Guidelines for the Management of Oesophageal and Gastric Cancer

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doi:10.1136/gut.50.90005.v1

2002;50;1-23Gut

W H Allum, S M Griffin, A Watson and D Colin-Jones

gastric cancerGuidelines for the management of oesophageal and

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Oesophageal cancer may be inuenced by a reduction in theduration and severity of gastro-oesophageal reux and by areduction in the incidence of obesity (grade C).

Eradication of Helicobacter may decrease gastric cancer inci-dence (grade C).

Diagnosis The index of suspicion for cancer is high when vague

dyspeptic symptoms are combined with alarm symptoms(for example, weight loss, vomiting, and anaemia). Generalpractitioners should be encouraged to refer patients as earlyas possible (grade B).

Rapid access gastroscopy is the investigation of choice withappropriate biopsy for those with risk symptoms (grade C).

Patients with a longstanding history of reux and/ordysphagia should not be assumed to be suffering frombenign stricture or simple oesophagitis until endoscopy andbiopsy has been performed (grade C).

High grade dysplasia of the oesophagus should precipitateurgentrepeat endoscopy and biopsy as a signicant numberof patients will already have or develop intramucosal cancer(grade B).

Antisecretory therapy should be ideally withheld until afterendoscopy to avoid misdiagnosis (grade B).

The diagnosis of gastric cancer should be suspected in allpatients with recent onset dyspepsia over the age of 50 years (grade C).

Gastric ulcers should be followed up to healing with repeatbiopsy (grade B).

Staging Staging needs to be thorough and accurate for all patients

in order to plan optimal therapeutic options (grade B). Accurate staging is achieved by a combination of tech-

niques interpreted by dedicated staff in a timely fashion(grade B).

Initial staging assessment should include spiral computedtomography (CT) of the thorax and abdomen to determinethe presence or absence of metastatic disease (grade B).

In the absence of metastatic disease, assessment of operability is preferably made by endoscopic ultrasound(grade B).

Adjuncts to staging include magnetic resonance imaging(MRI), bronchoscopy, laparoscopy, and transabdominalultrasound (grade B).

Pathology Diagnosis of high grade dysplasia both in Barretts oesoph-

agus and in the stomach should be made by an experiencedhistopathologist and corroborated by a pathologist with aspecial interest in gastrointestinal disease (grade C).

Reports on oesophageal resection specimens should in-clude, as a minimum, type of tumour, depth of invasion,involvement of the resection margins, vascular invasion, thepresence of Barretts metaplasia, and the number of nodesresected and the number containing metastatic tumour

(grade B). Reports on gastric resection specimens should include, as aminimum, type of tumour, depth of invasion, involvementof the resection margins, nodal disease (including numberof involved lymph nodes), and metastatic spread (grade B).

Oesophagogastric junctional tumours should be classiedas type I (distal oesophageal), type II (cardia), and type III(proximal stomach) (grade C).

Treatment Treatment and management of all patients should be

undertaken in the context of a multidisciplinary team which plans and performs staging, treatment selection(radical and palliative), treatment provision, post-treatmentcare, and follow up (grade C).

Careful evaluation of the patients pretreatment healthmust be made, particular attention being paid to thecardiovascular and respiratory systems and performancestatus (grade C).

Preoperative assessment Routine investigations should include haematological and

biochemical proles (grade C), a resting ECG (grade B),chest x ray (grade B), pulmonary function tests (grade B),and exercise testing (grade C).

Optimising the patients tness for surgery is a multidisci-plinary process and all available expertise should be utilised(grade C).

Patients should be encouraged to stop smoking immedi-ately (grade C).

All patients should have antithrombotic (grade A) andantibioticprophylaxis (gradeC) instituted at an appropriatetime in relation to their surgery and postoperative recovery.

Anaesthesia for oesophageal surgery should only beconducted by anaesthetists familiar with one lung ventila-tion and epidural analgesia (grade C).

Quality of life at presentation should be assessed and takeninto consideration in treatment planning (grade B).

Treatment: oesophageal resection Oesophagectomy should be undertaken only in centres

capable of carrying out careful case selection, with a largecase volume and sufcient surgical and intensive careexperience (grade B).

There is no evidence favouring one method of oesophagealresection over another (grade C).

The operative strategy should ensure that adequatelongitudinal and radial resection margins are achieved whenever possible, along with a lymphadenectomy appro-priate to the histological tumour type and its location(grade B).

Single layer manual or stapled anastomoses can be used(grade B).

Clinical anastomotic leakage should not exceed 5% (gradeB).

Curative (R0) resection rates should exceed 30% (grade B). Overall hospital mortality for oesophageal resection should

be less than 10% (grade B).

Treatment: gastric resection The best results are likely to be produced by experienced

surgeons operating in specialised units as part of a

multidisciplinary team (grade B). Distal (antral) tumours should be treated by subtotal gast-rectomy and proximal tumours by total gastrectomy (gradeB).

Limited gastric resections should presently only be used forpalliation or in the very elderly (grade B).

Patients with curable cancers of the stomach shouldundergo a D2 lymphadenectomy (grade B).

The extent of lymphadenectomy should be tailored to theage and tness of the patient together with the location andstage of the cancer (grade C).

The distal pancreas and spleen should not be removed aspart of a resection for a cancer in the distal two thirds of thestomach (grade A).

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Abbreviations: CT, computed tomography; MRI, magnetic resonanceimaging; 5-FU, 5-fluorouracil; ECF, epirubicin, cisplatin, and 5-FU;FAMTX, 5-FU, adriamycin, and methotrexate; PDT, photodynamictherapy; APC, argon plasma coagulation; ACA, adenocarcinoma; SCC,squamous cell carcinoma; EUS, endoscopic ultrasound; ASA, AmericanSociety of Anesthesiologists.

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The distal pancreas should be removed only when there isdirect invasion and still a chance of a curative procedure inpatients with carcinoma of the proximal stomach (grade A).

Resection of the spleen and splenic hilar nodes should onlybe considered in patients with tumours of the proximalstomach located on the greater curvature/posterior wall of the stomach close to the splenic hilum where the incidenceof splenic hilar nodal involvement is likely to be high (gradeC).

Curative (R0) resection rates should exceed 30% (grade B). Inhospital mortality should be less than 10% for total gast-rectomy and less than 5% for subtotal/partial gastrectomy(grade B).

Treatment: chemotherapy and radiotherapy Oesophageal cancer There is no evidence for a role of adjuvant chemotherapy in

oesophageal cancer (grade B). Neoadjuvant chemotherapy with cisplatin and

5-uorouracil (5-FU) improves short term survival oversurgery alone (grade B).

There is no evidence to support the use of preoperativeradiotherapy in oesophageal cancer (grade A).

Preoperative chemoradiation may improve long termsurvival (grade B).

Chemoradiation is the denitive treatment of choice forlocalised squamous cell carcinoma of the proximal oesoph-agus (grade B).

Gastric cancer 5-FU is the most active chemotherapeutic agent. A

combination of 5-FU with other agents is superior to singleagent treatment. The combination of epirubicin, cisplatin,and continuous infusion of 5-FU (ECF) appears to be one of the most active regimens (grade B).

Adjuvant chemotherapy/chemoradiotherapy are currentlynot standard practice for resected gastric cancer and shouldbe offered only within the setting of a clinical trial (grade A).

Intraperitoneal chemotherapy remains investigational(grade B). Neoadjuvant chemotherapy remains investigational withno denite evidence of survival benet and clinical trials arecontinuing (grade B).

Palliative treatment Palliativetreatmentshouldbeplannedby themultidisciplin-

ary team with direct involvement of the palliative care teamand the clinical nurse specialist (grade C).

Oesophageal cancer Dilatation alone should be reserved for patients who are

considered to have an extremely short life span (four weeksor less) and unable to swallow saliva, or as a very short termmeasure to relieve dysphagia while more denitive treat-ment is planned (grade B).

Injection of tumour with 0.51 ml aliquots of 100% alcoholshould be considered in the following situations: (a) For eccentric or soft exophytic tumours, unsuitable for

endoscopic intubation (grade B). (b) Tumours too close to the cricopharyngeus for

endoscopic intubation (grade B). (c) For treatment of tumour overgrowth at the ends of an

oesophageal prosthesis (grade B). Oesophageal intubation is the treatment of choice for rm

stenosing tumours (capable of retaining an endoprosthe-sis), more than 2 cm from the cricopharyngeus,where rapidrelief of dysphagia in a one stage procedure is desirable(grade B).

Expandable metal stents are preferable to plastic tubes in view of the lower complication rate at insertion and shorterhospital stay (grade B).

Covered expandable metal stents or cuffed plastic tubes arethe treatment of choice for malignant tracheoesophagealstulation or following oesophageal perforation sustainedduring dilatation of a malignant stricture (grade B).

Laser treatment is effective for relief of dysphagia inexophytic tumours of the oesophagus and gastric cardiaand in treating tumour overgrowth following intubation(grade A).

