Gastrectomy for adenocarcinoma

Louise Powell MB ChB FRCA

Gill Hood FRCA Key points
Andrew Wyman MD FRCS The overall incidence of
gastric carcinoma has
decreased over the past
two decades. There are
fewer distal gastric
adenocarcinomas but more
Over the last two decades, there has been a protection layer of mucus. Normal gastric juice proximal carcinomas
gradual decline in the number of patients pre- pH is 1.0; this acidic environment is usually affecting the gastro-
oesophageal junction.
senting with gastric adenocarcinoma. In 2005, bactericidal and also required for pepsinogens
the overall incidence was 9.4 cases per 100 000 to work effectively.4 Accurate staging is essential
population within the UK and 6.4 per 100 000 The muscle wall of the stomach contains to determine the most
within Europe;1,2 its incidence in men is twice three types of fibre: superficial longitudinal appropriate therapeutic
management.
of that of women. In the UK, there are about fibres (mostly concentrated along the lesser and
8200 new cases each year and 6000 deaths.2 greater curvatures), circular fibres ( prominent Anaesthetic technique
The decrease in incidence is possibly due to a in the body plus forming the pyloric sphincter), includes an epidural and
reduction in the number of smokers, treatment and innermost oblique fibres. The pyloric general anaesthesia, with a
potential for invasive
of Helicobacter pylori, and a healthier diet sphincter is both anatomical and physiological,
monitoring and
(more fresh fruit and vegetables).3 Also, there but it has only a limited role in the control of
postoperative high
has been a change in distribution, with an gastric emptying. The antrum, pylorus, and dependency care depending
increase in the incidence of carcinomas in the upper duodenum function as a unit. Contraction on co-morbidity and type of
lower third of the oesophagus and gastro- of the antrum is followed by contraction of the surgery.
oesophageal junction, and a decrease in distal pylorus and duodenum, so that the muscular
Perioperative chemotherapy
malignancy. This has resulted in the need contraction prevents solids advancing and only improves long-term survival,
for more total compared with subtotal small volumes of gastric contents enter the but potential adverse effects
gastrectomies. duodenum at a time. In addition, osmoreceptors must be sought before
in the duodenum sense hyperosmolality which gastrectomy.
leads to a decrease in gastric emptying.4
Anatomy and physiology Pancreatic enzyme secretion is enhanced by
Louise Powell MB ChB FRCA
cephalic vagal stimulation and the presence of
Before discussion of the pathology and treat- SPR Anaesthetics
food in the antrum and duodenum. This func- Sheffield Teaching Hospitals NHS Trust
ment of gastric carcinoma, it is important to
tion is lost with both a subtotal and a total gas- Royal Hallamshire Hospital
appreciate the normal anatomy and physiology. Glossop Road
trectomy along with the production of intrinsic
A summary of the functions of the stomach is Sheffield S10 2JF
factor, essential for vitamin B12 absorption. UK
seen in Table 1. The gastro-oesophageal
Hence, after gastrectomy, there is no control
sphincter is a physiological entity, with closure Gill Hood FRCA
over the rate at which food enters the duode-
under vagal control. The smooth muscle Consultant Anaesthetist
num and jejunum; this can lead to dumping,
relaxes with peristalsis, enabling food to enter Sheffield Teaching Hospitals NHS Trust
whereby fluid shifts into the gastrointestinal Northern General Hospital
the stomach. After this, tonic contraction pre- Herries Road
tract giving symptoms of hypovolaemia.
vents oesophageal reflux. This function is Sheffield S5 7AU
The blood supply is provided by five differ-
obviously lost after a total gastrectomy. UK
ent anastomosing arteries derived from Tel: 44 (0)114 2434343
Parietal cells (hydrochloric acid and intrin- Fax: 44 (0)114 2268736
branches of the coeliac artery. The lymph drai-
sic factor secretion) and chief cells ( pepsino- E-mail: gillian.hood@sth.nhs.uk
nage from the mucosa and submucosa are in
gens secretion) are found within the fundus and (for correspondence)
continuity, draining into lymph nodes which
body of the stomach. Stimulation of the parietal Andrew Wyman MD FRCS
follow the arterial supply. From the perigastric
cell by histamine H2 receptors, gastrin, and Consultant Surgeon
nodes, lymph drains into the splenic, hepatic,
acetyl choline via M1 muscarinic receptors Sheffield Teaching Hospitals NHS Trust
and coeliac nodes. Owing to the anatomical Royal Hallamshire Hospital
( parasympathetic nervous system) promotes
arrangement, it is possible for malignant cells Glossop Road
acid secretion. Glands in the cardia and pylorus Sheffield S10 2JF
to migrate away from the primary site.5
are responsible for secreting the mucosal UK
doi:10.1093/bjaceaccp/mkp007 Advance Access publication 4 March, 2009
Continuing Education in Anaesthesia, Critical Care & Pain | Volume 9 Number 2 2009 65
& The Author [2009]. Published by Oxford University Press on behalf of The Board of Directors of the British Journal of
Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournal.org
Gastrectomy for adenocarcinoma

