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- •Series Editors’ preface
- •Editors’ preface
- •Evidence-based practice in surgery
- •Contributors
- •Liver function and failure
- •Hepatic, biliary and pancreatic anatomy
- •Staging and assessment of hepatobiliary malignancies
- •Benign liver lesions
- •Primary malignant tumours of the liver
- •Colorectal liver metastases
- •Non-colorectal hepatic metastases
- •Portal hypertension and liver transplantation
- •Pancreas and islet transplantation
- •The spleen and adrenal glands
- •Gallstones
- •Benign biliary tract diseases
- •Malignant lesions of the biliary tract
- •Complicated acute pancreatitis
- •Chronic pancreatitis
- •Pancreatic adenocarcinoma
- •Cystic and neuroendocrine tumours of the pancreas
- •Hepatobiliary and pancreatic trauma

Chapter 17
pancreatic remnant. Given the dismal survival for
those with invasive disease and lack of subsequent
curative therapies, it is questionable whether this
type of follow-up should be limited to those with
dysplasia or PANIN at the margin, or for patients
with invasive disease >
3 years from resection when
the conditional survival is more favourable. In
contrast, for those without high-grade dysplasia or
malignancy at the margin, the AGA guidelines do
not recommend ongoing surveillance (excluding
mixed-type IPMN or family history of pancreatic
cancer), again based on weak supporting evidence.
There is a lack of reliable evidence regarding
recommended follow-up regimens. Both the IAP and
AGA guidelines acknowledge this, but feel it is
reasonable to perform cross-sectional imaging at a
variable frequency (1–2yearly).
tumour markers is currently not supported.
2,23
The routine use of
23
Given that recurrence would seem to occur most
commonly within the pancreatic remnant, Tomimaru
et al. have proposed performing a pancreaticogastrostomy to allow easy endoscopic follow-up of
the duct.
38
Additionally, the association of IPMNs
with other gastrointestinal malignancies should
alert physicians to investigate new gastrointestinal
symptoms promptly.
Pancreatic neuroendocrine
tumours
Pancreatic neuroendocrine tumours (PNETs) are rare
tumours with a reported incidence of 0.2–0.4 per
100 000, although post-mortem studies have reported
PNETs in up to 10% of the population.39 Eighty-five
per cent of PNETs are non-syndromic (non-functional),
with the rest comprised of syndromic tumours
which carcinoid, insulinoma and gastrinoma are the
most common.
41
The aetiology is poorly understood
and although the majority of tumours are sporadic,
there are associations with several hereditary
syndromes, including Von Hippel–Lindau, multiple
endocrine neoplasia-1 (MEN-1), neurofibromatosis
type 1 and tubular sclerosis.
42
Clinical presentation
The mode of presentation is dependent on the
functional state of the tumour. Non-functioning
tumours may present incidentally, whereas symptoms
are usually related to mass effect or the presence of
metastatic disease. For those tumours associated
with a syndrome, this will be related to the specific
hormone produced (Table17.2).
40
of
Investigations
The order of investigations will be dependent on
presentation. The general principle for functional
tumours is to confirm the diagnosis (biochemically)
prior to localisation (radiologically).
Biochemical
Specific fasting gut hormones can be measured for
functional tumours but testing is complex and subject
to change, therefore it is recommended that when
faced with the need to investigate such a patient
current guidelines are reviewed and the recommended
tests are performed in centres with significant
experience.
including those with non-functional tumours, serum
chromogranin A (protein produced from cells arising
from the neural crest) will be elevated.
chromogranin A is sensitive, it is not highly specific
and those interpreting the test must be aware of causes
of false-positive results.
chromogranin A has been shown to correlate with
burden of disease (although not with gastrinomas),
response to treatment and recurrence.
Other investigations, such as calcium, parathyroid
hormone, calcitonin and thyroid function tests,
should also be considered, particularly if there is a
history that suggests MEN-1.
a hereditary component is suspected, referral to an
appropriate genetic service for further investigation
should be initiated.
Radiology
For non-functioning tumours, where localisation is
often not an issue, a high-quality arterial and portal
venous phase CT will be sufficient to direct therapy,
particularly in determining if surgery is indicated.
Features suggestive of a PNET on CT include the
presence of a hypervascular or hyperdense lesion
within the pancreas; however, they can also appear
cystic or contain calcifications.
large incidental mass within the pancreas, particularly
without vascular encasement or desmoplastic reaction,
should also alert the clinician to the possibility of a
PNET.
Although somatostatinomas, VIPomas and
glucagonomas tend to be large and easily identified
and staged by contrast-enhanced CT, this is often not
the case for insulinomas and gastrinomas, unless there
is widespread metastatic disease. Most insulinomas
are <
hypervascular (Fig.17.4) with either uniform or target
enhancement; however, given that they are often noncontour-conforming, detection of the vascular blush
is essential to localise them (the chance of detection
can be maximised by timing the images 25 seconds
after contrast injection).