For patients whose dysphagia is palliated using lasertherapy, the effect can be prolonged substantially by usingadjunctive external beam radiotherapy or brachytherapy(grade A).

Chemoradiation provides a survival benet over radio-therapy alone (grade B).

Radiotherapy or chemotherapy alone palliate dysphagiamore slowly than intubation or laser treatment (grade B).

Both photodynamic therapy (PDT) and argon plasmacoagulation (APC) are experimental and their use is notcurrently recommended (grade B); there may be a role for APC in treating tumour overgrowth of stents (grade C).

Gastric cancer

Palliative chemotherapy for locally advanced and/or meta-static disease provides quality of life and survival benet(grade A).

Currently there is no indication to recommend second linechemotherapy. Its role should remain in the context of aclinical trial (grade B).

Downstaging of locally advanced disease with chemo-therapy is possible in individual cases, with anecdotalreports of prolonged survival following complete surgicalresection. However, no randomised trials have beenconducted to demonstrate a survival advantage from addi-tion of surgery following palliative chemotherapy (gradeC).

Follow up In the absence of randomised controlled trials, the most

persuasive arguments for follow up are patient support andaudit. Audit should be structured with particular referenceto outcome measures and should be regarded as a routinepart of the work of the multidisciplinary team (grade C).

The development of a role for clinical nurse specialists infollow up should be actively pursued (grade C).

EPIDEMIOLOGY AND AETIOLOGY Oesophageal cancer Descriptive epidemiologyRecent UK data for the mid 1990s indicate that there are anestimated 7000 new diagnoses and 6700 deaths fromoesophageal cancer each year. 2 3 The overall age standardisedincidence has increased over recent decades especially amongadenocarcinomas (ACA) close to the gastro-oesophageal junc-

tion. Data from the Ofce for National Statistics shows thatthe incidence for men and women in England and Wales is12.6 and 5.9 per 100 000, respectively. 4 Oesophageal cancer isessentially a disease of older age, with two thirds of casesbeing diagnosed over 65 years of age. 4 The aetiology of oesophageal cancer appears to be different for each histologi-cal subtype and independent of this for different geographicalregions. The two major groups are squamous cell carcinoma(SCC) and ACA.

Alcohol and smokingCase control studies suggest that, in the West, SCC is stronglyrelated to smoking and alcohol consumption whereas in otherparts of the world such as China the aetiology is more

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complex. 5 In the USA the risk of both SCC and ACA isincreased by both smoking and alcohol although the increaseis much greater for SCC (odds ratio 16.9 v 3.4; 9.5 v 1.8,respectively). 6 In Europe, the Americas, South Africa, north-east China, and Hong Kong, case control studies have show asynergistic dose dependent effect of both smoking and alcoholconsumption, 710 the risks increasing substantially in those who both smoke and drink. Smokers of pipes, hand rolled, andhigh tar cigarettes have the highest risk among smokers.

Dietary factorsDiets lacking in vegetables, fruit, and dairy products, with lowintakes of vitamins A, C, and riboavin have been shown topredispose to oesophageal squamous cancer. 1113 Increased riskis also associated with consumption of pickled vegetables. 14

Iron deciency anaemia through the Paterson-Brown-Kellysyndrome is also associated with squamous carcinoma of theoesophagus. In the West, nutritional deciency is less likely tobe important in the aetiology of oesophageal cancer. ACA, per-haps through gastro-oesophageal reux, appears stronglyassociated with obesity, one recent study reporting an oddsratio of 7.6 in patients with a raised body mass index. 15

Gastro-oesophageal refluxGastro-oesophageal reux is complicated by Barretts oesoph-agus in 614% of patients. Case control studies have shown atwofold relative risk of developing ACA of the oesophagus with reux oesophagitis, 16 the risk increasing with duration of symptoms, 17 particularly in male caucasians. Recent evidencehas shown that longstanding severe symptoms of reux areassociated with an increased risk of ACA, with an odds ratio of 44. 18

Achalasia Achalasia predisposes to squamous carcinoma of the oesoph-agus. The apparent risk of cancer is highest in the rst yearfollowing diagnosis, probably because prevalent cancers leadto dysphagia, prompting the initial diagnosis of achalasia.Subsequently there is a 16-fold increase in the risk of develop-ing SCC. Patients with achalasia should be aware of the risk of oesophageal cancer. The role of endoscopic surveillance isuncertain. A population based study estimates that 406 endo-scopies in males and 2220 in females would be required todetect one case of oesophageal cancer. 19 Furthermore, thereare no data to suggest that even these rates of detection wouldimprove prognosis. However, the increased risk is a commonfeature of other studies and other factors including durationof symptoms and degree of food retention need to beevaluated to dene high risk patients. 20 21

Primary preventionElimination of any aetiological factors from a population inorder to try to minimise the chance of malignant transforma-tion in the oesophagus cannot be fully achieved as the precisesequence of events involved in the development of oesopha-geal cancer has not been fully elucidated. Public health educa-tion programmes should encourage reduction in smoking and

avoidance of excess alcohol intake. A diet rich in fruit and vegetables should be encouraged with up to ve servings perday .

Reduction in gastro-oesophageal reux may be achieved bysuppressing gastric secretion pharmacologically or by surgery.It has not been convincingly demonstrated that suchmeasures might reduce the risk of oesophageal ACA,althoughthis is the subject of an international prospective randomisedstudy in patients with Barretts oesophagus.

Gastric cancer Descriptive epidemiologyGastric cancerremains a relativelycommon malignancy in theUK. Recent UK data for the mid 1990s indicate that there are

an estimated 10 000 new diagnoses and 7500 deaths fromgastric cancer each year. 2 3 The overall age standardisedincidence has shown a steady decrease over the past few dec-ades. However, this has had relatively little impact on the workload associated with gastric cancer, which has remainedfairly constant, reecting the ageing population. 22 Data fromthe Ofce for National Statistics show that the incidence formen and women in England and Wales is 20.4 and 7.4 per100 000, respectively. 4 Gastric cancer is essentially a disease of older age, over 80% of cases being diagnosed after 65 years of age 4 although a regional survey suggested that early gastriccancer (disease limited to the mucosa and submucosa) gener-ally affects a population approximately 10 years younger thanmore advanced disease. 23 In the UK, as elsewhere, theincidence of gastric cancer is strongly associated with poorsocioeconomic status and this largely explains the geographi-cal pattern of disease, with higher rates in the north of England, Wales, and Scotland.

Anatomical locationThere has been an intriguing change in the anatomical subsitedistribution of gastric cancer, with a trend for tumours to befound more in the proximal stomach, particularly around thecardia, and a reduction in the incidence in the distalstomach. 2426 There has been an absolute increase in tumoursin the cardia region and this has led to the suggestion thatsuch cancers, along with ACA of thelower oesophagus, maybeassociated with gastro-oesophageal reux. 18

Gastritis as an aetiological factorChronic inammation of the gastric mucosa can lead to intes-tinal metaplasia and gastric atrophy, which are believed to beimportant precursors for malignant transformation. 27 Patients with pernicious anaemia and those who have had previousgastric resection for benign disease were the rst examples of this association. 28 29 In the last decade there has been increas-ing evidence for the role of Helicobacter pylori infection. Thisorganism causes a persistent active gastritis which usuallybecomes chronic and may progress to atrophy. There is anincreased risk of gastric cancer in H pylori infected individuals which has been assessed as 26-fold. 3032 Recent meta-analyses

conclude that the risk is approximately 2.53335

although this isincreased for non-cardia cancers and possibly by infection with specic pathogenic strains of the bacterium. 32 Therelationship between infection and cardia cancer is currentlyunclear but there is a suggestion that eradication of H pylorimay increase the risk of cardia cancer.

Dietary factorsThere is much evidence to suggest that diet plays an importantrole in the aetiology of gastric cancer. In particular, diets con-taining low levels of fresh fruit and vegetable consumptionincrease the risk of this disease. 36 37 Dietary antioxidants maybe the critical components of fruit and vegetables that are of aetiological importance. For example, in Venezuela, Munozand colleagues 38 found a reduced incidence of intestinal meta-plasia in populations given a diet enriched in carotene and

vitamins C and E. It is also worth noting that the vitamin Ccontent of the gastric mucosa of H pylori infected subjects islower than that in healthy mucosa. 39 A high level of saltconsumption 40 and a diet heavily dependent on preservedfoods have also been postulated as important risk factors. 36 37

Smoking As with a number of malignancies, smoking has been associ-ated with an increased risk of gastric cancer although themagnitude of the risk is not as large as that for lung cancer. 41

Familial riskGastric cancer families have been identied and there isknown to be a small (23-fold) elevated cancer risk imparted


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to rst degree relatives of gastric cancer patients. 42 This is sup-ported by the link of germline E-cadherin mutations to somefamilial gastric cancers. Although this is suggestive of aninherited factor, the familial risk could also representexposure to the same environmental inuences.

