherited cause of p- NETs
• Other rare inherited causes are Von Hippel– Lindau disease, neurobromatosis type (von
Recklinghausen’s syndrome) and tuberous sclerosis
P- NETs are a heterogeneous group of tumours derived from the endocrine pancreatic cells (e.g.
α- , β- , δ- , and γ- cells) and represent just <2% of all pancreatic neoplasms. They express at least
two of the following markers:chromogranin A, synaptophysin and/ or neuron- specic enolase,
and can secrete a variety of neuropeptides leading to a range of clinical symptoms (e.g. carcinoid
syndrome). Most p- NETs occur as sporadic tumours although a proportion occur as part of an
inherited syndrome. Multiple endocrine neoplasia type remains the most important inherited
condition, responsible for 20%– 30% of gastrinomas and 5% of insulinomas. Other inherited
conditions predisposing to p- NETS are Von Hippel– Lindau disease, neurobromatosis type (von
Recklinghausen’s syndrome), and tuberous sclerosis.
Falconi M, Eriksson B, Kaltsas G, etal. Consensus guidelines update for the management of functional
p- NETs (F- p- NETs) and non- functional p- NETs (NF- p- NETs). Neuroendocrinology. 206;03(2):53–
7. Doi:0.59/ 0004437.
19. E. Serous cystadenoma
• Secondary cystic changes can occur in frankly malignant pancreatic adenocarcinomas
• Cystic lesions with malignant potential include IPMNs, mucinous cystic neoplasms, and solid
pseudopapillary neoplasms
• Serous cystadenomas and simple cysts are benign
Three to fourteen per cent of patients undergoing routine imaging are now incidentally found to
have pancreatic cysts. Multiple types are recognized with varying natural histories and malignant
potential. The most aggressive cystic lesions are typically cystic changes in frankly malignant,
otherwise solid lesions, such as ductal adenocarcinoma or neuroendocrine tumours. Lesions
with malignant potential include IPMN and mucinous cystic neoplasm. Solid pseudopapillary
neoplasm has a known, but low, risk for malignancy. The other end of the spectrum comprises
benign neoplasms (such as serous cystadenoma) and non- neoplastic lesions (such as simple cysts,
lymphoepithelial cysts). Serous cystadenomas can be macrocystic, which appear similar to mucinous
lesions on imaging, or microcystic, which have a typical honeycomb appearance and central scar.
Stark A, Donahue TR, Reber HA etal. Pancreatic cyst disease:a review. JAMA. 206 May
3;35(7):882– 893. Doi:0.00/ jama.206.4690.
20. B. Surgical resection
• Absolute indications for surgical resection of IPMN include jaundice, pancreatic duct dilatation
>0mm, and solid mass
• Patients not meeting criteria for surgery should have six- month follow- up in the rst year, and
then yearly follow- up with MRI or EUS
IPMN can be classied according to their association with the pancreatic ducts. Main- duct IPMNs
are characterized by dilation of the main pancreatic duct (MPD) of >5mm, for which other causes
of ductal obstruction have been ruled out, are mostly located in the pancreatic head and carry the
highest risk of malignancy. Branch duct IPMNs are grape- like cysts (>5mm) that communicate with
the main duct. They have a preference for the uncinate process, can be multifocal, and have lower
risk of malignancy. Absolute indications for surgical resection in patients with suspected IPMN
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include jaundice, an enhancing mural nodule ≥5mm, a solid mass, a positive malignant cytology, or a
dilated MPD diameter measuring ≥0mm. Patients outside these criteria require six- month followup in the rst year, and then yearly follow- up with MRI/ EUS if no indications for surgery arise.
European evidence- based guidelines on pancreatic cystic neoplasms. The European Study Group on Cystic
Tumours of the Pancreas. Gut. 208 May;67(5):789– 804. Doi:0.36/ gutjnl- 208- 36027.
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chapter
SMALL INTESTINALDISORDERS
1. A 32- year- old man was reviewed in the emergency department with
6
QUESTIONS
diarrhoea secondary to enteropathogenic Escherichia coli infection. Oral
rehydration therapy (ORT) was suggested to improve hydration status.
Through which ion transporter does ORT act?
A. Cystic brosis transmembrane conductance regulator (CFTR)
B. Epithelial sodium channel (ENaC)
C. Glucose transporter 1 (GLUT1)
D. Sodium/ glucose cotransporter 1 (SGLT1)
E. Sodium/ potassium/ chloride cotransporter 1 (NKCC1)
2. A 46- year- old woman presented with a 5- month history of profuse
diarrhoea despite fasting, and associated abdominal bloating. She
complained of increasing fatigue and ushing, and appeared dehydrated.
Investigations:
Haemoglobin 125 g/ L
Serum sodium 144mmol/ L
Serum potassium 1.9mmol/ L
Serum urea 7.3mmol/ L
Serum creatinine 136 µmol/ L
Plasma viscosity 1.76 mPa/ s
Which of the following is the most likely diagnosis?
A. Bile acid diarrhoea
B. Carcinoid syndrome
C. Coeliac disease
D. Vasoactive intestinal polypeptide (VIP)oma
E. Vibrio cholera infection
Best of Five MCQs for the European Specialty Examination in Gastroenterology and Hepatology. Thomas Marjot, Colleen G C McGregor,
Tim Ambrose, Aminda N De Silva, Jeremy Cobbold, and Simon Travis, Oxford University Press (2021). © Oxford University Press.
