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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_1841_Библиотеки_им_академика_М_И_Перельмана.pdf
PANCREATITIS
53
Endocrine tumours can be benign or malignant, functioning or non-
functioning, and occur sporadically or as part of a multiple endocrine neopla-
sia (MEN) syndrome (Metz and Jensen, 2008 ). The investigation can be
difficult because of the potential locations and frequently small size, unusual
symptoms over a long period, and the occurrence of a significant number of
non-functioning lesions. When deciding on the investigation and manage-
ment of these tumours, all these factors have to be considered and they
must be managed in a multidisciplinary setting, involving endocrinologists,
diabetologists, and oncologists ( Fig. 1.37 ).
Interventional radiology is also valuable to identify the site of the tumours,
demonstrate that they are functioning, and occasionally provide therapeutic
options. Surgery is employed at each end of the spectrum that encompasses
these tumours. Single, solid, non-functioning lesions or multiple lesions in
MEN syndromes can be excised for a cure while, at the other end of the spec-
trum, surgery is employed for debulking or symptom control when other
measures have failed (Halfdanarson et al ., 2008 ).
Table 1.7 WHO classification of neuroendocrine tumours
1980 2000
Approximately 90% carcinoids:
GI endocrine tumours
Approximately 10% other tumours:
Paraganglioma and neuroblastoma
Medullary thyroid carcinoma
Chromophobe pituitary adenoma
Small cell lung cancer
Merkel cell skin cancer
All neuroendocrine tumours classifi ed on
the basis of:
Site of origin:
GI tract
Pancreas
Lung
Thyroid
Pituitary
Others
Malignant potential:
Benign
Benign or low grade malignant (uncertain)
Malignant (uncertain)
Low malignant
High malignant
Functional activity:
Functioning
Non-functioning
PANCREAS
54
Fig. 1.37 Investigation and management of a suspected gastroenteropancreatic neuroendocrine (GEP–NET) tumour.
Suspected
gastroentereopancreatic
neuroendorcrine tumour
Exclude inherited
disorder
Non-resectable
Resectable
Metastases
Metastases
inoperable
Metastases
operable
No metastases
Metastases
No metastases
Surgery
No residual
disease
Transplantation
Residual disease
Functioning
secretory
Treatment
options
Non functioning
Radio-nucleide
somatostatin analogue
chemotherapy
interferon alpha
new drug trial
Regular follow-up
Observation
Debulking and
ablation
Embolization/
chemoembolization
radio-nucleide
embolisation
Chemotherapy/
palliative care
Mainly hepatic
Biochemical studies
24hr urinary 5HIAA
plasma chromogranin A
gut hormone profile
imaging ± biopsy
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55
Table 1.8 Malignant potential of the neuroendocrine tumours
Differentiation Malignant potential Functional activity and example
Well differentiated Benign
Benign or low-malignant
(uncertain) potential
Low malignant
Functioning (insulinoma)
Non-functioning
Functioning (gastrinoma, insulinoma,
glucagonoma, somatostatinoma,
VIPoma, or ectopic hormone
syndrome tumour)
Functioning (gastrinoma, insulinoma,
glucagonoma, somatostatinoma,
VIPoma, or ectopic hormone-
producing tumour)
Non-functioning
Poorly differentiated High-grade malignant Anaplastic small-cell carcinoma
The morbidity produced by these tumours when functioning is significant
and in particular, the most common type, the insulinomas, can produce fatal
consequences or disabling morbidity. Patients frequently have to be admitted
for dextrose infusions while their tumours are located. Locating all these
tumours can be difficult if they are small (and a number occur outside the
pancreas), even with EUS, laparoscopy, and ultrasound. Apart from insulino-
mas, these tumours are usually malignant (Oberg et al ., 2003 ) ( Table 1.8 ).
The extra pancreatic site is more common and often a problem with gastri-
nomas (Jensen, 2004 ). It is not unknown for the primary not to be found. Any
strategy must take these factors into account and the surgeon must remember
that histological examination can never reliably predict benign or malignant
behaviour in endocrine tumours. Surgical approaches include local resection
and total pancreatectomy in MEN patients.