43
In the majority of patients with PNETs,
41
Although
43
The degree of elevation of
43
41
For those in whom
44
The presence of a
44
2 cm and solitary. On CT they tend to be
44
MRI features include low
292
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Cystic and neuroendocrine tumours of the pancreas
Table17.2 • Presentation, diagnosis and initial medical management of functional pancreatic neuroendocrine tumours
Medical options
for initial symptom
Tumour type Syndrome Symptoms Diagnosis
control
Insulinoma Whipple's triad Neuroglycaemic or
neurogenic symptoms
relieved with eating
Gastrinoma Zollinger–Ellison Complicated peptic
ulceration or gastrooesophageal reflux,
diarrhoea, abdominal
pain
Glucagonoma Glucagonoma syndrome Necrolytic migratory
erythema, weight loss,
diabetes mellitus,
stomatitis, diarrhoea,
thromboembolism
VIPoma Verner–Morrison
syndrome
Profuse watery
diarrhoea, hypokalaemia
Somatostatinoma Gallstones, steatorrhoea,
hypochlorhydria, glucose
intolerance
Carcinoid Carcinoid syndrome Abdominal pain, if
metastases then
flushing, palpitations,
rhinorrhoea, diarrhoea,
bronchospasm, pellagra
Insulin:glucose ratio
>0.3 in presence of
hypoglycaemia
C-peptide suppression
Overnight feeding
Diazoxide titrated to
symptom resolution
Somatostatin analogue
test
Serum fasting gastrin
>
1000 pg/mL (if gastric
pH <2.5)
High-dose proton pump
inhibition (may require
up to 60 mg b.d.)
Secretin stimulation test
Plasma glucagon
>
1000 pg/mL
Somatostatin analogue,
hyperalimentation,
thrombosis prophylaxis
Plasma VIP >
1000 pg/
Somatostatin analogue
mL
Raised plasma
somatostatin
24-hour urinary 5-HIAA Somatostatin analogue
signal intensity on T1-weighted images and they are
particularly well seen on fat-suppressed (T1- and
T2-weighted) images.
44
In contrast to insulinoma,
gastrinoma can be multiple and extrapancreatic
(located within the gastrinoma triangle; the junction
between neck and body of the pancreas medially, the
junction of the second and third parts of the duodenum
inferiorly and the junction of the common bile duct and
cystic duct superiorly).
they tend to be less vascular than insulinoma.
is a high rate (70–80%) of lymph node and hepatic
metastases.
of gastrinoma is related to size and can be as low as
30–50%.
44
The sensitivity of CT in the detection
45
Although slightly better figures have been
45
On radiological examination,
44
There
reported for insulinomas, this can be increased to 94%
with the use of thin formats and, with the addition
of endoscopic ultrasound, sensitivities of 100% have
been reported.
45
Endoscopic ultrasound is particularly useful for
imaging the duodenal wall, regional lymph nodes and
the pancreatic head, and has reported sensitivities of
79–100%, but is operator-dependent.
45
Equally, the
use of intraoperative ultrasound has also been shown
to be useful, particularly in gastrinomas, by identifying
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occult multiple primaries or metastatic disease. The
sensitivity for detecting small lesions in the pancreatic
head is reported to be as high as 97%.
45
PNET hepatic metastases often appear as lowattenuation lesions on pre-contrast CT and hypervascular lesions on post-contrast imaging.45 It is,
however, important to perform a hepatic arterial
phase as they can be isointense with normal
parenchyma on portal venous imaging. MRI
appearances of hepatic metastases are usually of
low signal intensity lesions on T1- and high signal
intensity on T2-weighted images. Importantly, 15%
of hepatic metastases were only seen on immediate
post-gadolinium imaging.
In addition to standard radiological imaging,
somatostatin receptor scintigraphy (SRS) is also
very useful in the staging and treatment of PNETs
(with the exception of insulinomas).
43
SRS works
on the principle that PNETs express somatostatin
receptors. The use of a somatostatin analogue
labelled with a radioactive isotope (of which there
are several) allows a functional image to be obtained
but it requires somatostatin analogues to be stopped
prior to the scan. As a single investigation, it is
293

Chapter 17
Figure17.4 • A 78-year-old man presented with neuroglycaemic symptoms. Biochemical testing confirmed an insulinoma.
Arterial phase computed tomography revealed a hypervascular lesion in the tail of the pancreas (black arrow). Laparoscopic
spleen-preserving distal pancreatectomy was performed. Histology confirmed malignant, node-positive neuroendocrine
tumour consistent with an insulinoma. After 4years with no symptoms the patient re-presented with symptoms of
hypoglycaemia. Further investigation revealed an isolated nodal recurrence adjacent to the superior mesenteric artery. The
patient underwent a completion radical antegrade modular distal pancreatico-splenectomy with resolution of hypoglycaemic
symptoms.
probably the most sensitive for the detection of
Treatment
PNETs; however, equivalence can be achieved
with a combined approach of standard radiology
(particularly MRI and EUS), which has the advantage
of providing a detailed anatomical analysis.
