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Chapter

1CANCER OF THE ESOPHAGUS

Rajneesh Kumar, Sujoy Pal, and TK Chattopadhyay

1.1 INTRODUCTIONEsophageal cancer is an important cause of can-cer related death in old age. Dysphagia, which isthe predominant symptom, significantly affects thequality of life of the patients. Therefore, palliationof the disease is as important as the treatment forcure.More than two decades ago, in a classic review,

Earlam and Cunha–Melo[1] noted that of every100 patients with esophageal carcinoma, 58 willbe explored, 39 will have the tumor resected, and13 will die in hospital. Of the 26 patients leavinghospital with the tumor excised, 18 will survive for1 year, 9 for 2 years, and 4 for 5 years. While thisdismal prognosis may not be true any longer, nosinglemodality of treatment has been proven as thegold standard even today. Hence the current focusis on early detection and multimodality treatmentfor achieving better results.

1.2 EPIDEMIOLOGY

1.2.1 Incidence and Prevalence

Both squamous cell and adenocarcinoma com-monly affect the esophagus.Worldwide, squamouscell carcinoma (SCC) has been the most commonsubtype. However, cancer incidence trends showan overall decrease in SCC, whereas the incidence

of adenocarcinoma has been increasing steadilyin the West.[2, 3] In USA, adenocarcinoma is themost common subtype of esophageal carcinomaat present.[4]

Certain geographic regions have a high inci-dence of esophageal carcinoma (Table 1.1). Theso-called ‘Asian esophageal cancer belt’ stretchesfrom Turkey, east of the Caspian Sea throughnorthern Iran, northern Afghanistan, southernregions of the former USSR such as Turk-menistan, Uzbekistan, Tajikistan; to India, China,andMongolia.[5] Other regionswith high incidenceare certain parts of Africa (e.g., Transkei region ofSouth Africa) and South America. The incidenceof esophageal cancer relative to other cancers inIndia is shown in Table 1.2. Men are more affectedthan women, probably due to the high prevalenceof risk factors like smoking and alcohol intake inmales.

1.2.2 Dysplasia/Carcinoma Sequence

Various lesions of the esophageal epitheliumare precursors to cancer. They include chronicesophagitis, atrophy, dysplasia, papilloma, andcarcinoma in situ.[6, 7] Esophageal carcinoma maydevelop at the site of these precursors. Theselesions are prevalent in high risk populations, and

3

4 Chapter 1 / CANCER OF THE ESOPHAGUS

fyTABLE 1.1 IARC (International Agency forResearch on Cancer) (WHO):Incidence of esophageal cancerworld over (year 2000)

Country ASR (per 100,000 population)

Kenya 21.8Malawi 38.6Botswana 37.2Lesotho 37.2South Africa 16.3China 24.5Mongolia 24.4Iran 24.0Turkmenistan 26.4India 7.5World (overall) 10.7

ASR = age-standardized rate

fyTABLE 1.2 IARC (International Agency forResearch on Cancer) (WHO):Incidence of esophageal and othercancers in India (year 2000)

Site of cancer ASR (per 100,000population)

Males Females

Oral 12.8 7.4Pharynx 9.5 1.8Esophagus 7.5 5.1Lung 9.0 1.9Larynx 6.2 0.7Prostate 4.5 –Stomach 5.6 2.8Colorectum 4.7 3.2Breast – 19.1Cervix – 30.6Ovary – 4.8

ASR = age-standardized rate

may be present alongside invasive carcinoma inesophagectomy specimens.

1.2.3 Risk Factors and Associations

1.2.3.1 Alcohol and tobacco

Alcohol and tobacco are well established etiologicfactors for esophageal carcinoma, and, in fact, areassociated with most cancers of the upper aerodi-gestive tract.[8] Several carcinogens are present incigarette smoke. These include nitrosamines andpolynuclear aromatic hydrocarbons such as ben-zpyrene. Pipe and cigar smoking is found to beworse as a risk association.Black tobacco and handrolled cigarette smoking has a higher relative risk.The risk increases with the number of cigarettesand the duration of smoking.For alcoholic drinks, the risk varies with the

type of drink consumed. It is least with beerand intermediate with wine. Alcohol and tobaccoexert a synergistic effect. They potentiate eachother, leading to a field within the upper aero-digestive tract where the epithelium is exposed tocarcinogens, and is thus prone to develop multipletumors. This explains the high risk of synchronousand metachronous carcinoma in the upperaerodigestive tract in patients with esophagealcancer.[9]

1.2.3.2 Dietary carcinogensN-nitroso compounds like nitrosamines are knowndietary carcinogens, and are found in high levelsin the diet in high incidence regions like theLinxian Province of China.[10] Cured, smoked,or sun-dried salted meat, fish, or vegetables arerich in such carcinogens. In Kashmir, Khurooand colleagues[11] found that the high risk dietcontained substantial amounts of N-nitroso com-pounds in foods such as salt, tea, dried fish, certainvegetables, and red chilies.