Enucleation has been suggested but we do not favour this approach. It is
associated with a significant incidence of pancreatic leaks and is illogical for a
group of tumours in which the majority are malignant (Ruiz-Tovar et al .,
2008 ) (Table 1.9).
Irrespective of the mode of presentation we believe all these patients should
be offered surgery if they are fit enough and disseminated disease has been
excluded (see Fig. 1.37 ).
CT scanning, laparoscopy, and intraoperative ultrasound are essential, but if
the primary tumour is confidently located, and there is no evidence of disease
elsewhere, resection is undertaken. With an insulinoma, the lesion may be
small and we have found selective venous sampling valuable in patients where
imaging fails to locate the tumours. In MEN patients, the tumours are always
PANCREAS
56
multiple and often of varying sizes. Even intraoperative ultrasound may fail to
detect all these lesions and, if multiple tumours are demonstrated, a total pan-
createctomy should be performed. The presence of tumour dissemination, and
particularly liver metastases, is a contraindication to surgery in almost every
case. Rarely, patients present with small numbers of functioning liver lesions
after an apparently curative resection of a primary tumour. They may be
potential surgical candidates, particularly if symptoms cannot be controlled.
However, chemotherapy must always be employed initially in these patients as
the usual outcome is the rapid appearance of a much larger numbers of lesions
and frequently extrahepatic disease.
Pancreatic adenocarcinoma
The pancreas is the site for a number of exocrine tumours of varying malig-
nant potential (see Table 1.10 ). Many of these have come to prominence only
recently but the better understanding of the pathology and natural history is
vital when deciding the most appropriate management. The range includes
Table 1.9 Presentation, sites, and malignant potential of gastroenteropancreatic
neuroendocrine tumours (GEP–NETs) (Ruiz-Tovar et al ., 2008 )
Tumour Frequency Location % Malignancy % Syndrome
Insulinoma 70–75% Pancreas > 99 < 10 Hypoglycaemia
weight gain
Gastrinoma 20–25% Duodenum 70
Pancreas 25
> 50 Pain, diarrhoea,
ulceration
VIPoma 3–5% Pancreas 90 > 50 WHHA, acidosis,
flushing
Glucagonoma 1–2% Pancreas 100 > 70 NME, diabetes,
cachexia, weight
loss
Somatostatinoma < 1% Pancreas 55
Duod/jejunum 45
> 50 Steatorrhoea,
diabetes,
gallstones,
weight loss
PPoma < 1% Pancreas 100 > 60 Pain, weight loss,
diarrhoea
Bombesinoma < 1% Pancreas 100 ? —
Non-functioning < 15 Pancreas and GI
tract
> 80 Mechanical
problems,
tumour bulk
NME, necrolytic migratory erythema, tbc; WDHA, watery diarrhoea, hypokalaemia, achlorhydria, tbc.
PANCREATITIS
57
cystic lesions, mucinous lesions with dysplasia, pancreatic adenocarcinoma,
and a number of ductal lesions that often make the clinical management com-
plex. Principal amongst these are the proliferative ductal lesions that have been
thought to be the forerunner of ductal adenocarcinoma since the 1950s. These
lesions are graded according to their architectural complexity (Pan1NA,
Pan1NB, and, if there is substantial pseudostratification, Pan1N2) and they are
not infrequently found at the resection margin following pancreaticoduo-
denectomy. There is not sufficient evidence about the progression of these
lesions to recommend routine progression to a completion pancreatectomy
and we observe these patients carefully during their postoperative tumour
surveillance.
Pancreatic adenocarcinoma is aggressive and associated with a very poor
outlook (Office for National Statistics, 2005 ). The incidence appears to have
increased steadily over the last 50 years and in the USA now it represents the
fourth most common solid organ malignancy (Ghadirian et al ., 2003 ; Henson
et al ., 2009 ). Despite all the clinical and basic research that has been conducted,
we know little more about the aetiology and our management still has had lit-
tle impact on the outcome. Even an aggressive surgical approach in countries
where screening facilities are freely available has not altered the results signifi-
cantly (Hines and Reber, 2008 ).