46
SRS
does, however, offer the advantage of reflecting
functionality, which is important if treatment
doses of radiolabelled somatostatin analogues or
meta-iodobenzylguanidine (MIBG) are to be used.
18
F-labelled deoxyglucose PET has not been shown
to be useful for the majority of PNETs; however, the
development of newer alternatives to
18
F-labelled
deoxyglucose would appear to be promising.
Invasive investigations such as selective arterial
calcium (insulinoma) and secretin (gastrinoma)
stimulation with hepatic/portal venous sampling are
not used routinely and are undertaken only if there is
a high suspicion but non-invasive imaging has failed
to localise the tumour.
43
Once the diagnosis of a functioning tumour is
established, control of the hormonal excess is
the first priority in minimising symptoms and
complications. Medications used for each individual
tumour are shown in Table 17.2. Somatostatin
analogue infusions are recommended pre- and
intraoperatively for carcinoid tumours to prevent
carcinoid crisis.
41
Surgery offers the only chance of
cure for those with localised disease. The approach
is dependent on tumour type and the presence or
46
absence of an inherited syndrome.
43
The specific
management of hereditary PNETs is beyond the
remit of this chapter and readers are referred to more
detailed reviews for an in-depth discussion.
Over 80% of localised sporadic insulinomas are
solitary, benign and <
2 cm in size, making them ideal
for consideration of enucleation and laparoscopic
42,47,48
294
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Cystic and neuroendocrine tumours of the pancreas
resection.43 Enucleation is considered possible if the
lesion can be clearly localised pre- or intraoperatively
and if the relationship to the pancreatic duct has
been clearly identified.
has been shown to be particularly valuable in
helping to assess these factors.
histological confirmation of the benign nature
must be established.
tumours where malignancy is suspected (hard,
infiltrating tumour, duct obstruction or lymph node
involvement), if there is major vascular involvement
or the tumour is large.
for resection as for any pancreatic tumour. However,
if a distal pancreatectomy is being performed,
attempts to preserve the spleen should be made.
Blind pancreatic resection should be avoided.
Ablative therapies may also be appropriate in
selected patients.
For localised sporadic gastrinoma, surgery
has been shown to increase survival.
Duodenotomy and intraoperative ultrasound
com bined with palpation (sensitivity 91–95%) are
the key to successful intraoperative localisation.49
For duodenal gastrinomas, small tumours (<
can be enucleated from the submucosa while larger
tumours require full-thickness excision.
pancreatic gastrinomas, intraoperative assessment
regarding the suitability for enucleation (similar
to that described above for insulinomas) should
be performed. However, if the tumour is not
suitable, a formal pancreatic resection (pancreaticoduodenectomy) should be performed. It is now
recommend that formal oncological lymph node
dissection be performed due to high rates of
involvement and possible survival benefit.
Most localised non-functioning tumours are
detected at such a size that enucleation is not
feasible, but given the increasing use of crosssectional imaging and the earlier detection of
smaller lesions, enucleation is likely to become
a more frequent possibility. For asymptomatic
suspected benign, non-functioning PNETs, it has
been recommended that tumours <
safely observed.43 The risk of malignancy is related
harbour malignant potential (Fig.17.5).50 Currently,
patients should be assessed regarding fitness for
surgery and an informed decision made with the
patient regarding resection or observation. Central
pancreatectomy has also been shown to be feasible
for selected tumours and has the advantage of
reducing the risk of postoperative diabetes.
formal resection with lymphadenectomy should
be performed for suspected malignant tumours as
lymph node metastases are common (27–83%).
43
Intraoperative ultrasound
47
Postoperatively,
41
Resection is required for
47
Patients should be assessed
43
48
47
47
5 mm)
49
For
43
2 cm can be
51
A
50
Figure17.5 • A 30-year-old female with Von Hippel–
Lindau disease underwent pancreatic screening.
Radiological imaging revealed five neuroendocrine
tumours within the pancreatic head. Pancreaticoduodenectomy was performed. Pathological sectioning
of the pancreatic head revealed multiple neuroendocrine
tumours (PNET), including at least one well-differentiated
pancreatic endocrine carcinoma (node-positive) and a
well-differentiated duodenal endocrine carcinoma (DC).
All tumours were between 12 and 18 mm diameter. An
incidental serous cyst adenoma (SCA) was also identified.
Resection is the treatment of choice for symptomatic
patients with localised disease.
50
The median survival
following resection was reported as significantly
longer than for patients with metastatic or locally
advanced unresectable disease (7.2 years vs 2.1 vs
5.2 years).50 Importantly, however, 48% of patients
who underwent resection for localised disease
developed recurrence at a median follow-up of
2.7 years.50 Because of the long natural history of
these tumours and given that many are symptomatic
and difficult to palliate without resection (e.g.
tumour bleeding), the criteria for what determines
unresectable disease may not be the same as those for
adenocarcinoma of the pancreas. The MD Anderson
experience would suggest that, in high-volume centres,
major venous reconstruction can be performed safely,
but only rarely should arterial reconstruction (isolated
hepatic artery involvement) or upper abdominal
exenteration be performed, due to the associated high
long-term morbidity.