1.2.3.3 Nutritional deficienciesCertain micronutrient and vitamin deficiencies areassociated with esophageal cancer. Diets deficient

Tropical Hepatogastroenterology

EPIDEMIOLOGY 5

in vitamins A, C, E, niacin, riboflavin, mag-nesium, selenium, and zinc, diets rich in pro-cessed and starchy foods, and diets poor in freshfruits and vegetables are associated with increasedrisks of esophageal carcinoma.[12] In the Transkeiregion, pellagra used to be very prevalent. Patientswith pellagra had intensely inflamed esophagealmucosa, which placed these patients at a very highrisk for developing esophageal carcinoma.[13]

1.2.3.4 Environmental factors and pollutants

The soil theory gained credence from studiesdone in Transkei, South Africa.[14] There appearsto be an inverse correlation between mortalityfrom esophageal cancer and the soil content ofmolybdenum, manganese, zinc, magnesium, sili-con, nickel, iron, bromine, iodine, chlorine, potas-sium, sodium, phosphorus, and bicarbonate. Howthese substances affect the esophageal epitheliumis not known. Molybdenum is a cofactor of theenzyme nitrate reductase which affects nitrite andnitrate content in plants. Petroleum contamina-tion of water and occupational exposure of metaldust such as chromium, chromates, berylliummayincrease the risks of esophageal cancer.[15] Vul-canization workers, plumbers, and pipe fittershave been identified in some studies as high riskgroups.[16]

1.2.3.5 Infections

Human papilloma virus (HPV), especially types16 and 18, are implicated in the pathogenesis ofcancers developing in several squamous epithe-lia including cervix, vulva, larynx, and skin. HPVDNA sequence has been found in both benign andmalignant esophageal conditions.[17] Fungi havebeen implicated as agents especially from studiesin China. Of the various fungal infections of theesophagus, candida is themost common. Common

fungi such as Fusarium, Alternaria, Aspergillus,andCladosporium have been found contaminatingthe grains.[18] These can reduce nitrates to nitrites,and can also decompose proteins and promote theformation of nitrosamines.

1.2.3.6 Chronic esophageal irritation

Chronic thermal and mechanical irritation due todietary factors is frequently associated with therisk of esophageal cancer. Hot tea is consumed inlarge amounts in high incidence regions of Iran.[19]

Drinking of the plant extract ‘mate’ has a frequentassociation in high incidence regions of SouthAmerica.[20] Hot rice intake has been implicatedin China.[21]

In Iran and theMiddle East, food grains containfibrous material from contaminating seeds of com-mon Mediterranean grass. This fibrous materialhas carcinogenic properties.Spicy and improperly chewed foods have

been implicated in the risk of esophagealcarcinoma.

1.2.3.7 Achalasia cardia

Patients with long-standing achalasia are at highrisk of esophageal carcinoma, most likely fromchronic stasis and inflammation. The preva-lence of esophageal carcinoma in various stud-ies of long-standing achalasia varies from 0% to8.6%.[22–24] Recently, histological mapping of theresected esophageal specimens has demonstratedmarked hyperplastic changes of stratified squa-mous epithelium and multiple foci of dysplasticchanges.[25] In recent studies, the changes in p53,p16, p21, epidermal growth factor immunoreactiv-ity, marked squamous hyperplasia, and increasednumbers of CD3+ cells have been found in the atrisk epithelium.[26] The tumor usually occurs in thedilated middle third part of the esophagus. Most

Part I / Esophagus


of these are squamous cell carcinoma. However,reflux following myotomy may cause Barrett’sesophagus and adenocarcinoma. The diagnosisis usually made late, and the prognosis is poor.Patientswith achalasia for over 15–20 years shouldundergo surveillance with 6-monthly endoscopyand biopsy.[27]

Some cases of carcinoma may clinically mimicachalasia; this presentation is termed pseudoacha-lasia. Liu and colleagues[28] recently studied pseu-doachalasia. They found that most cases weredue to neoplastic infiltration of the myentericplexus, and a few represent a paraneoplastic syn-drome due to a distant neoplasm (e.g., lungcarcinoma).