Other problems occur when trying to examine surgical results due to the use
of Whipple’s operation as the yardstick by which many pancreatic units feel
they are judged. Despite the evidence that these tumours metastasize early, and
are then incurable, many series contain significant numbers of patients who
are node positive, have involved resection margins, or who have had excision
of large tumours (Takao et al ., 2008 ).
Our belief is that patients should only be subjected to resection surgery for
adenocarcinoma after a diligent search (both preoperatively and intraopera-
tively) for extra pancreatic disease and in tumours where there is a genuine
chance of a cure. With respect to this, size is an important consideration and
Table 1.10 Pancreatic epithelial tumours and their malignant potential
Benign Borderline Malignant
Serous cystadenoma
Mucinous cystadenoma
Intraduct papillary
mucinous adenoma
Mature teratoma
Mucinous cyst with moderate
dysplasia
Intraduct papillary mucinous
tumour with moderate
dysplasia
Solid pseudopapillary tumour
Severe duct dysplasia
Ductal adenocarcinoma
Cysadenocarcinoma
Ductal lesions (Pan1N)
Miscellaneous rare lesions
PANCREAS
58
we believe that the upper limit should be 3.5cm. Local invasion is more con-
troversial and even small tumours, if very posterior, can invade the portal vein
or SMA. If the tumour is less than 3.5cm in size but involves either the portal
vein or SMA then local resection with the necessary vascular resection and
reconstruction should be considered (Matsuno et al ., 2001 ; Tseng et al . 2006 ).
However, involvement of both vessels is a contraindication to surgery imply-
ing either extra pancreatic infiltration (rather than direct involvement) or a
tumour larger than appropriate for resection.
Preoperative assessment of patients who present with sinister symptoms or a
diagnosis based on initial findings must be exhaustively investigated ( Fig. 1.38 ).
This should aim to exclude extrapancreatic disease and identify vascular
involvement that would preclude a curative resection.
Many of these patients are jaundiced at presentation but we prefer to avoid
placing a biliary stent particularly at ERCP. Endoscopic stenting increases the
morbidity and mortality of the procedure and can make assessment of the
extent of the disease very difficult (Sewnath et al ., 2001 ; Bhati et al ., 2007 ).
Intraoperative assessment is less clear, particularly in patients that have lower
common bile cholangiocarcinomas if there is fibrosis of the duct secondary to
a stent and multiple frozen sections are required to confidently identify an
adequate clearance margin. If the bilirubin is very high, or the patient is devel-
oping complications such as renal impairment, we prefer percutaneous biliary
drainage but find that this is rarely necessary if patients can be assessed and
offered surgery rapidly (Povoski et al ., 1999 ; Nimura, 2008 ). Even in patients
whose bilirubin is more than 300µmol/L, recovery after resection or bypass is
much smoother if drainage has been avoided. Once a pancreatic mass is con-
firmed then further investigations specifically address the issue of operability
(with curative intent) although the final decision is frequently not made until
laparotomy (see Fig. 1.39 ).
Preoperative workup consists of CT scanning, CEA and CA 19-9 estimation,
and laparoscopy with intraoperative ultrasound. We do not perform laparos-
copy with the aim of proceeding immediately to surgery but as described ear-
lier use the procedures to assess suitability for surgery and frequently we will
biopsy what we believe are benign liver lesions (hamartomas and fibrous areas)
or peritoneal nodules but need to confirm this with paraffin sections. Prior to
any surgical procedure in jaundiced patients we will always give a minimum of
48 hours and preferably 72 hours of oral bile salts (ursodeoxycholic acid,
200mg twice a day), parenteral vitamin K 10mg twice a day, and intravenous
fluids. Despite this, the anaesthetists always find that the patients remain
‘dry’ but with this regimen postoperative renal problems are exceptionally
uncommon.
PANCREATITIS
59
Fig. 1.38 Investigation of a suspected pancreatic mass.