50
In addition, a recent report
has also indicated that an incomplete resection (R2)
is associated with a high perioperative mortality and
may in fact be detrimental to the patient's survival.
Metastatic disease
Only 10% of patients with hepatic metastases will
be suitable for potentially curative resection.
However, it would appear that although recurrence
rates are high, a survival advantage can be
achieved, although randomised data are lacking.
Synchronous cholecystectomy should be performed
52
41
53
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295

Chapter 17
to reduce complications from adjuvant therapy
such as somatostatin analogues and hepatic artery
embolisation.
53
For patients with non-functioning
unresectable metastatic disease, there is no evidence
to support palliative or ‘debulking’ resections, with
possibly the only exceptions being those who have
significant local symptoms from the primary and
low-volume hepatic metastases.
50
For those with
obstruction of the gastrointestinal or biliary tract,
surgical bypass should be the first-line treatment
in those with well-differentiated disease, given the
indolent nature of the disease.
A cytoreductive approach (surgery or ablative
therapies) has been advocated in patients with
hormonal excess and hepatic metastases if 90% of
tumour bulk can be removed, although randomised
trials are lacking.
documented in the UK and European guidelines on
the management of metastatic PNETs included
somatostatin analogues (short- and long-acting),
interferon-α, hepatic artery embolisation,
radiolabelled analogues (MIBG and somatostatin),
liver transplantation and radiofrequency ablation.
41,43
Other options assessed
53
41,54
Systemic chemotherapy for PNETs has been based
around streptozocin and 5-fluorouracil after a
randomised trial in 1979 showed a survival advantage
for patients with metastatic carcinoid tumours
receiving combination chemotherapy.
55
However,
given the side-effects and variable behaviour of
PNETs, it has not been widely accepted into clinical
practice. More recently there is increased interest in
the use of temozolomide-based chemotherapy.
Two recent placebo-controlled randomised
trials using the novel agents sunitinib56 and
everolimus57 have shown an increase in overall and
progression-free survival, respectively. In addition, a
placebo-controlled trial of lanreotide in patients with
enteropancreatic NETs has shown evidence of
antiproliferative activity.58 Thus, the results of these
three trials would suggest these treatments should
represent the standard of care.
The therapeutic options for patients with metastatic
disease continue to evolve. It is clear that decisionmaking is complex and dependent on tumour and
patient factors. It is strongly recommended that
management decisions for these patients are made
in a multidisciplinary forum.
54
Pathology and outcome
PNETs are classified into four groups based on a
combination of clinical, histological and molecular
features.
classified as well-differentiated endocrine tumours
41
Tumours confined to the pancreas are
that can be subdivided into those of benign behaviour
2 cm size, <2 mitoses per 10 high-power fields
(<
(HPFs), Ki67 index <2% and no vascular invasion)
or uncertain behaviour (if the above criteria are
not met). Tumours not confined to the pancreas
(gross local invasion or metastases) or that exhibit
evidence of small-cell carcinoma are considered
endocrine carcinoma, which are further subdivided
into well-differentiated (well to moderately
differentiated (mitotic rate 2–10 per 10 HPFs, Ki67
index >5%) or poorly differentiated (small-cell
carcinoma, necrosis, >10 mitoses per 10 HPFs, Ki67
index >15%, prominent vascular and perineural
invasion). Importantly, the diagnosis of functional
tumours is not made histologically but clinically, as
immunohistochemical staining of specific hormones
does not correlate with the clinical picture.
41
In 2010,
the seventh edition of the American Joint Committee
on Cancer (AJCC) published its first TNM staging
classification for PNETs.
et al. retrospectively applied the staging system to
a dataset of 425 patients with PNETs.
59
Using this, Strosberg
60
Five-year
overall survival for stages I–IV was 92%, 84%, 81%
and 57%, respectively, thus indicating the proposed
system is a useful adjunct for classifying PNETs.
Other tumours
The other two main types of cystic neoplasms are
serous (SCA) and mucinous (MCN) cystic neoplasms.
Because of the difference in malignant potential,
the management of these two tumours differs, yet
clinically and radiologically there is considerable
overlap. It is therefore useful to contrast and
compare them. The exact incidence of serous and
mucinous cystic tumours is unknown; however, in
a retrospective review of 24 039 patients undergoing
radiological imaging, 0.7% had pancreatic cystic
neoplasms. Of the 49 (0.2%) who underwent surgery,
10 and 16 patients had a final diagnosis of SCA and
MCN, respectively.
retrospective study reported on 2622 patients with
62
The median age at diagnosis was 58years,
SCA.
with 74% occurring in women. Sixty-one percent
of patients were asymptomatic. SCA were evenly
distributed throughout the pancreas. In contrast,
MCNs are almost exclusively found in women,
with a peak incidence in the fifth decade, and are
more likely to be located within the tail.
also commonly associated with Von Hippel–Lindau
syndrome
42
(Fig.17.5), and young patients presenting
with multiple cystic lesions involving the pancreas
and kidneys should be genetically assessed.