Primary prevention A diet with high intakes of fruit and vegetables (at least veservings per day) and, thereby, a satisfactory intake of antioxidants is generally appropriate health advice and likely,although not as yet proven, to reduce the incidence of gastriccancer. The increased risk of gastric cancer associated with H pylori infection inevitably encourages the concept of a screen-ing and eradication programme. It is not known however whether the mucosal changes induced by longstanding H pylori infection are reversible and whether eradication willtherefore inuence the development of cancer.

DIAGNOSIS OF OESOPHAGEAL AND GASTRICCANCERSymptomatic presentation is a poor predictor of pathology 43 44

as dyspepsia is very common. 45 Awareness of at risk individuals is essential to facilitate early referral for assessment. 46

Recent guidance for symptomatic referral from the UK Department of Health 47 has specied the at risk symptoms which a general practitioner should use to seek specialist helpto aid earlier diagnosis (table 1). It is recommended that thespecialist should see such patients within two weeks of thegeneral practitioner deciding the patient might have cancerand making the referral.

These recommendations reect a pragmatic approach forsymptomatic patients. However, there are specic areas asdescribed below where such guidance may be modied. Thereis little data to suggest that a referral within two weeks willimprove outcome quantitatively. Gastric cancers conned tothe mucosa and submucosa have a doubling time of 1.510

years whereas advanced cancer has a doubling time of between two months and one year. 46 48 Reducing symptomaticdelay is unlikely to signicantly alter prognosis for earlydisease but in more advanced disease a small proportion maybe amenable to potentially curative surgery. Appropriate auditis required to determine if overall survival can be improved bythis approach.

The principal method of diagnosis in upper gastrointestinalcancer is endoscopy. The advantages of endoscopy are thatbiopsies can be taken and small lesions evaluated more fullythan is possible with radiological studies. 49 Radiology alone will miss a high proportion of early oesophageal cancers 50 andother pathology such as foreign body reactions can mimicneoplastic disease. 51

However, there is very little evidence that any diagnosticprocedure affects outcome. 52 Most studies have concentratedon early referral and ease of access for symptomatic patients.Several observational studies infer that open access endoscopyresults in more cases of early stage disease, particularly gastriccancer. 53 Other observational studies qualify this nding byhighlighting the fact that open access results are heavilyinuenced by referral bias and that the majority of cases of gastric cancer still present at a late stage. 54

SymptomsOesophageal cancerThe principal symptom of carcinoma of the oesophagus isdysphagia. Observational studies show that cancer accountsfor one quarter of all patients presenting with truedysphagia 55 and as such all patients with this symptom shouldbe referred urgently for endoscopy or barium studies.

The increase in the incidence of ACA reects the predomi-nance of gastro-oesophageal reux disease. Estimates suggestthat 49% of adults experience daily heartburn and up to 20%experience symptoms on a weekly basis. Early assessment of such patients should be considered prior to starting empiricaltreatment as approximately 60% of patients with malignantdisease localised to the submucosa are symptomatic atpresentation. 56 Lagergren and colleagues 18 have estimated therisk of developing ACA of the oesophagus by scoringsymptoms of heartburn and regurgitation (alone or in combi-nation), timing of symptoms, particularly occurring at night,and frequency of symptoms. Among those with recurrentsymptoms of reux the odds ratio of developing cancer were7.7 in comparison with those without symptoms. Morefrequent, more severe, and longer lasting symptoms of reux were associated with a greater risk (odds ratio 44).

Gastric cancerEarly gastric cancer Early gastric cancer is dened as ACA conned to the mucosa

or submucosa, irrespective of lymph node invasion. Observa-tional studies indicate that approximately 70% of patients with EGC have symptoms of uncomplicated dyspepsia 57 58 andare not complicated by anaemia, dysphagia, or weight loss. 59

Other studies have conrmed the benign nature of symptomsin early stage disease. 53 54 Clinical diagnosis is very inaccuratein distinguishing between organic and non-organicdisease 60 61 and therefore all at risk patients with dyspepsiashould be considered for endoscopy even though the overalldetection rate is only 12%. 62

Advanced gastric cancer The majority of patients present with advanced disease withalarm symptoms such as weight loss, vomiting, anorexia,

Table 1 Upper gastrointestinal cancers: guidelines for referral47

Dysphagia Dyspepsia combined with one or more of these alarm symptoms:

Weight lossAnaemiaAnorexia

Dyspepsia in a patient aged 55 years or more with at least one of the following high risk features:Onset of dyspepsia less than one year agoContinuous symptoms since onset

Dyspepsia combined with at least one of the following known risk factors:

Family history of upper gastrointestinal cancer in more than one first degree relativeBarretts oesophagusPernicious anaemiaPeptic ulcer surgery over 20 years agoKnown dysplasiaAtrophic gastritisIntestinal metaplasia

Jaundice Upper abdominal mass


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abdominal pain, and anaemia. 59 In the UK, delays in diagnosisoccur as a result of failure to investigate at risk patients withupper gastrointestinal symptoms. 46 Such patients often have along history of dyspepsia prior to being referred. 54 Treatment with antisecretory therapy may also delay diagnosis or resultin a misdiagnosis on rst endoscopy. 54 63 In particular, the abil-ity of proton pump inhibitors to heal malignant ulcers hasnot been fully appreciated. 63 64 Thus a diagnosis needs to beestablished before such agents are used in at risk patients.

DiagnosisThe diagnosis of oesophageal and gastric cancer should alwaysbe conrmed by breoptic video endoscopy although bariumstudies may have been used as the primary investigation.Rigid oesophagoscopy is no longer recommended as exibleendoscopy is safer and more cost effective. 65 The specicity of barium studies versus primary endoscopy is similar 49 butendoscopy allows for biopsy and cytology, which are essentialfor conrming the diagnosis. 66

There are no randomised trials to show a benet of endos-copy over barium studies but it has been suggested thatincreasing the ease of investigating late onset dyspepsia couldincrease the proportion of early gastric cancers to 26%. 57 Simi-lar gures have been reported from Leeds and attributed toopen access endoscopy. 53 Other observational studies qualify

this nding by highlighting the fact that open access resultsare heavily inuenced by referral bias and that the majority of cases of gastric cancer still present at a later stage. 54

Barretts oesophagus and dysplasiaThe diagnosis of Barretts oesophagus is based on a combina-tion of visual appearance and standard biopsy specimens.Before the recognition of short and ultrashort Barrettsoesophagus, it was possible to make the diagnosis on theobservation of more than 3 cm of gastric metaplasia above thegastro-oesophageal junction. Shorter segment specialisedcolumnar epithelium is dened as intestinal metaplasia in acolumnar lined segment less than 3 cm in length. Intestinalmetaplasia at the cardia, which is only detectable histologi-cally, has been referred to as ultrashort segment Barrettsalthough its malignant risk is lower as it is more likely to beassociated with H pylori than gastro-oesophageal reuxdisease.

The key point for the endoscopist is thus to be able torecognise which area to biopsy. The European Society of Gastrointestinal Endoscopy has recently published minimumstandard terminology in digestive endoscopy. 67 The length of Barretts oesophagus has been dened as the distancebetween the transition from oesophageal mucosa to gastricmucosa (Z-line) and the upper end of the gastric folds, theposition of the Z-line being recorded in centimetres from theincisors. Thus biopsies of this area are all important inconrming the diagnosis.

High grade dysplasia warrants urgent review of endoscopy with repeat biopsy and, if conrmed, careful considerationshould be given to resection as in such patients re-evaluation

will demonstrate malignant change in up to 40%. Areas of high grade dysplasia and microscopic ACA can bedetected by multiple four quadrant biopsies of the oesophagusat 2 cm intervals throughout its entire length. 68 Sampling canalso be improved by taking jumbo biopsies of the oesopha-geal mucosa 69 but even this technique may miss unsuspectedBarretts cancers. 70

The role of surveillance endoscopy in patients withestablished Barretts is controversial. Oesophageal cancersarising in Barretts detected by surveillance areoften early andhave an excellent prognosis. However, studies have reportedlarge numbers of endoscopies with little effect on diagnosisand overall survival. 71 It remains to be established if those withrisk factors such as ethnic origin, long segment metaplasia,

male sex, smokers, and high alcohol intake are a more appro-priate group for surveillance (cf British Society of Gastroenter-ology Guidelines on Barretts oesophagus)

Biopsy An endoscopic diagnosis of malignancy must be conrmedpathologically. Histology is the preferred method and theaccuracy of diagnosis increases with the number of biopsiestaken. 72 Cytology can be used to complement histology butthere is no evidence to show that cytology is better than biopsy

alone. Indeed as in oesophageal cancer, a positive cytologyresult alone is insufcient evidence to proceed to denitivetreatment for gastric cancer.