Pancreate mass
metastatic
disease
Pancreate mass
no extra hepatic
disease
Biopsy
Laparoscopy +
IOUS
Dilated CBD
normal PD
Dilated CBD
DilatedPD
Laparotomy for
presumed
pancreatic
carcinoma
Consider ERCP
if suspected
ampullary lesion
EUS
laparoscopy +
IOUS
Weight loss
pain (back)
jaundice
Ultrasound Dilated CBD
Mass with no
duct dilatation
CT, MRI, CA19.9
No pancreatic
mass
PANCREAS
60
Fig. 1.39 Treatment of a proven pancreatic mass.
External
drainage
Potentially
operable
>20x Normal
<20x Normal
Technically
inoperable on
imaging
Jaundiced
Metastatic
disease
Non-jaundiced
Pancreatic
mass
• Laparoscopy
• Ultrasound
• Biopsies
No
extrapancreatic
disease
Extrapancreatic
disease
Chemotherapy
Adeno
carcionema
Operate
Inoperable
Biliary bypass
Whipple’s
• Exploration
• US
• Biopsies
PANCREATITIS
61
The preoperative discussion with the patients should be frank and honest
and the findings are explained to them. The options that are discussed do
partly depend on the symptoms and particularly evidence of gastric outlet
obstruction (see Fig. 1.40 ):
♦
Stenting alone in the case of inoperable disease
♦
Stenting and gastroenterostomy in unfi t patients with inoperable disease
but gastric outlet syndrome
♦
Biliary bypass for incurable disease
♦
Whipple’s procedure for potentially curable tumours.
Stenting alone or stenting and gastroenterostomy are reserved for patients
who are not fit for major biliary surgery as we believe that the outcome from
biliary bypass is superior to stenting alone. Many patients with tumours (par-
ticularly if large) in the pancreatic head will have gastric outlet obstruction and
these patients lose weight principally due to the mechanical problem. Failure
to address this results in continued weight loss and an inability to tolerate
chemotherapy regimens. These patients deteriorate more rapidly as a conse-
quence and the deterioration is blamed solely on the tumour and paraneoplas-
tic effects. In patients who have a successful biliary (or gastrobiliary) bypass,
weight is maintained longer, quality of life is better, and hospital admissions
Fig. 1.40 Management of a proven pancreatic adenocarcinoma.
Investigate
generally
inoperable
Chemotherapy
palliative
treatment
Symptomatic
Pancreatic
adenocarcinoma
Jaundice
Billirubin <20x
normal
Billirubin >20x
normal
Incidental
mass
Investigate
and biopsy
Resectable
External drain
Surgery
Chemotherapy
Non-resectable
Investigate
Operable
Inoperable
Bypass
Pancreatic surgery/resection
(pancreaticoduodenectomy)
Surgery
Size
local invasion
dissemination
Weight loss
and pain
Gastric outlet
obstruction
PANCREAS
62
are reduced. We believe this allows patients to tolerate their chemotherapy and
the combination results in an improved survival.
This philosophy means that we feel comfortable exploring borderline
patients (such as those whose tumours are at the upper limit in terms of size
criteria but not where dissemination is proven) and if the intraoperative find-
ings preclude a curative resection, then we perform a biliary bypass.
Determining operability ( Figs. 1.41 – 1.45 ) A transverse incision is used and a
thorough laparotomy performed. Frozen sections are always booked and are
used at the beginning and end of the procedure. The early sections are for suspi-
cious nodules/nodes and the final sections for the resection margin (pancreas in
Whipple’s, bile duct in cholangiocarcinomas). We use frozen sections to sample:
♦
Any suspicious peritoneal or serosal nodule
♦
Any liver lesion
♦
Hepatoduodenal ligament lymph nodes
♦
Retropancreatic nodes after Kocherizing the duodenum
♦
The pancreatic mass.
Fig. 1.41 A thorough laparotomy may reveal peritoneal disease or evidence of direct
invasion into neighbouring structures such as the small bowel mesentery.