On cross-sectional imaging, the four typical
appearances of SCA were microcystic (45%; multiple
<2-cm cysts), macrocystic (32%; multiple >2-cm
cysts), mixed type (18%; variable-sized cysts) and solid
61
A recent large multinational
63
SCAs are
64
296
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Cystic and neuroendocrine tumours of the pancreas
(5%; no cysts visible on cross sectional imaging).62
Central calcification (so-called sunburst calcification)
occurred in 15%. When the classic features are
present, differentiation from other tumours is not
difficult; however, the presence of a uni- or oligolocular
macrocystic (>
2 cm) lesion is more difficult to
diagnose and a wide differential exists. Both SCAs
(oligocystic type) and MCNs can fall into this group,
although MCNs are less likely to be multilocular and,
if calcification occurs, it does so peripherally and may
be a marker of underlying malignancy.
65
The presence
of solid components within a cystic lesion indicates
the presence of, or high-risk of, malignancy and
therefore surgical resection should be considered.
65
Included within this differential would be PNET,
solid pseudopapillary neoplasm (young women)
or mucinous cyst adenocarcinoma.
for either SCAs or MCNs to communicate with the
pancreatic duct, but it has been reported.
65
It is unusual
65
The ability of non-interventional imaging to
obtain an accurate diagnosis is limited. In a report
of 100 SCAs from Bassi etal., the correct diagnosis
was achieved in 53%, 54% and 76% by ultrasound
(US), CT and MRI, respectively.
66
An incorrect
diagnosis was made in 31%, 34% and 26%, and
the investigation was non-diagnostic in 16%, 12%
and 0% with US, CT and MRI, respectively.
In a study of solitary cystic (IPMNs were excluded)
neoplasms, 71 patients underwent EUS and fluid
aspiration (for mucin, viscosity, amylase, lipase, CEA,
CA19-9, cytology) followed by surgery to assess its
accuracy.
67
The authors concluded that an accurate
algorithm using measurement of viscosity, lipase
and CEA can be used to determine the diagnosis of
cystic lesions. A viscosity of ≥1.6 indicates an MCN
and the patient should be offered resection. If it is
<1.6 and the lipase is <
6000 U/mL, this indicates an
SCA. If the viscosity is <1.6 and lipase is > 6000 U/
mL, then a CEA measurement should be performed,
and if this value is less than 480 U/mL the diagnosis
is a pseudocyst. If it is >480 U/mL, a repeat EUS
and fine-needle aspiration should be performed
in 3–6 months. Using this algorithm, only 2 of 71
patients that underwent resection for suspected
MCN had a final histology revealing a pseudocyst.
The management of SCAs and MCNs differs
based on their malignant potential. SCAs rarely
undergo malignant transformation and if
asymptomatic, no intervention is required.62 Patients
with significant symptoms may be offered resection.62
Until recently it was recommended that all suspected
MCNs undergo resection because of their malignant
potential.2 However, more recent series
shown that it is safe to observe lesions less than
3 cm without mural nodules, thus aligning
management with BD-IPMN.
68,69
have
Pathologically, SCAs demonstrate monomorphous
cuboidal-shaped epithelium. The cells are glycogenrich with cellular cytoplasm and small regular
nuclei. There is a lack of mitotic activity. The cysts
appear ‘empty’ on microscopy. In contrast, the cyst
content of MCNs is turbid and tenacious,
64
and
microscopically (unlike SCAs) the cyst lining can
be highly variable. The cells are mucin-producing,
which can be a single cell layer of flattened
cuboidal epithelium or contain papillary tufting.
64
The tumours are classified as benign, borderline
or malignant depending on the nuclear features of
the cells.
tumour as malignant invasion can occur without
the presence of a mass.
64
It is important to examine the whole
64
The unique feature of
MCNs, however, is the presence of ovarian stroma
(highly cellular, densely packed, plump spindle cells).
Current recommendations require the presence of
this for a tumour to be classified as a MCN.
particularly important when the differential includes
IPMN, in which this type of stroma is not seen.
2
This is
2
Key points
• As the use of cross-sectional imaging has become more frequent, there has been an increase in the
diagnosis of cystic neoplasms within the pancreas.
• Main-duct IPMNs should be resected due to the high incidence of underlying malignancy; however,
a selective approach to intervention for side-branch IPMNs should be taken (dependent on the
presence of symptoms, tumour markers and tumour characteristics).
• Investigation and follow-up of cystic lesions of the pancreas requires a multimodal approach, of
which endoscopic ultrasound with biopsy is becoming an increasingly important component.
• While asymptomatic SCAs do not require intervention, some MCNs should be resected due to their
underlying malignant potential.
• The management of PNETs will be dependent on the presence or absence of an underlying genetic
syndrome, whether the tumour is hormonally active, and stage of disease.
• New adjuvant therapies have been shown to increase progression-free survival in patients with
advanced neuroendocrine tumours.