Preoperative stagingAim Accurate staging of gastro-oesophageal tumours is essential toallow a well informed decision to plan appropriate treatment(table 2). 73 Advances in non-surgical management of advanced tumours demand accurate staging. Such precise stagedependent management will limit the incidence of unneces-sary exploratory surgical interventions. Accurate tumourstaging is also clearly important when comparing outcomes of various non-surgical interventions as there is no pathologicalgold standard. At the other end of the disease spectrumthere is also a requirement for accurate local tumour staging:small supercial early oesophagogastric cancers can some-times be removed endoscopically but knowledge of the precisedepth of tumour penetration and exclusion of more distantspread are essential prerequisites. Preoperative investigationsthat do not inuence management decisions should beavoided.

MethodsModalities for staging of oesophageal and gastric cancershould include spiral computed tomography (CT) andendoscopic ultrasound (EUS). Modalities and techniques thatshould be available for use in selected cases include chestradiography, trans-abdominal ultrasound, magnetic reso-nance imaging (MRI), bronchoscopy, and laparoscopy.

Computed tomographySpiral contrast enhanced scans with thin collimation (5 mm)is optimal. Tumours at the cardia and within the stomach arebest demonstrated following gastric distension with 600800ml of water. Distal body and antral tumours are best evaluatedin the prone position.

T staging of the oesophagusCT cannot delineate the component layers of the oesophageal wall and therefore is unable to differentiate between T1 and T2lesions. CT cannot detect microscopic invasion in T3 tumoursand differentiating macroscopic T3 from focal tumour bulgingor juxtalesional lymphadenopathy can be impossible, particu-larly in cachectic individuals. 74 Understaging is more commonthan over staging. CT ndings suggesting T4 involvement of the aorta, tracheobronchial tree, and crura are well docu-

mented but the signs are soft leading to poor sensitivity when compared with EUS. However, CT can predict media-stinal invasion in over 80% of patients. 7579

T staging of the stomach Adequate gastric distension is required for CT to identify theprimary lesion and determine the extent of the abnormal wallthickness. Achieving this distension can be problematic inpatients with advanced gastric carcinoma.

CT cannot differentiate between T1 and T2 lesions. T3lesions can be suggested by identifying stranding into theadjacent perigastric fat but differentiating between trans-mural extension and perigastric lymphadenopathy can be dif-cult. Most contemporary studies report accuracy of 8088%


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in identication of patients with advanced disease. 8082 T4diagnosis on CT relies on the presence of contact betweentumour and contiguous organs, a focal loss of intervening fatplane, or clear CT evidence of direct organ invasion. Thesesigns may be difcult to evaluate in the cachectic patient. 83 84

Endoscopic ultrasoundOesophagusThe ability to identify the component layers of the bowel wallprovides the basis for tumour staging. EUS is superior to CTfor local staging of oesophageal tumours 76 85 86 and is moreaccurate in predicting resectability although the complemen-tary nature of these imaging techniques must beemphasised. 87 88 Non-traversable stenotic oesophageal tu-mours at initial endoscopy require dilatation, preferably underimage intensication. Such tumours are highly likely to bestage T3 or greater. 89 The 8.5 mm blind oesophagoprobepassed over a guidewire is useful in stenotic tumours 90 andtechnological improvements have overcome limitations re-lated to the assessment of the depth of penetration.

StomachEUS is superior to CT for the local staging of gastriccarcinoma 91 although the complementary nature of theseimaging techniques must be emphasised. Higher frequencytransducers can evaluate the subgroups of T1 and assess thesuitability for endoscopic mucosal resection. The presence of direct invasion into adjacent structures (T4) can be assessedon EUS by demonstrating xity.

A potential pitfall in staging is tumour penetration throughthe muscularis propria extending into the greater or lesseromenta but without penetration of the overlying visceral peri-toneum. The TNM classication 73 denes this as T2. However,the omental reections around the stomach are not clearlyseen with EUS and this classication raises important issuesfor EUS staging of gastric carcinomas. It is difcult or impos-sible to know if a carcinoma has penetrated the muscularispropria into the greater or lesser omenta but not breached the visceral peritoneum beyondthat is, ?T2 or ?T3. As in theoesophagus, there are a smaller but signicant number of non-traversable stenotic tumours that prevent a full EUSevaluation 92

N stagingCT scanningSize is the only criterion for assessment of lymph nodes and isa poor predictor of involvement, particularly in the chest, where large nodes may be reactive. The accuracy of CTdiagnosis of mediastinal node involvement ranges from 38%to 70%. If nodes over 8 mm in diameter are considered abnor-mal in the coeliac axis, a sensitivity of 48% and a specicity of 93% is achieved. 77 Identication of more distant nodal groupsis of particular importance as these nodal groups may not beamenable to evaluation with EUS and will often be outside theborders of even a radical resection.

The revised TNM classication has changed the classi-cation of nodal involvement in gastric cancer. Previous classi-cations emphasised the importance of the distance of theinvolved nodes from the primary tumour. However, thecurrent classication places emphasis on the number of involved nodes. Stage N1 refers to metastases in 16 regionalnodes, N2 715 nodes, and N3 involvement of more than 15nodes. All published papers addressing the accuracy of EUSand CT in the staging of gastric cancer utilise the old TNMclassication. The impact of these changes on the accuracy of current imaging modalities remains to be seen.

Endoscopic ultrasound Lymph nodes are well seen and certain features have beenshown to correlate well with malignant inltration. Nodes with well dened margins greater than 1 cm in diameter,rounded, and hypoechoic are likely to be involved. 92 93

Malignant nodes unfortunately may not demonstrate all fourfeatures, and large benign reactive nodes are well recognised.EUS guided ne needle node aspiration cytology may behelpful 94 95 although the limitations of a negative result mustbe understood. Involved coeliac axis lymph nodes suggestingM1a disease from an oesophageal primary can be readilyidentied.

The NHS health technology assessment systematic reviewof endoscopic ultrasound in gastro-oesophageal cancer 96 con-rms the high accuracy of EUS for T and N staging of oesophageal and gastric cancer.Initial indications suggest thatthe performance for T staging at the cardia is less good. Radialprobes performed better than linear probes in staging gastriccancer although in staging oesophageal cancer there was no

Table 2 TNM classification of oesophageal and gastric cancer73

Classification Oesophagus Gastric

T1 Lamina propria, submucosa Lamina propria, submucosaT2 Muscularis propria Muscularis propria, subserosaT3 Adventitia Penetrates serosaT4 Adjacent structures Adjacent structures

N1 Regional nodes 16 nodesN2 715 nodesN3 >15 nodes

M1 Distant metastasis Distant metastasis

Tumours of lower oesophagusM1a Coeliac nodesM1b Other distant metastasis

Tumours of mid thoracic oesophagusM1b Distant metastasis including non-regional

lymph nodes

Tumours of upper thoracic oesophagusM1a Cervical nodesM1b Other distant metastasis


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signicant difference between the two probes. Staging formetastases using EUS alone is not satisfactory.

M staging A review of 838 cases of newly diagnosed oesophageal cancersrevealed that 18% have metastases at presentation 97; 45% of metastases were in abdominal lymph nodes and 18% in cervi-cal lymph nodes. In addition, 35% of metastases were hepatic,20% pulmonary, 9% bone, 5% adrenal, 2% peritoneal, and 2%cerebral. In this series, all patients with bone and brainmetastases were associated with metastatic disease in theabdomen and thorax. Hence, in the absence of clinical indica-tions, evaluation of metastatic disease should be focused onexamination of the thorax and abdomen.

The revised TNM classication 73 includes some importantchanges relating to metastatic disease in gastro-oesophagealcarcinomas. Tumours in the lower oesophagus with involvedcoeliac axis nodes or tumours in the upper oesophagus withinvolved cervical nodes are classied as M1a. Tumours of anyregion with other more distant metastases are classied asM1b. There is therefore overlap in the process between Nand M staging.

Spiral CT has signicantly improved the detection of hepaticmetastases by the introduction of techniques using thinner col-limation, overlapping slices, and dual phase imaging and will

detect7580% of metastases.98

However, in patients with knownmalignancy, only 50% of lesions less than 1.5 cm 99 and 12% of lesions less than 1 cm 100 are metastatic deposits. Small volumeascites can also be readily demonstrated with EUS, alerting thesurgeon to the possibility of diffuse peritoneal spread.

Chest radiography A chest x ray should only be requested in accordance with theRoyal College of Radiologists guidelines 101 and while the pres-ence of a known malignancy suggests such a requirement, CT will be performed as part of the routine staging procedure andis far more sensitive for the detection of pulmonarymetastases.

Transabdominal ultrasound Liver ultrasound may be more appropriate than CT when thereis good clinical evidence of liver metastases and treatmentoptions are so limited that conrmation is all that is requiredprior to palliation. Ultrasound mayalso be used in conjunction with or as an alternative to MRI to help characterise indeter-minate liver lesions identied using CT. Its routine use is notrecommended.

MRI To date there is no evidence that MR has advantages over spi-ral CT in T stage assessment of either oesophageal or gastriccarcinoma. 102 103 MR imaging of the liver may be used inspecic cases such as in patients with documented allergy tointravascular contrast agents or to help characterise indeter-minate liver lesions identied using CT. 104 Reports of the use of endoluminal MR are largely laboratory based and the few

clinical studies have shown no advantage over EUS.