Table 1 Functions of the stomach recent onset dyspepsia alone. Persistent is defined as the continu-
Functions ation of specified symptoms, signs, or both beyond that which
would normally be associated with self-limiting problems.6
Storage of food Consequently, the patient may have symptoms for 46 weeks
Breakdown of solids into chyme after mixing with gastric secretions
Controlled release of chyme into small intestine, aiding efficient digestion and
before referral. After endoscopy and biopsy, histopathology con-
absorption firms the diagnosis of gastric adenocarcinoma.
Defence: acidity kills bacteria
Secretion: intrinsic factor, pepsinogens

The parasympathetic nerve supply is derived from the vagal
nerve and sympathetic from the coeliac plexus. Parasympathetic
stimulation promotes acid secretion, closure of the gastro-
oesophageal sphincter, and gastric motility, whereas sympathetic
stimulation delays gastric emptying.
Risk factors
More than 80% of gastric cancer arises in patients more than 65 yr
of age. There are a number of risk factors associated with gastric
malignancies including:
(i) genetic, e.g. E-cadherin (CDH1) gene mutations (an epi-
thelial adhesion molecule) associated with a diffuse linitis
plastica adenocarcinoma with a poor prognosis;
(ii) smoking;
(iii) Helicobacter pylori infection;
(iv) previous gastric surgery;
(v) pernicious anaemia;
(vi) atrophic gastritis;
(vii) poor socioeconomic status.
Staging
Early gastric cancer is that confined to the mucosa or mucosa and
submucosa, irrespective of lymph node involvement, whereas
advanced gastric cancer extends into the muscularis propria or
beyond. In the UK, around 10% of cases are early gastric cancer
at diagnosis.7 Staging determines the degree of spread of the
gastric tumour, usually classified by the Tumour, Nodes,
Metastasis (TNM) classification system (Tables 2 and 3).
Accurate staging is extremely important to guide appropriate
management planning. Given the morbidity and mortality of
gastric surgery, only those with potentially curable disease should
undergo a gastrectomy. All patients with a diagnosis of gastric ade-
nocarcinoma should have a computed tomography scan (CT) and a
laparoscopy. Some centres also use endoscopic ultrasound (EUS);
this is useful in the assessment of early gastric adenocarcinoma as,
unlike CT, it can distinguish between T1 and T2, but it is not able
to distinguish T2 from T3 lesions.8 EUS is less effective in asses-
sing tumours in the cardia compared with other areas of the
stomach. It can also be used for N staging, but not M staging, pro-
viding a complementary investigation to CT. Spiral contrast
enhanced CT with 5 mm collimation is the optimal scan. Tumours

Table 2 TNM staging system

Classification Invasion of
Presentation and diagnosis
Symptoms are a poor predictor of pathology. Most patients within Tumour
T1 Lamina propria T1a, submucosa T1b
the UK (90%) will have advanced gastric malignancy at presen- T2 Muscularis propria, subserosa
tation. As a result, guidelines have been implemented to increase T3 Penetrates serosa
awareness of patients at risk and promote early referral. The T4 Adjacent structures
Lymph nodes
National Institute for Health and Clinical Excellence (NICE) N0 No lymphnode metastasis
guidelines for suspected cancer state that a patient of any age pre- N1 Regional nodes 16 nodes
senting with dyspepsia and alarm symptoms should have an N2 715 nodes
N3 .15 nodes
urgent referral for endoscopy.6 An urgent referral means that the Metastases
patient should be seen within 2 weeks. Alarm symptoms include: M0 No distant metastases
chronic gastrointestinal bleeding; dysphagia; progressive uninten- M1 Distant metastasis

tional weight loss; persistent vomiting; iron deficiency; anaemia;

epigastric mass; and a suspicious barium meal result. NICE also
recommend that any patient presenting with the following have an Table 3 TNM staging classification. Any N3 or M1stage IV disease
urgent referral to an upper gastrointestinal specialist: unexplained
T/N N0 N1 N2
upper abdominal pain and weight loss, with or without back pain;
upper abdominal mass without dyspepsia; and obstructive jaundice T1 Ia Ib II
(consider urgent ultrasound if available). T2 Ib II IIIa
T3 II IIIa IIIb
If the patient is aged 55 yr or older, they should be referred for T4 IIIa IV IV
urgent endoscopy if presenting with unexplained and persistent