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297

Chapter 17
Recommended videos:
• Laparoscopic radical antegrade
pancreatosplenectomy – https://tinyurl.com/yc3jgg9k
(IHPBA members only)
• Laparoscopic pancreaticojejunostomy during
laparoscopic pancreaticoduodenectomy –https://
tinyurl.com/y9gtsmwn
• University of Toronto video atlas of pancreatic
techniques and procedures – https://tinyurl.com/
ya96srgv
Full references available at http://expertconsult.
inkling.com
Key references
2. TanakaM, Fernandez-del CastilloC, AdsayV, etal.
International consensus guidelines for management
of intraductal papillary mucinous neoplasms
and mucinous cystic neoplasms of the pancreas.
Pancreatology 2012;12:183–97. PMID: 22687371.
This international guideline outlines a detailed
management strategy for the IPMN and MCN of the
pancreas. Importantly it differs in its recommendations
from the AGA guidelines.
23. Vege SS, Ziring B, Jain R, et al. and Clinical
Guidelines Committee. AGA Institute guideline on
the diagnosis and management of asymptomatic
neoplastic cysts. Gastroenterology 2015;148:819–
22. PMID: 25805375.
This highly controversial paper presents a sound
methodological approach to the available evidence
for the management of incidental pancreatic cystic
neoplasms. It recommends a conservative approach to
investigation and follow-up with stopping points due to
the lack of supporting evidence and potential to do harm.
28. Falconi M, CrippaS, ChariS, etal. Quality and
assessment of the guidelines on cystic neoplasms
of the pancreas. Pancreatology 2015;15:463–9.
PMID: 26100659.
This paper examines the quality of the published
guidelines on pancreatic cystic neoplasms. It highlights
the deficits of the current literature and tries to achieve
expert consensus on clinically important questions.
48. NortonJA, FrakerDL, AlexanderHR, etal. Surgery
increases survival in patients with gastrinoma. Ann
Surg 2006;244:410–9. PMID: 16926567.
In a study of 160 patients with gastrinomas, 35 patients
(with similar staged localised disease) who did not
undergo resection were compared to those who
underwent resection. After 12 years' follow-up, 29%
of those who did not undergo surgery had developed
hepatic metastases compared to 5% in the resected
group (P <0.001).
56. RaymondE, DahanL, RaoulJL, etal. Sunitinib malate
for the treatment of pancreatic neuroendocrine
tumors. N Engl J Med 2011;364:501–13. PMID:
21306237.
One hundred and seventy-one patients with advanced
and progressive PNETs were randomised in doubleblind fashion to placebo or sunitinib. The trial was
stopped early due to increased complications and
death in the placebo group. An improved progressionfree survival (11.5 vs 5.5 months, P <0.001) and reduced
risk of death (105 vs 255, P
treatment group.
= 0.02) were seen in the
57. Yao JC, Shah MH, Ito T, et al. Everolimus for
advanced pancreatic neuroendocrine tumours. N
Engl J Med 2011;364:514–23. PMID: 21306238.
In a placebo-controlled randomised crossover design
trial, 410 patients with advanced and progressive
PNETs were enrolled to placebo or everolimus. In those
patients who received everolimus there was a 65%
reduction in risk of progression (median progressionfree survival was 11months vs 4.6 months) as compared
to placebo. In addition, tolerance was high.
62. Jais B, Rebours V, Malleo G, et al. SCN of the
pancreas: a multinational study of 2622 patients.
Gut 2016;65:305–12. PMID: 26045140.
This large multinational study reported on 2622 patients
with serous cystadenomas accumulated over three
decades. The key points were: asymptomatic patients
do not need resection and disease-specific mortality is
extremely rare.
298
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18
Hepatobiliary and pancreatic trauma
Adam Brooks
Alex P. Navarro
Introduction
Hepatobiliary and pancreatic trauma represents
one of the most challenging scenarios faced by
specialist surgeons. Equally, the non-specialist will
find such situations daunting due to the anatomical
complexity of the region. Despite this, with a
modern approach excellent outcomes are achievable
in nearly all grades of hepato-pancreato-biliary
(HPB) organ injury. The key factors required are
meticulously accurate assessment of injury through
imaging or at initial laparotomy, basic damage
control manoeuvres performed with anatomical
respect and understanding, and finally, definitive
surgery undertaken by specialist HPB surgeons in
complex cases.
This chapter will address the presentation,
initial assessment and management of patients
with liver, biliary and pancreatic injuries. The
selection criteria for non-operative management
will be discussed together with the indications for
operative intervention. The factors guiding surgical
options and decision-making will be examined. The
spectrum of complications and likely outcomes
following trauma will also be reviewed. The
American Association for the Surgery of Trauma
Organ Injury Scale (OIS) provides a description
of the injury categorised from minor injury (grade
1) to severe injury (grade 6). The primary concern
of the surgical team managing a trauma patient
is the patient’s physiological status and this will
determine surgical management; however, the
OIS allows guidance based on available evidence
for the management of liver, biliary and pancreas
injuries.