Bronchoscopy CT and EUS combined are highly accurate in the assessmentof tracheobronchial invasion from oesophageal tumours andbronchoscopy is not routinely required. It should however beavailable for use in patients where such imaging has raisedsuspicion but not certainty of such invasion.

Laparoscopy Peritoneal disease can be difcult to detect with conventionalimaging. Laparoscopy should be considered in those patients where there is suspicion of peritoneal spread on CT or EUSsuch as in the presence of small volume ascites. Its routine use

following CT and EUS prior to consideration of radical resec-tion is advocated in gastric cancer and in those gastro-oesophageal junctional tumours where there appears to be agastric component. 105107

PATHOLOGY Oesophageal cancer Precursor lesionsOesophageal dysplasiaThe presence of dysplasia in squamous epithelium suggestspotential for malignant transformation. High grade dysplasiasuggests malignant transformation has already occurred.

Barretts oesophagus Although Barretts oesophagus is a well recognised entity, thepathological interpretation can be problematical. In essenceBarretts is characterised by three histological types: (i) gastricfundal type epithelium with mucous secreting cells; (ii)gastric junctional type epithelium with mucous secretingcells; and (iii) specialised columnar epithelium with mucoussecreting goblet cells amounting to intestinal metaplasia.Macroscopically, most consider columnar epithelium over3 cm or more above the gastro-oesophageal junction asBarretts. However, Barretts change can also affect segmentsless than 3 cm and may occur with or without intestinal

metaplasia. The presence of intestinal metaplasia confers therisk of malignant transformation. Endoscopically, the changesappear as an irregular edge of pink mucosa with interspersedtongues of columnar epithelium in otherwise normal palesquamous epithelium.

The main signicance of Barretts oesophagus is thetendency to mucosal instability and the development of dysplasia which may progress to cancer. 108 There is a tendencyfor longer segments to have a higher rate of dysplasia. Lowgrade dysplasia carriesan increasedrisk of progressing to highgrade dysplasia and malignant transformation. However, lowgrade dysplasia may undergo spontaneous regression. Indeedthere can be regression associated with proton pumpinhibitors with healing leaving a regenerative inammatoryatypia, which can be confused with high grade dysplasia.There are also problems with sampling error at biopsy andensuring during endoscopic surveillance that the same area isbiopsied. 109 This is further complicated by an apparent incon-sistent spatial relationship between the areas of dysplasia andareas of cancer in the same oesophagus. Such factors have ledto a lack of agreement between pathologists as to the deni-tion of dysplasia. More accurate markers are required for theloss of growth regulation in the specialised columnarepithelium of Barretts and developments in molecular andchromosomal techniques may aid a more uniform approach.

Biopsy reportingBiopsy specimens should be examined by an experienced his-topathologist. Any unusual ndings such as high gradedysplasia in Barretts should be corroborated by a separatepathologista lead pathologist in gastrointestinal patho-

logy. Cytological examination should be performed by anexperienced cytopathologist. Unusual tumour types, althoughrare, may require further investigation. If possible, thepresence of submucosal invasion should be identied in abiopsyspecimenas this increases thelikelihood of lymph nodemetastases. 110

Surgical specimen reportingReporting surgically resected specimens for oesophageal can-cer should include the principal prognostic factors. These aredetailed in the Royal College of Pathologists minimum datasetfor the reporting of oesophageal tumours. 111 Briey, a reportshould include comments on the type of tumour, depth of invasion (using the TNM staging system 73), involvement of the


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resection margins, vascular invasion, 109 and lymph nodeinvolvement. There is currently limited evidence that involve-ment of the circumferential resection margin indicates a worse prognosis. 112 Where possible, involvement of this marginshould be specied (separate dissection of the lymph nodes bythe surgeon before sending the specimen to the pathologydepartment may make examination of this margin impossi-ble). There is a widespread network of lymphatic vessels in theoesophagus allowing intramural spread of tumour which maynot be macroscopically evident. Satellite nodules of tumourmay be very close to the proximal resection margin in spite of good macroscopic clearance. 113

Gastric cancer Precursor lesionsGastritis and intestinal metaplasiaThere is now a large body of evidence to support the Correahypothesis 27 of a progression from chronic gastritis to gastricatrophy with intestinal metaplasia to dysplasia prior to malig-nant transformation. Some of the early relationships betweenthese changes are reversible. Gastric mucosa shows atrophy with age.

The relationship between the three types of intestinalmetaplasia and the intestinal type of gastric cancer is atpresent unclear. Types 1 and 2 or complete intestinal metapla-sia tend to be associated with ageing gastric atrophy and havea minimal chance of malignant transformation. Type 3 orincomplete intestinal metaplasia has a greater chance of pro-gression to dysplasia. 114

DysplasiaThe grading of gastric dysplasia is subjective and open to sig-nicant interobserver variation. To simplify (from the previousmild moderate and severe dysplasia) and to overcome thisproblem, low and high grade groupings are used. 115 Patients with high grade dysplasia on more than one examination are very likely to have an ACA. 116 However, the diagnosis of dysplasia is difcult and can be confused with regenerativechanges. Consideration of referral of biopsies with severe dys-plasia to a reference pathologist or pathologists should beencouraged. Reference pathologists are linked to the BritishSociety of Gastroenterology, the Medical Research CouncilGastric Planning Group, and the UK National BarrettsOesophagus Registry.

Biopsy reportingThe majority of diagnoses are obtained from standard H and Epreparations. Endoscopic biopsy can be supplemented bybrush cytology. In patients with anaplastic tumours, immuno-cytochemical staining should be available to differentiate fromlymphoma.

Peritoneal washings taken at laparoscopy need to be exam-ined cytologically and can provide valuable information aboutfree peritoneal cells. This is signicant as patients with freeintraperitoneal cells have a poor prognosis with disseminatedintraperitoneal recurrenceand should be considered incurableby surgery alone. 117

Surgical specimen reportingThe principal prognostic factors for gastric ACA are the depthof penetration of the tumour and lymph node involvement. 117

In addition, the macroscopic appearance (Borrman type),tumour location, and histological differentiation are impor-tant prognostic variables. The resection margins of thespecimen need to be examined and reported.

The assessment of lymph nodes should include a fulldissection of the specimen to dene the total lymph nodenumber removed and the total involved by tumour. The TNMstaging system 73 allocates nodal stage according to thenumberof lymph nodes involved. Most specimens will contain a mini-mum of 12 nodes for examination.

Malignant tumours of the stomach are usually ACA although 10% comprise lymphoma, leiomyosarcoma, and car-cinoid. A range of classications have been suggested for gas-tric ACAMing (which classies the tumour border as beinginltrative or expansile), WHO (with a range of histopathol-ogy descriptions), Goseki (dividing tumours according to whether they have good tubal formation and intracellularmucin), and Lauren (diffuse, intestinal, and mixed types). TheLauren classication is the most widely used but only identi-es a relatively small subgroup of poor prognosis gastric ACA (the diffuse carcinomas). Other factors, which have beenassessed, include vascular invasion and perineural invasion. Vascular invasion is an independent prognostic variable incardial 118 and distal tumours. 119 Perineural invasion is of ques-tionable value and requires more specic denition. 120

Oesophagogastric junction cancers ACA arising at the oesophagogastric junction pose manyproblems. They are difcult to classify as they can arise fromthecolumnar lined lower oesophagus, from thecardia itself,orfrom the gastric body/fundus, with upward spread to involvethe oesophagus. The surgical procedures advocated to treatthese tumours remain varied and controversial. True cardiatumours behave in a more aggressive fashion than oesopha-geal tumours. 118 121

The Japanese Society for Esophageal Disease 122 originallyclassied carcinomas of the gastro-oesophageal junction asE=C, where equal parts of the tumour lie within the oesoph-agus and stomach,and is eitherEC or CE where the bulkof thetumour lies in the oesophagus and stomach, respectively.Compton and Sobin 123 have proposed that if more than 50% of the tumour involves the stomach then it should be regarded asgastric while if more than 50% is within the oesophagus thenit should be reported as an oesophageal tumour. Thosetumours of equal proportions above and below the junctionare classied according to their histology and then subdividedinto either oesophageal or gastric. Squamous, small cell, andundifferentiated tumour types are regarded as oesophageal while ACA (including Signet ring type) are classied asgastric. This classication is an oversimplication as it doesnot identify true tumours of the cardia itself.