66 Continuing Education in Anaesthesia, Critical Care & Pain j Volume 9 Number 2 2009

are best demonstrated after gastric distension with 600800 ml of
water, which can be difficult to achieve in a patient with advanced
gastric carcinoma. CT is said to identify 80 88% of patients with
advanced disease and has a role in T, N and M staging. Metastases
(75 80%) will be identified with CT, but peritoneal disease can be
difficult to detect.3
Guidelines from the British Society of Gastroenterology state
that laparoscopy should be a routine investigation before radical
resection. Previous studies have shown that up to one-third of
patients have more advanced disease than anticipated.8 It allows
accurate detection of peritoneal spread, nodal involvement, and
distant metastases.
Management options
Once a patient has been diagnosed with a potentially curable
(stages I III) gastric adenocarcinoma, they should proceed to have
perioperative chemotherapy and a gastrectomy with lymph node
clearance.
Adjuvant chemotherapy
Until recently, gastrectomy alone was considered the optimal treat-
ment for gastric carcinoma, with adjuvant chemotherapy reserved
for those who had incurable locally advanced or metastatic
disease. The results of the MAGIC (MRC Adjuvant Gastric
Infusional Chemotherapy) trial have changed this. Patients were
randomized to receive either surgery alone or perioperative che-
motherapy and surgery. The chemotherapy involved three preo-
perative and three postoperative cycles of epirubicin, cisplatin, and
fluorouracil (ECF). The primary endpoint was overall survival. The
5 yr survival rate was 36% and 23% for the perioperative che-
motherapy group and the surgery group, respectively.9
Given this evidence, perioperative chemotherapy is now an
essential adjuvant treatment. ECF has an acceptable side-effect
profile, but is not without risk. Anaesthetists need to be aware of
these, given that most patients will have received chemotherapy
before their major surgery. Epirubicin is known to cause cardiac
toxicity, particularly when given above doses of 200 mg m22
(impaired systolic LV function).10 The MAGIC trial dose of epiru-
bicin administered was 50 mg m22. In addition, patients were
excluded from the study if they had unstable ischaemic heart
disease, and epirubicin was omitted if the left ventricular ejection
fraction was ,50% (assessed by multigated acquisition scanning
or echocardiography before starting chemotherapy). Cisplatin is
known to cause nephrotoxicity; consequently, patients were
excluded if their creatinine clearance was ,60 ml min21. Before
each cycle of chemotherapy, blood was obtained to measure full
blood count, renal, and liver function. The cisplatin dose was
modified according to repeated measures of creatinine clearance.
Nearly every patient given ECF chemotherapy suffers haematologi-
cal side-effects; thrombocytopenia is the most common.
Continuing Education in Anaesthesia, Critical Care & Pain j Volume 9 Number 2 2009
Gastrectomy for adenocarcinoma
The gastrectomy should be 36 weeks after the completion of
the third cycle of chemotherapy. The three postoperative che-
motherapy cycles commence 6 12 weeks after surgery.
Surgery
The surgical options include a subtotal or total gastrectomy, with
first and second compartment lymph node clearance. The deciding
factor is the location of the tumour. In the literature, the accepted
distance from the proximal edge of the tumour to the cardia which
would dictate a subtotal gastrectomy varies from 3 to 6 cm. The
British Society of Gastroenterology guidelines recommend that any
proximal tumour within 5 cm of the cardia requires a total gastrect-
omy; beyond that a subtotal gastrectomy is considered appropriate.
The latter is associated with a better nutritional status and quality
of life.
After a gastrectomy a roux-en-Y reconstruction establishes con-
tinuity of the gastrointestinal tract. The stomach remnants (subtotal
gastrectomy) or oesophagus (total gastrectomy) undergo a side
anastomosis to the proximal jejunum. The proximal duodenum
forms a blind end and the distal duodenum is re-anastomosed 50
60 cm along the jejunum to prevent bile reflux. Previously, a
radical gastrectomy involved a total gastrectomy, lymphadenect-
omy, splenectomy, and excision of the distal pancreas. This pro-
cedure carried significant morbidity and mortality. Current
guidelines state that the distal pancreas should not be removed
unless there is direct invasion and is a potentially curative pro-
cedure. A splenectomy has an adverse effect on prognosis and is
not recommended for tumours in the distal two-thirds of the
stomach. Splenectomy and splenic hilar node resection should only
be considered for those with proximal tumours along the greater
curvature or posterior wall where splenic node involvement is
likely.3
Lymphadenectomy
There has been considerable controversy over the years regarding
the extent of lymphadenopathy. D1 resection involves removal of
the perigastric lymph nodes and a D2 resection includes perigas-
tric, coeliac, hepatic, and splenic nodes. Studies from specialist
centres suggest a survival benefit from a D2 lymphadenectomy;11
hence, this is the current recommendation.
Specialist oesophago-gastric cancer teams
Data support better outcomes in hospitals treating large numbers of
patients with gastric cancer. As a result, guidance on cancer ser-
vices advises that there should be regional specialist oesophageal
gastric cancer teams which serve a catchment population of at least
one million patients.12 These recommendations are gradually being