Liver trauma
The liver is the most frequently injured organ in
abdominal trauma.
injuries was noted by J. Hogarth Pringle in his
seminal monograph published in 1908, where he
commented ‘Rupture of the liver is fortunately an
accident not often met with, but one which may be
associated with a condition of the patient as serious
as any one can meet with in surgical practice’.
capacity for torrential haemorrhage from the liver
means that the patient can quickly enter a vicious
cycle of physiological derangements consisting of
coagulopathy, hypothermia and metabolic acidosis,
rapidly leading to death.
severe hepatic injury by Asensio
exsanguination accounted for 54% of deaths.
Mechanisms of liver injury
The liver can be injured by two principal injury
mechanisms: blunt and penetrating trauma. Motor
vehicle crashes account for the majority of blunt
injuries, whereas gunshot wounds and stabbings
constitute the major cause of penetrating injuries.
A 2017 review of 10years of outcomes for hepatic
trauma in the UK showed that, of 4368 cases of
hepatic trauma, 81% were caused by blunt injuries
with 19% due to penetrating trauma.
typical for other European centres,
the experience in South Africa, where penetrating
injuries account for 66% of liver trauma,
North America, where up to 86% of liver injuries
are penetrating wounds.
1
The serious nature of liver
2
The
3
A review of 7454 cases of
4
8,9
in 1990 found that
5
6
it differs from
4
Whilst this is
7
and in
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299

Chapter 18
Blunt liver trauma may be divided accord ing to
the mechansism of injury: deceleration (shearing)
and crush injury. Deceleration injuries tend to
occur in road traffic crashes and falls from a
height where there is rapid forceful movement
of the liver relative to its fixed diaphragmatic
attachments.
10
Crush injuries are caused by direct
trauma to the liver area. The two types of injury
may coexist, but tend to produce somewhat
different types of liver injury. Deceleration or
shearing injuries create lacerations in the hepatic
parenchyma, typically between the right posterior
section (segments 6 and 7), the right anterior
section (segments 5 and 8), and the right/left liver
plane (segments 5/8 vs segment 4A/4B) which can
extend to involve major vessels. In contrast, a
direct blow to the abdomen may lead to a crush
injury, with damage to the central portion of the
liver (segments 4, 5 and 8). Compression between
the right lower ribs and the spine may also cause
bleeding from the caudate lobe (segment 1). Blunt
trauma can rupture Glisson's capsule and can
also lead to subcapsular or intraparenchymal
haematoma formation.
Penetrating injuries are usually associated with
gunshot or stab wounds, with the former usually
resulting in more tissue damage due to the cavitation
effect as the bullet traverses the liver substance.
Injury to the hepatic veins and juxtahepatic vena
cava can occur as a result of shearing stress in
blunt trauma. Typically such injuries are associated
with rapid pre-hospital death. However, it is worth
noting that there may not be initial exsanguinating
haemorrhage if the weight of the liver provides
sufficient compression against the retroperitoneum
allowing tamponade.
Classification of liver injury
The severity of liver trauma ranges from a minor
capsular tear, with or without parenchymal injury,
to extensive disruption involving both lobes of
the liver with associated hepatic vein or vena
caval injury. The American Association for the
Surgery of Trauma has adopted for general use
the classification of liver injury described initially
in 1989 by Moore and colleagues, and revised
subsequently in 1994
injury grade is calculated from assessment of
the liver injury using information derived from
radiological study, operative findings or autopsy
report. Where there are multiple injuries to the
liver, the grade is advanced by one stage. As stated
previously, it is the physiological status of the
patient rather than the anatomical grade of injury
that dictates management. Grade I–III injuries
are considered minor; they represent 80–90% of
all cases and the majority can be managed nonoperatively. Grade IV–V injuries are considered
severe injuries and non-operative management or
surgical intervention can be applied depending on
the patient’s physiology and clinical progression.
Grade VI lesions are generally regarded as
incompatible with survival.
The initial assessment of an injured patient
should be performed according to Advanced
Trauma Life Support (ATLS) protocols developed
by the American College of Surgeons Committee
on Trauma. A rapid primary survey should be
completed to identify immediately life-threatening
injuries that require emergency intervention.
Simultaneously, adequate intravenous access should
be established to allow resuscitation to begin.
11
(Table 18.1). The hepatic
Table18.1 • Hepatic injury scale used by the American Association for the Surgery of Trauma
Grade* Description
I Haematoma Subcapsular, <10% surface area
Laceration Capsular tear, <
1 cm parenchymal depth
II Haematoma Subcapsular, 10–50% of surface area
Laceration Intraparenchymal <
10 cm in diameter, 1–3 cm parenchymal depth, <10 cm in length
III Haematoma Subcapsular, >50% surface area or expanding; ruptured subcapsular or parenchymal haematoma;
intraparenchymal haematoma >
10 cm or expanding
Laceration >3 cm parenchymal depth
IV Laceration Parenchymal disruption involving 25–75% of hepatic lobe or 1–3 Couinaud segments within a
single lobe
V Laceration Parenchymal disruption involving >75% of hepatic lobe or >3 Couinaud segments within a
single lobe
Vascular Juxtahepatic venous injuries – retrohepatic cava, major hepatic veins
VI Vascular Hepatic avulsion
*Advance one grade for multiple injuries up to grade II.