Siewert and Stein124

have proposed a classication based onthe three origins of oesophagogastric tumours mentionedabove. Their type I tumour is an ACA of the distal oesophagus,the centre of the tumour lying 15 cm above the anatomicalcardia. A type II tumour is a true carcinoma of the cardia withits centre situated between 1 cm above and 2 cm below theanatomical cardia; the type III tumour is a gastric carcinoma with its centre between 2 and 5 cm below the anatomical car-dia. It is argued that these three types of tumours require dif-ferent surgical approaches to ensure clear surgical marginsand also because of differing patterns of lymph nodemetastases making the extent of lymphadenectomy differentfor each type of tumour. Lymphatic spread from type I lesionsoccurs in a cephalad direction to mediastinal nodes as well ascaudally to the coeliac axis, whereas type II and III lesionsmetastasise almost exclusively caudally to the coeliac axis,splenic hilum, and para-aortic nodes. 125 This classication isrecommended as it is uniform, allows data comparison fromdifferent centres, and is important for the stratication of patients in prospective studies.

PRETREATMENT ASSESSMENTCareful selection of the varying therapeutic modalities isessential. Such selection should consider not only the natureof the symptoms to be relieved but also the general medicaland psychological status of the patient. Decisions should betaken in the context of the predicted prognosis and the effectof any treatment intervention on quality of life. A close multi-disciplinary team working with integrated liaison between


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primary and secondary care is therefore required to facilitatea holistic approach to patient care. This approach must ensurethat patients are provided with the information they wish tohave, in terms that they are able to understand, and in an ef-cient and timely manner. It is recommended that a fully con-stituted specialist multidisciplinary team with careful docu-mentation of the proposed treatment plan assess all patients.

PREOPERATIVE ASSESSMENTThe likely benet derived from a particular therapy dependsnot only on the stage of the oesophageal or gastric disease butalso on the tness of the patient. The patients preoperativephysiological status is a major factor in determining outcomeafter major surgery. 126129 Although scoring systems including a variety of parameters have been evaluated, the previous medi-cal history and concurrent morbidity remain the strongestpredictors. 126

Comprehensive preoperative evaluation and assessment of the patient is mandatory before assigning the patient to a par-ticular therapeutic option. Where potential problems havebeen identied, early communication with the anaestheticteam is essential. Preoperative assessment and optimisationmay necessitate a multidisciplinary approach.

Anaesthetists familiar with the complexities of one lung ventilation and epidural anaesthesia should only undertake

anaesthesia for oesophageal surgery. In such patients peri-operative invasive monitoring should be routine. 130

Appropriate postoperative facilities for aftercare must beavailable prior to undertaking surgery. 131 132

Past medical history A detailed medical history and physical examination is a pre-requisite to the assessment of any anaesthetic and operativerisk. Cardiorespiratory disease has been identied as the com-monest coexisting disease in patients presenting foroesophagectomy. 132 Pre-existing ischaemic heart disease,poorly controlled hypertension, and pulmonary dysfunctionare all associated with increased operative morbidity, 127129 133135

particularly in the elderly and following upper abdominal andthoracic surgery. The efcacy of any medication prescribed forcardiorespiratory conditions should be evaluated at an earlystage.

The American Society of Anesthesiologists (ASA) classi-cation of physical status is well recognised. Perioperative riskincreases with increasing ASA score. Only those patients withan ASA score of 3 or less should be considered forsurgery. 134 136

Social habitsSmoking is a signicant aetiological factor in perioperativemorbidity. All patients must be encouraged to stop smokingpreoperatively. 137

Preoperative investigationsThe minimum preoperative investigations for all patientsundergoing gastric or oesophageal surgery should include

baseline haematological and biochemical proles, arterialblood gases on air, pulmonary functions tests, a restingelectrocardiogram, and a chest x ray.

Exercise capacity and testing can be informative as regardsa patients cardiorespiratory reserve. 138140

Patients with known or symptomatic ischaemic heartdisease need careful evaluation, 141 142 often in collaboration with specialist colleagues. More detailed investigations suchas exercise electrocardiography, echocardiography, thalliumimaging, and V/Q scanning may be considered appropriate insome of these patients. 143

Pulmonary complications are increased when FEV 1 isreduced by 20% or more. 144146 However, in evaluatingpulmonary function tests consideration must be given to the

fact that setting strict exclusion criteria as regards acceptable values may deny patients their only chance of curativesurgery.Pulmonary function tests must be considered in relation tothose appropriate for individual height and weight, the clini-cal ndings and arterial blood gas analysis, particularly PaO 2.

Preoperative preparationCoexisting disease All patients should be rendered optimally t in the preopera-tive period before undertaking anaesthesia for gastric oroesophageal surgery.

Pharmacological treatment of angina, hypertension,asthma, and COPD should be optimised. Preoperative chestphysiotherapy may be benecial. Where appropriate, haema-tological and biochemical abnormalities should be corrected.

Nutritional statusPatients at their ideal body weight may do better after surgery. A body mass index of less than 18.5, body weight less than90% predicted, over 20% weight loss, and a lowserum albuminare associated with an increased risk of perioperativecomplications. 136 146 Obesity is associated with increased opera-tive risk. 147

Psychological preparation All patients should be counselled about treatment options,paying particular attention to the results and limitations of surgery. A clear description of the perioperative period shouldbe given. An assessment of pretreatment symptoms on qualityof life of the patient should be carefully undertaken as there isaccumulating evidence of quality of life scores having anindependent effect on outcome. 148

Thromboembolic prophylaxis Appropriate measures should be taken against the risk of thromboembolic complications. Antithromboembolic stock-ings, low molecular weight heparin, and peroperative calf compression should be employed. 149

Antibiotic prophylaxisBroad spectrum antibiotic prophylaxis should be administeredpreoperatively, or on induction of anaesthesia, in accordance with locally agreed policies.

Blood cross matchFour units of blood should be cross matched prior to surgery.Transfusion however should be avoided if at all possible as theimmunological suppressive effect can adversely affectsurvival. 150

SURGICAL RESECTION FOR OESOPHAGEALCANCERGeneral rationaleResection of oesophageal malignancy with intent to cure isbased on the concept that if all neoplastic tissue can be

removed a worthwhile period of survival and possible curemight be achieved. Surgical therapy is the only treatment thathas repeatedly been shown to provide prolonged survival,albeit in only approximately 20% of cases. 151 The results of sur-gical resection for both early stage squamous cell and ACA canbe excellent. Five year survival rate is over 80% when tumoursare conned to the mucosa and between 50% and 80% whenthe submucosa is involved. 152 153 Conversely, resection has noplace in patients with haematogenous metastases. 154

It is essential that oesophagectomy should be undertaken with a low hospital mortality and complication rate. Caseselection, case volume, and surgical experience all play animportant part. Preoperative risk analysis has been shown tocause a reduction in postoperative mortality from 9.4% to


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1.6%. 155 In 1986, Matthews et al demonstrated a negative cor-relation between the number of carcinomas resected and hos-pital mortality among surgeons in the West Midlands. 156 A team based approach and increasing expertise within thatteam has also demonstrated a signicant decrease in the mor-tality of oesophagectomy over time. 157161

In an extensive literature review of studies reportedbetween 1980 and 1988 it was conrmed that the averagehospital mortality following resection was 13%. 151 Many Euro-pean centres have reported hospital mortalities well below this

gure throughout the 1990s and it must be accepted that ahospital mortality of less than 10% should now be achievable.

Selection of patients for surgery Patient selection for radical intervention is based on the stageand spread of the tumour and the general and specic medi-cal tness of the patient. A specialist oesophagogastric cancerteam in discussion with the patient and his/her family shouldmake treatment decisions.Patients for whom radical interven-tion is inappropriate (T4 tumours) may be best treated in localcancer units. However, the specialist oesophagogastric cancerteam should be involved in developing an appropriate careplan for these patients.

Radical surgery should be recommended for patients withlocalised (T1, T2) tumours who are sufciently t to toleratethe procedure. Combination therapy should be considered forT2 tumours (see below). Patients with advanced oesophagealcancer (T3N1) should be considered for randomised control-led studies to assess the role of novel multimodality therapiesin combination with surgery.

Choice of operative approachThe histological tumour type, its location, and extent of theproposed lymphadenectomy should determine the operativeapproach. Adequate mediastinal lymphadenectomy is essen-tial in SCC but needs to be extended to the abdomen in junc-tional ACA. This makes transhiatal oesophagectomy unsuit-able for SCC. A left thoracoabdominal approach is limitedproximally by the aortic arch which may compromise theproximal limit of resection. Tumours which lie at the level of the arch are difcult to deal with from the left side and thisapproach should be avoided when the tumour lies at this levelor higher. Themost widelypractised approach is thetwo phaseLewis-Tanner, with a preliminary laparotomy and construc-tion of a gastric tube and a right thoracotomy to excise thetumour and perform an oesophagogastric anastomosis at theapex of the mediastinum.A third cervical phase may be addedin the case of proximally situated tumours in order to achievethe requisite degree of longitudinal clearance.