implemented nationally.
67
Gastrectomy for adenocarcinoma
Anaesthetic management
Preoperative assessment
The patients preoperative pathophysical state is a key factor affect-
ing outcome. The staging laparoscopy will also indicate if there
were any problems tolerating a short, but potentially cardiorespira-
tory compromising, procedure.
History and examination
Many patients are smokers and are likely to have multiple
co-morbidities such as ischaemic heart disease, hypertension, and
respiratory pathology. These are associated with increased perio-
perative morbidity, especially if poorly controlled. Smokers should
be strongly advised to stop before surgery. A nutritional assess-
ment is necessary. Ask about symptoms including reflux, nausea,
vomiting, and dysphagia. Determine of amount of weight loss over
a time period and enquire about types and volume of food the
patient is able to ingest. Malnourished patients suffer more post-
operative complications. The risk increases with a body mass
index of ,18.5, 20% weight loss, body weight of ,90% of pre-
dicted, and hypoalbuminaemia.3 Obesity is also associated with
adverse events. After the MAGIC trial, providing there were no
contraindications, most patients will have received preoperative
chemotherapy, with the possibility of haematological, renal, and
cardiac compromise.
Investigations
Routine investigations include baseline haematological and bio-
chemical investigations including a cross-match, resting electrocar-
diogram (ECG), pulmonary function tests, and a chest X-ray. If the
FEV1 is reduced by 20% or more, pulmonary complications are
more likely. Patients with cardiorespiratory disease will also need
evaluation of their pathology and reserve by means of an echocar-
diogram (may have been done before chemotherapy), exercise
ECG, cardiopulmonary exercise testing, or shuttle test. Patients
who are unable to complete 350 m of a shuttle test are at increased
risk of mortality.13
Preoperative preparation
Patients with co-existing disease need optimizing, with treatment
of any acute or unstable medical conditions before surgery.
Surgery on any patient with post-chemotherapy neutropenia is
usually postponed for 3 weeks and the patient is then reassessed.
Dietetic advice should be given to malnourished patients.
Preoperative counselling from the surgical team is necessary as the
individual will experience a significant change in their quality of
life; more so for a total, than subtotal, gastrectomy.
Thromboprophylaxis should consist of low molecular weight
heparin and antithromboembolic stockings the evening before
surgery, plus calf compression intraoperatively.
68 Continuing Education in Anaesthesia, Critical Care & Pain j Volume 9 Number 2 2009
Appropriate postoperative care depends on the extent of the
surgery and co-morbidities. All but the fittest of patients should be
managed on a high dependency or postoperative surgical unit.
Intraoperative management
An effective thoracic epidural is still the gold standard for analge-
sia for upper gastrointestinal surgery. Several trials have demon-
strated that epidural analgesia provides superior analgesia
compared with opioid-based patient-controlled infusions, also
reducing the incidence of postoperative cardio-respiratory and
thromboembolic complications. A large randomized, non-blinded
study comparing epidural with opioid analgesia for high-risk
patients having upper gastrointestinal surgery (the MASTER trial;
Multicentre Australian Study of Epidural Anaesthesia) reported no
difference in overall mortality or major morbidity between the
groups. However, pain scores and incidence of postoperative res-
piratory failure were significantly lower in the epidural group.14
All patients will require large bore i.v. access. Those having
extensive surgery with co-morbidities will also need invasive
monitoring with arterial and central venous lines, before or after
induction depending on the state of the patient. All patients have
the potential for aspiration of stomach contents; hence, a rapid
sequence induction is necessary. Perioperative antibiotics should
be given according to local guidelines.
Postoperative nutritional management
There is a lack of evidence and guidance on optimal management
of nutritional status. Within our centre, if a patient is malnourished
before operation, they have a feeding jejunostomy sited and
feeding commenced on day 1 after operation. Otherwise, patients
with a straightforward postoperative course are nil by mouth until
commencement of oral intake by day 5.
Complications
As with any major surgical procedure, there is potential for cardio-
vascular and respiratory complications. Surgical complications
include anastomotic leaks and intra-abdominal abscesses.
Guidelines suggest that centres should be achieving more than
30% curative surgery rates, with an in-hospital mortality of
,10%.3
All patients have nutritional sequelae and, for the majority, it
affects their quality of life significantly, particularly after a total
gastrectomy. Most patients lose weight for a variety of reasons.
Patients do not experience normal hunger and have early satiety; in
addition, they often experience the early, late, or both dumping
syndromes. Meals need to be small and frequent. There is a
reduction in pancreatic enzyme secretion causing malabsorption of
carbohydrates and lipids leading to bloating and steatorrhoea.
Many patients become anaemic as iron needs an acidic environ-
ment to be absorbed in the ferrous (Fe2) state. B12 supplemen-
tation is necessary.