300
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Hepatobiliary and pancreatic trauma
Current resuscitation strategies advocate haemostatic
resuscitation and the transfusion of 1:1:1 blood,
fresh frozen plasma and platelets.
protocols based on ‘Damage control’ principles are
encouraged.
13
12
Techniques and
Diagnosis of liver injury
In penetrating abdominal trauma, hepatic injury
should be considered in any patient with a wound
to the abdomen. Hepatic injury should also be
considered in patients with penetrating low thoracic
wounds (it is important to be aware that the liver
anteriorly is situated at the level of the nipple)
and also in posterior penetrating wounds below a
coronal plane at the tips of the scapulae.
Patients with major hepatic injury may present with
profound clinical shock and abdominal distension.
Hypotension resistant to fluid resuscitation
combined with gross abdominal distension remains
an indication for immediate laparotomy. The
operative management options for patients in this
situation will be discussed in detail subsequently.
Emergency room thoracotomy with cross-clamping
of the descending thoracic aorta is a dramatic but
sometimes necessary intervention for exsanguinating
abdominal haemorrhage.
The Eastern Association for the Surgery of Trauma
(EAST) published practice guidelines for Emergency
Department thoracotomy in 2015,
meta-analysis of 72 studies that included 10 238
patients. This EAST study showed that overall
survival rate for patients with penetrating thoracic
trauma and signs of life on arrival at hospital was
21.3%, with a neurological intact survival of 11.7%.
In patients with penetrating thoracic trauma with
no signs of life on arrival at hospital, the survival
rate was 8.3%, with a lower neurologically intact
survival rate of 3.9%.
The outcomes for blunt injuries are worse. The
survival rate of blunt trauma patients with signs of
life on arrival at hospital is 4.6% and a neurological
intact survival rate of 2.4%. Blunt trauma patients
with no signs of life on arrival have an extremely
poor survival rate of 0.7%. In the EAST analysis, one
patient survived neurologically intact to discharge
after blunt injury traumatic arrest with no signs of
life out of 825 patients who underwent resuscitative
thoracotomy in the Emergency Department.
REBOA (Resuscitative Endovascular Balloon
Occlusion of the Aorta) is a technique where
a balloon catheter is inserted into the femoral
artery and the balloon inflated within the aorta
to control distal bleeding. Relatively limited data
exist to support its widespread deployment in
the exsanguinating trauma patient; however, the
technique is rapidly gaining interest.
14
based on a
14
15,16
Emergency room thoracotomy remains a
potentially life-saving manoeuvre in patients with
significant injury. However, these patients are better
served by rapid transport to the operating theatre.
Patients who are haemodynamically stable or
respond to resuscitation should undergo appropriate
imaging to determine the nature and extent of their
injuries. Collateral history from the emergency
services is invaluable – photos of the scene give
information regarding the mechanism and likely
injury pattern. Conscious patients may complain
of abdominal pain. Shoulder tip pain may arise
from blood in the subdiaphragmatic space causing
phrenic nerve irritation.
Clinical signs may be detected during the initial
examination including anterior abdominal wall
bruising, which may indicate compression from a
seatbelt, and flank bruising, which may indicate
retroperitoneal extravasation of blood. Signs of
localised or generalised peritonitis are recorded
in the conscious patient. Baseline investigations
consist of a full blood count (for haemoglobin and
haematocrit), serum urea and electrolytes, liver
function tests, a coagulation screen, and blood for
crossmatching. It will often be necessary to activate
local Major Transfusion Protocols. Following
initial assessment, patients who are conscious
but have haemodynamic instability with clinical
signs of peritonitis should undergo laparotomy.
In patients who are haemodynamically stable
and have suspected liver injury, further diagnostic
tests may be undertaken at this stage to define the
nature of the injuries. An ideal test will establish
the presence and extent of any liver injury together
with providing information on concomitant
visceral injury.
Formerly, diagnostic peritoneal lavage (DPL) was
the procedure of choice for the quick diagnosis of
haemoperitoneum, particularly in patients with
an impaired level of consciousness and equivocal
physical signs. However, DPL is invasive and a
positive result for blood provides no information
regarding either the site or the nature of the injury,
and in the context of liver injury may lead to patients
undergoing surgery where they may be better treated
non-operatively.
An alternative investigation advocated in initial
trauma evaluation is Focused Assessment with
Sonography for Trauma (FAST).
17
This involves
ultrasonographic assessment of the pericardium, right
upper quadrant including Morrison's pouch, left upper
quadrant and pelvis. This evaluation is not designed
to identify the degree of organ injury, but rather the
presence of blood. A large meta-analysis of the use
of emergency ultrasonography for blunt abdominal
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