Standards of tumour resection All operations should deal adequately with the local tumour tominimise the risk of local recurrence and permit an adequatelymphadenectomy, which will reduce the risk of staging error.The extent to which lymphadenectomy per se minimises therisk of symptomatic local recurrence is not known. Theevidence that more thorough lymphadenectomy is associated

with better survival may simply reect more accurate staging.Longitudinal submucosal spread is characteristic of alltypes of oesophageal carcinoma. This accounts for a high rateof resection margin positivity, when limited longitudinalresections are employed, even with negative frozen sectionbiopsy margins. 162 Extensive studies 163165 support the view thatthe proximal extent of resection should ideally be 10 cm abovethe macroscopic tumour and 5 cm distal to it, when theoesophagus is in its natural state. Local recurrence can beminimised in this situation by the use of postoperativeradiotherapy 166 and this should be considered in SCC, particu-larly when the proximal level of the tumour is high.

ACA of the lower oesophagus commonly inltrates the gas-tric cardia, fundus, and lesser curve. Some degree of gastric

excision is essential to accomplish an adequate lymphadenec-tomy in the abdomen and this should be created in such a wayas to obtain a minimum distance of 5 cm beyond the distalextent of the macroscopic tumour. It is interesting to notehowever that positive distal resection margins in ACA areoften found in patients with locally advanced disease wherethe resection in retrospect was unlikely to be curative. Most of these patients do not die from symptomatic locoregionalrecurrence. 167

Adequate radial margins should also be considered and

contiguous excision of the crura and diaphragm need to beconsidered, particularly for junctional tumours. 168

Standards of lymphadenectomy The majority of patients who undergo surgery for either ACA or SCC of the oesophagus will have lymph node metastases. 151

The principal aims of lymphadenectomy should be tominimise staging error, reduce locoregional risksof recurrenceand, by increasing the number of patients undergoing an R0resection, increase ve year survival (R0 resection: completemacroscopic and microscopic clearance). 154 169 In SCC, when amethodical approach to lymphadenectomy is applied, thenumbers of lymph nodes involved are of prognosticsignicance 170 as is the ratio of invaded to removed nodes. 169

Although there is considerable enthusiasm for the perform-ance of lymphadenectomy in three elds (abdomen, thorax,and neck) in Japan, 170 this approach has not been adopted widely by Western surgeons.

Abdominal single eld node dissection involves dissectionof the right and left cardiac node, the nodes along the lessercurvature, left gastric, hepatic, and splenic artery territories.

Two eld dissection additionally embraces thoracic lym-phadenectomy and includes the para-aortic nodes along withthe thoracic duct, para-oesophageal nodes, right and left pul-monary hilar nodes, those at the tracheal bifurcation and, inJapan, para-tracheal nodes including those along the leftrecurrent laryngeal nerve.

Three eld dissection extends the lymphadenectomy to theneck to clear the brachiocephalic, deep lateral, and externalcervical nodes, and the deep anterior cervical nodes adjacentto the recurrent laryngeal nerve chains in the neck.

A number of studies have shown that two eld lym-phadenectomy can be carried out without any signicantincrease in operative morbidity or mortality. 154 170 171

Conversely, although the three eld operation is advocatedin Japan for SCC, its benets may simply reect the reductionin staging error, as nearly a quarter of all Japanese patients will have cervical lymph node metastases. 170 There is noevidence that three eld lymphadenectomy improves survivalin patients with ACA and it must be accepted that the opera-tion is associated with a higher risk of postoperative morbid-ity (see below).

Choice of conduit, route, and anastomosisThe commonest conduit is the stomach. The function of theintrathoracic stomach as an oesophageal replacement hasbeen extensively studied. 172 The necessary vagotomy can

produce troublesome gastric paresis. A prospective ran-domised trial suggested that the addition of a drainage proce-dure did not affect gastric emptying or clinical outcomealthough it was too small to reach statistical signicance. 173

Thus since the morbidity of pyloroplasty is small, its additionshould be considered. Colon interposition is the next mostsuitable conduit when the stomach is not available. Again,functional performance has been studied in detail. 174

Most surgeons favour a prevertebral route for reconstruc-tion and this was shown to be superior to an anteriorreconstruction in one randomised study 175 although anothersmall prospective randomised comparison with a retrosternalgastric tube showed no differences in technical complicationsor functional outcome. 176


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The level at which the anastomosis is performed is the subject of continued debate. There are no randomised trials tocompare subtotal oesophagectomy with anastomosis in theneck or oesophagogastrectomy with anastomosis in the supe-rior mediastinum. Each has its proponents. Until and if such atrial is undertaken, the fundamental premise must be thepresence of clear longitudinal resection margins and anacceptable morbidity and mortality.

Both retrospective and prospective studies comparingmanual versus mechanical oesophagogastric anastomosishave shown no difference in leak rates or othercomplications. 177 178 Fewer strictures occur with handsewnanastomoses particularly single layer anastomoses. 179

Postoperative managementMeticulous attention to the maintenance of uid balance andrespiratory care are essential in the immediate postoperativeperiod. Pain control and pulmonary physiotherapy are crucial. Although some authors advocate the routine use of a feeding jejunostomy, there have been no prospective trials to examineits value. 180 Early mobilisation is important in the preventionof venous thrombosis and pulmonary embolism.

Postoperative complicationsPulmonary

Respiratory complications are common following oesophagec-tomy. Pain from extensive incisions can be a major contributorto decreased ventilation and atelectasis, leading to pneumoniaand respiratory failure. Incisions of thediaphragm may impairits movement and extensive lymphadenectomy can cause poorlymphatic drainage of the pulmonary alveoli, resulting in aform of acute pulmonary oedema. 181183 The use of thoracic epi-dural anaesthesia has been shown to signicantly decreasethe incidence of respiratory complications. 184

Anastomotic leakageEarly disruption (within the rst 72 hours) usually reectstechnical error. Once conrmed, if the general condition of thepatient is good, then re-exploration and repair is appropriate.The majority of disruptions occur later (up to two weeks) andprobably reect local ischaemia and/or tension in the anasto-motic site. A high index of clinical suspicion is important. Although water soluble contrast radiology should be used toestablish that leakage has occurred, the technique is not com-pletely accurate and may miss clinically signicant leaks as well as demonstrate radiological leakages of no clinicalsignicance. 185 186 The majority of anastomotic leakages, whether in the neck or the chest, can be managedconservatively with nasogastric suction, appropriate localdrainage, antibiotics, and jejunal feeding. Dehiscence of thegastric resection line is usually due to ischaemia and isdramatic in its presentation. Early endoscopy may be consid-ered if radiology is inconclusive. Re-exploration is essential. 187

There seems to be no real difference in clinically signicantleak rates and subsequent effects comparing neck and chestanastomoses. Placement of an anastomosis in the neck does

not guarantee that leakage will not be into the thoraciccavity. 188 The overall anastomotic leak rate should not exceed5%. 151

ChylothoraxChylothorax occurs in about 23% of transthoracicoesophagectomies. It is easily recognised as turbid creamyuid in the chest drain. The rate may be higher with trans-hiatal oesophagectomy although this is not always thecase. 189192 The condition has a high mortality if conservativetreatment becomes prolonged due to hypoalbuminaemia andleucocyte depletion. 189 The rate of chyle output on about thefth postoperative day may predict the likelihood of spontane-ous closure. Chyle production of greater than 10 ml/kg/day at

that time is an indication for early reoperation and ligation of the thoracic duct. 192

Recurrent laryngeal nerve injuryRecurrent laryngeal nerve injuries are more common duringdissection of the upper third of the oesophagus. The majorityof injuries are unilateral and transient. The left recurrentlaryngeal nerve is at risk during mediastinal lymphadenec-tomy and if cervical anastomosis is used in association withsuch a dissection, it is wiser to place this on the left side in

order to minimise the risk of damage to both recurrent laryn-geal nerves. Recurrent laryngeal nerve injury impairs thepatients ability to cough in the early postoperative period andadequately protect the airway during swallowing. It cantherefore be a potent contributor to pulmonary morbidity. Inmost patients there is adequate compensation from the oppo-site cord. Tracheostomy should be considered to protect theairway and improve pulmonary toilet. Thyroplasty or vocalcord injections are rarely required. 193

Benign anastomotic strictureThese can occur within the rst few months after surgery, where they relate to postoperative brosis, or late (that is, years), when they are due to reux. Differentiation fromsuture line recurrence can be difcult at early stages andbiopsy is essential. The incidence of early anastomoticstricture formation seems to be higher with cervical ratherthan intrathoracic anastomoses and in stapled procedures,particularly if a small circular stapler is used. 194196 These earlypostoperative anastomotic strictures are easily dealt with byendoscopic dilatation although multiple sessions may benecessary. 197

SURGICAL RESECTION FOR GASTRIC CANCERCurative surgery Surgery is the treatment of choice for gastric cancer. The mostimportant variable for resectability and survival after surgeryis the stage of disease at presentation. In the West Midlandssurvey, 80% of patients presented with stage IV disease andonly 20% underwent curative resection. 24 In a review of English language publications in the decade to 1990, Akohand Macintyre 198 reported a mean resection rate of 48% withonly 31% having curativeor R0 resection. In the UK MedicalResearch Council multicentre D1 lymphadenectomy versus D2extended lymphadenectomy trial, only 54% of patientsdeemedsuitable forinclusion within thetrial protocol actuallyunderwent a potentially curative resection. 199 The increasingavailability of endoscopy and the recommendation to investi-gate patients with new onset dyspepsia promptly has led toimproved resectability rates. 53 57