DOI: 10.1093/oso/9780198834373.003.0006
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CHAPTER 6 | SMALL INTESTINALDISORDERS
3. A 37- year- old with diarrhoea was reviewed in outpatients and was
interested to understand more about gut hormones.
Regarding gut hormones, which of the following statements is true?
A. Cholecystokinin is produced by Icells of the small intestine in response to ingested
carbohydrate
B. Gastrin is produced by G cells of the duodenum in response to raised gastric pH
C. Glucagon- like peptide 1 stimulates glucose- dependent glucagon release from the
pancreatic islets
D. Glucagon- like peptide 2 (GLP- 2) inhibits gastric emptying and gastric acid production,
induces small bowel mucosal growth, and stimulates mesenteric blood ow
E. Somatostatin increases gut motility and stimulates pancreatico- biliary secretions
4. You reviewed a 47- year- old patient in clinic with a body mass index
(BMI) of 34kg/ m2. They asked for your opinion on the role of leptin in
obesity.
Which of these statements is true?
A. Ethnicity exerts a signicant eect on leptin concentrations
B. Leptin is a product of the lep gene primarily expressed in adipocytes
C. Most patients with obesity have low serum leptin
D. Overeating reduces circulating leptin levels
E. Supraphysiological doses of leptin may reduce food intake in patients of normal weight
5. A 43- year- old woman with a BMI of 37kg/ m2 was referred for gastric
bypass surgery. She was consented for a research study investigating
satiety hormones in those undergoing bariatric surgery.
Which of the following statements best describes the behaviour of
ghrelin?
A. Levels fall before meal ingestion but gradually rise in the subsequent two hours
B. Levels remain unchanged before and after meal ingestion
C. Levels rise sharply before and fall shortly after meal ingestion
D. Levels rise sharply before meal ingestion and remain high afterwards for several hours
E. Levels are unchanged before meal ingestion but fall rapidly afterwards
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6. A 47- year- old man presented with intermittent, watery diarrhoea. He
had a 25- year history of type Idiabetes with retinopathy and peripheral
neuropathy requiring an insulin pump. Investigations were unremarkable
and autonomic enteropathy was suspected.
Which of the following neurotransmitters is most responsible for
activating sensory neurones following stimulation of stretch receptors in
the bowel?
A. Acetylcholine
B. Nitric oxide
C. Serotonin
D. Substance P
E. Vasoactive intestinal peptide (VIP)
7. A 25- year- old scientist was referred for a second opinion due to
persistent abdominal pain, nausea, abdominal distension, and weight
loss. All investigations had been normal and enteric dysmotility was
suspected. She enquired about measuring small bowel contractility.
Which of the following would you recommend as best for measuring
small intestinal contractile patterns?
A. Barium follow through
B. Catheter- based manometry
C. Lactulose hydrogen breath test
D. Scintigraphy
E. Wireless motility capsule
8. A 38- year- old man presented with recurrent abdominal pain, every
other day, for the previous three months.
Which of the following most favours a diagnosis of irritable bowel
syndrome (IBS)?
A. Bloating
B. Early satiety
C. Mucus discharge per rectum
D. Nausea
E. Worsening pain with defecation
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CHAPTER 6 | SMALL INTESTINALDISORDERS
9. A 37- year- old woman with a history of functional abdominal pain was
referred for a second opinion and was keen to know about options for
managing her ongoing pain. She had had no response to antispasmodics,
amitriptyline, duloxetine, or hypnotherapy.
Which of the following should you recommend next?
A. Fentanyl patch
B. Gabapentin
C. Oxycodone immediate release
D. Sacral nerve stimulator
E. Sertraline
10. You have been invited to present to the local coeliac disease patient
support group about the practicalities of a gluten- free diet.
Which one of the following foods and drinks could be included in a
gluten- free diet?
A. Barley squash
B. Champagne
C. Couscous
D. Porridge oats
E. Scotch eggs
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11. A 29- year- old white British nursery worker attended clinic with a twoyear history of abdominal bloating, discomfort, and an alternating bowel
habit. She had not lost weight, had no rectal bleeding or skin rashes, but
was frequently tired. She had a sister with type 1 diabetes.
Investigations:
Haemoglobin 121 g/ L
White cell count 5.4 × 109/ L
Platelet count 174 × 109/ L
Mean corpuscular volume (MCV) 87 fL
Serum ferritin 12 μg/ L
Serum C- reactive protein (CRP) 0.2 mg/ L
Serum vitamin B12 358 ng/ L
Serum folate 1.9 μg/ L
Serum vitamin D 51nmol/ L
immunoglobin Atissue transglutaminase
antibody (IgA TTG)
Total IgA 0.05 g/ L
human leukocyte antigen (HLA) status DQ 2.5 heterozygote
Gastroscopy Macroscopically normal
Duodenal histology Marsh 3C villous atrophy and crypt
What is the most appropriate test to establish a diagnosis?
A. Faecal calprotectin
B. Helicobacter pylori serology
C. HIV serology
D. Periodic- acid Schi (PAS) staining of duodenal biopsies
E. Serum IgG TTG antibody
<0.2 U/ ml
hyperplasia with intraepithelial
lymphocytosis
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