Prognosis
Prognosis depends on the stage of malignancy. Overall, the UK
5 yr survival rates are 15% for men and 18% for women.
Although this is still poor, the percentage surviving has increased
over recent years and will continue to do so with advances in diag-
nosis and treatment.
References
1. Office for National Statistics. Cancer Statistics Registrations: Registrations of
Cancer Diagnosed in 2004, England. Series MB1 No. 34. London: National
Statistics, 2007
2. CRC (Cancer Research Campaign). Cancer Stats IncidenceUK. London:
Cancer Research Campaign, 2007
3. Allum WH, Griffin SM, Watson A, Colin-Jones D. Guidelines for the
management of oesophageal and gastric cancer. Gut 2002; 50: 1 23
4. Ganong W. Regulation of gastric function. Review of Medical Physiology,
16th Edn. East Norwalk, CT: Appleton and Lange, 1993; 446 52
5. Snell RS. The abdominal cavity. Clinical Anatomy for Medical Students, 5th
Edn. London: Little Brown and Company, 1995; 195 9
Continuing Education in Anaesthesia, Critical Care & Pain j Volume 9 Number 2 2009
Gastrectomy for adenocarcinoma
6. NICE Clinical Guideline no. 27: Referral Guidelines for Suspected Cancer. June
2005. Available from www.nice.org.uk/CG027NICEguideline
7. Sayegh ME, Wyman A. Gastric carcinoma. Surgery 2002; 20: 236 40
8. Hohenberger P, Gretschel S. Gastric cancer. Lancet 2003; 362: 305 15
(review)
9. Cunningham D, Allum WH, Stenning SP et al., MAGIC Trial Participants.
Perioperative chemotherapy versus surgery alone for resectable gastroe-
sophageal cancer. N Engl J Med 2006; 355: 11 20
10. Mercuro G, Cadeddu C, Piras A et al. Early epirubicin-induced myocar-
dial dysfunction revealed by serial tissue Doppler echocardiography:
correlation with inflammatory and oxidative stress markers. Oncologist
2007; 12: 1124 33
11. McCulloch P, Niita ME, Kazi H, Gama-Rodrigues JJ. Gastrectomy with
extended lymphadenectomy for primary treatment of gastric cancer. Br
J Surg 2005; 92: 513 (review)
12. Improving Outcomes in Upper Gastro-intestinal Cancers. Guidance on
Commissioning Cancer Services. NHS Executive, January 2001
13. Murray P, Whiting P, Hutchinson SP, Ackroyd R, Stoddard CJ, Billings C.
Preoperative shuttle walking testing and outcome after oesophagogas-
trectomy. Br J Anaesth 2007; 99: 809 11
14. Low J, Johnston N, Morris C. Editorial; epidural analgesia: first do no
harm. Anaesthesia 2008; 63: 1 3
Please see multiple choice questions 22 25
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