Extent of gastric resectionGastric cancer behaves as a locoregional disease with late dis-tant metastasis in a signicant proportion of cases. The Japa-nese Rules for Gastric Cancer 117 have described the criteria formargins of macroscopic clearance according to the site of the

lesion and macroscopic size. A subtotal gastrectomy is appro-priate for an early or well circumscribed T2 cancer if the proxi-mal edge is more than 2 cm from the cardia. There needs to bea 5 cm clearance for a more inltrative lesion. When theproximal distance is less than 5 cm or the tumour is diffuse with submucosal inltration, a total gastrectomy is indicated. A proximal oesophageal margin of 5 cm in the natural state isnecessary for type III junctional tumours. Total gastrectomy with abdominal lymphadenectomy should also be consideredfor type II tumours. Resection of adjacent organs when thereis denite or suspected transmural invasion (T4 cancers) maybe worthwhile provided no macroscopic residual disease willremain and the patient is t enough to undergo radicalsurgery. 200


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Less extensive resections are now commonly performed inJapan in selected patients with early gastric cancer. Theseresections may be open, laparoscopic, or using an operativegastroscope. The high incidence of node positive early gastriccancer in the West means that limited resections may not becurative. 201

Lymphadenectomy Japanese experience has shown that excision of the primarylesion together with the omenta and rst two tiers of lymphnodes (N1 and N2) that drain the affected area of the stomachcan cure patients even in the presence of lymph nodemetastasesD2 or systematic lymphadenectomy. If othernodes beyond the second tier are resected (for example, nodesin the hepatoduodenal ligament) then this is an extendedlymphadenectomy. In the Japanese rules for surgery, 142 aresection is regarded as curative if all evidence of cancer isremoved (R0). A resection is absolute curative if at least onetier of nodes beyond those affected is removed (for example,D2 lymphadenectomyfor N0 or N1 cancer). A resection of onlythe rst tier of nodes is a D1 or limited lymphadenectomy andthis has historically been the level of resection achieved by themajority of surgeons in the West. Overall ve year survivalrates are not helpful for comparing surgical results. Compari-son of stage dependant survival rates for Japanese and West-

ern series show signicantly poorer results in the West.198

However, better results with more extensive lymph noderesection are partly due to more accurate pathological stagingof cancers (stage migration factor) and cannot be attributed tothe effects of surgery alone. In an attempt to emulate theJapanese experience, some specialised Western surgeons haveachieved similar survival rates with D2 lymphadenectomy atleast in the earlier stages of the disease. 53 202 The advantage of D2 resection appears mainly conned to stages II and IIIa. 203 A proportion of patients with N2 disease are cured by D2lymphadenectomy. This of course makes the assumption thatthey would not have stood a chance of cure with a lesserprocedure. 204 205

There are no Japanese randomised studies comparing D1and D2 resections. There are now two completed multicentretrials in the West. Neither the MRC trial nor the Dutch trialhave demonstrated a survival benet for D2 over D1 resectionfor resectable gastric cancer. 206 207 Mortality was signicantlyhigher for D2 resection in both trials, particularly when thedistal pancreas and spleen were excised as part of the lymphnode clearance. While there has been criticism of these trials,they are likelyto be representative of thelimitations of currentgastric cancer surgery in the West. However, the InternationalGastric Cancer Association consensus view in 1997 was thatpatients with curable gastric cancer should undergo a D2resection

Resection of the spleen and distal pancreasThere is increasing evidence that removal of the spleen has anadverse effect on prognosis. 208 209 The likelihood of positivesplenic hilar nodes has to be considered carefully. They arerare

in curable cancers of the distal two thirds of the stomachantrum


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oesophagus (irrespective of histology) (table 3). 218222 Three of these trials have not shown a survival advantage for preopera-tive chemoradiation but may be criticised on the basis of inad-equate chemotherapy 218 221 or radiotherapy 219 221 doses. Chemo-therapy and radiotherapy were also administered sequentiallyrather than concurrently in one trial. 219 The two positive stud-ies used chemoradiation protocols incorporating cisplatin and5-FU, with concurrent 40 or 45 Gy radiotherapy. A meta-analysis of the ve trials showed an overall improvement inthree year survival from 22% with surgery alone to 31% withpreoperative chemoradiation. The odds ratio for survival infavour of chemoradiation was 1.62 (95% CI 1.172.26).Current interest is focusing on the development of moreeffective combination regimens using newer chemotherapeu-tic agents such as the taxanes together with cisplatin and5-FU, administering continuous low doses of cytotoxic agentsthroughout radiotherapy, and delivering radiotherapy in

hyperfractionated twice daily schedules.

Definitive chemoradiation for localised SCCSCC typically presents in the proximal oesophagus and there-fore represents a greater surgical challenge than the typical ACA of the lower third. Furthermore, patients often present atan advanced age, and may be poor surgical candidates. Innon-randomised comparisons concurrent chemoradiation hasproduced pathological complete response rates consistentlyabove 20% in those who went on to have subsequent surgery(table 3). The median survival for patients treated withchemoradiation is similar to those treated with surgery alone.Chemoradiation and surgery thus appear equivalent modali-ties in SCC of the proximal oesophagus.

Gastric and oesophagogastric junction cancer Adjuvant chemotherapyThe rationale that postoperative chemotherapy may improvelocal and systemic control and ultimately survival has beenunder investigation for 25 years. A meta analysis of randomised trials has failed to show a benet for chemo-therapy over surgery alone (odds ratio 0.88 (95% CI 0.781.08)). 227 However, subsequent inclusion of a further twostudies did suggest advantage, although the exclusion of astrongly positive study would have suggested no benet. 228 A recent updated meta-analysis including recent randomisedtrials, suggests a small survival advantage with an odds ratiofor death in the treated group of 0.80 (95% CI 0.670.97) anda relative risk of 0.94 (0.881.01). 229 None the less, there

remains insufcient evidence to indicate that adjuvantchemotherapy is standard treatment and inclusion of thesepatients in clinical trials should continue, particularly withmore effective drug regimens.

Adjuvant intraperitoneal chemotherapy A small randomised study reported improved survival afterintraperitoneal administration of mitomycin C absorbed acti- vated charcoal after gastrectomy in T3/4 tumours. 230 However, when repeated in a randomised multicentre trial this result was not reproduced. 231 Intraperitoneal chemotherapy(cisplatin/5-FU) may alter the intraperitoneal failure patternand this may enhance outcome after preoperative systemicchemotherapy. In a non-randomised trial, intraperitonealchemotherapy post resection following neoadjuvant chemo-therapy decreased recurrence rates and improved survivalcompared with controls. 232 Similar results have been reported

in a randomised study with the effect most marked in stage IIIcancers. 233 This approach requires further evaluation andremains investigational.

Neoadjuvant chemotherapy Although a number of non-randomised studies have sug-gested a benet with improved survival compared withhistorical controls, 234237 randomised trial evidence is notsupportive. A Korean randomised trial comparing preopera-tive cisplatinum, etoposide, and 5-FU with surgery alonefailed to show a survival benet although resectability wasimproved. 238 A recently reported randomised study of preop-erative FAMTX (5 FU, adriamycin, and methotrexate)compared with surgery alone in 56 patients found no benet with chemotherapy. 239

Ongoing randomised studies with more effective regimens

need to be completed to dene the role of neoadjuvantchemotherapy.

Adjuvant chemoradiotherapyThe role of postoperative chemoradiotherapy in gastric cancerhas recently been evaluated in a randomised trial involving603 patients. 240 At 3.3 years median follow up there was a dis-ease free and overall survival advantage for the treated group.This approach needs further evaluation to determine whetherthis early benet is durable.

PALLIATIVE TREATMENTThe high proportion of patients presenting with advanced dis-ease highlights the fundamental importance of palliative

Table 3 Trials of neoadjuvant chemoradiation followed by surgery in oesophageal cancer

Tria l Treatment arm(s)No of patients Histology and stage

No completeresections/Nooperations

Path CR rate

Survival (median unlessotherwise stated)

Poplin223 Cisplatin/5-FU/RT 113 Squamous stage IIII 32/71 16% 12 monthsForastiere224 Cisplatin/vinblastine/5-FU/RT 43 Squamous and adeno stage IIII 36/41 23% >26 monthsGray225 Paclitaxel/ Carboplatin/5-FU/RT 73 Squamous and adeno stage IIII 56/59 54% 24 monthsStahl226 Cisplatin/5-FU/leucovorin/RT 25 Squamous and adeno stage IIIII 16/19 40% >16 monthsNygaard218 Cisplatin/ bleomycin 50 Squamous stage III NR NR 8 months

RT 48 11monthsCisplatin/bleomycin/RT 47 9 monthsSurgery al

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Guidelines for the Management of Oesophageal and Gastric Cancer

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