1.2.3.8 Corrosive strictures

Between 1% and 7% of patients with esophagealcarcinoma have a history of corrosive intake. Car-cinoma develops after about 40 years.[29] Men aremore frequently affected than females, and thecarcinomausually develops at the region of the cor-rosive stricture. The mechanism is chronic inflam-mation associated with the stricture. Appelqvistand Salmo[30] noted a better prognosis for these‘scar’ carcinomas and proposed that this wasbecause of younger age, early obstructive symp-toms, and scar tissuewhich prevents early dissemi-nation of the tumor.[31] This risk of latemalignancyhas led some surgeons to perform esophagectomyin patients with severe corrosive injury of theesophagus.[32]

1.2.3.9 Esophageal diverticula

Malignant transformation in chronic Zenker’sdiverticulum is rare, and a very small number ofcases have been reported. A large Mayo clinicseries of 961 Zenker’s diverticulum had a 0.3%prevalence of carcinoma.[33]

1.2.3.10 Others

Irradiation and chemotherapy have been impli-cated as causing esophageal carcinoma in anec-dotal reports. Endoscopic sclerotherapy has beenassociated as an etiologic agent. However, it isbelieved that this relationship is only due to coex-isting factors.A previous history of gastrectomy for benign

diseases is found in 0.7%–10.4% of patients withsquamous cell carcinoma of the esophagus.[34] Itis difficult to separate this risk from confoundingfactors and formulate any definite guidelines forsurveillance.Plummer–Vinson syndrome (Paterson–Kelly

syndrome) is characterized by iron deficiency ane-mia, atrophy of oral, pharyngeal and esophagealmucosa, and esophageal webs. These patientsare predisposed to developing carcinoma in theupper digestive tract.[35] The risk of developingcarcinoma is about 10%.Tylosis is a rare autosomal dominant disease

characterized by hyperkeratosis of the palms andsoles. Up to 95% of these patients develop squa-mous cell carcinoma by the age of 65 years.[36]

Celiac disease and scleroderma have been asso-ciated with the development of squamous cell andadenocarcinoma respectively, but the relationshipis thought to be secondary.Genetic predisposition has a relatively minor

role in esophageal carcinoma. In China a few fam-ilies have been identified with a strong geneticsusceptibility of developing esophageal carci-noma.[37]

1.2.3.11 Barrett’s metaplasia

Barrett’s intestinal metaplasia is protectiveresponse to acid reflux in the esophagus.Endoscopically it can be divided into three types:(a) long segment Barrett’s where the metaplastic


PATHOLOGY 7

epithelium extends for more than 3 cm proximalto the gastroesophageal junction; (b) short seg-ment Barrett’s where it is limited to within 3 cmof the cardia; and (c) gastric cardia metaplasia,which is restricted to the region of the cardiaonly. The prevalence of Barrett’s is 5%–15% inpatients undergoing endoscopy for symptoms ofreflux.[38] The risk of adenocarcinoma in longsegment Barrett’s metaplasia is 0.5% annually.[39]

The magnitude of risk in short segment Barrett’sis less.[40] The risk is even lower in patients withgastric cardia metaplasia. Though no high riskgroup can be clearly identified in the patients withBarrett’s metaplasia, some characteristics mayhelp in selecting patients at higher risk for devel-oping carcinoma. These include obesity, whitemales, young age, ulceration, and long-standingdisease.[41] The presence ofH.pylorihas an inverserelationship with the development of esophagealadenocarcinoma.

1.2.3.12 Genetics of esophageal carcinoma

Several genetic mutations have been identifiedwhich are associated with esophageal carcinoma(Table 1.3). Epidermal growth factor receptor(EGFr) gene is overexpressed in approximately30%–80% of cases. TGF-alpha (transforminggrowth factor alpha) is expressed in 40%of tumors.

fyTABLE 1.3 Expression of genetic mutations inesophageal carcinoma

Tumor suppressor genes Oncogenes Others

FHIT EGFr SurvivinRb erbB2 VEGFp53 Cyclin D1 E-cadherinp16 CateninsP14 Ki-67Telomerase Interleukin-1

Note: For details of abbreviations see text

It binds to EGFr to stimulate growth. The overex-pression of the ErbB2 and cyclin D1 genes hasbeen observed in 30%–50% and 40%–60% ofcases of esophageal carcinoma respectively. Rasmutations are uncommonly foundwith esophagealcarcinoma[42]

Fragile histidine triad (FHIT) gene mutationshave been found in 60%–100% of esophageal can-cer as well as in Barrett’s metaplasia. This appearsto be a relatively early event in carcinogenesis inBarrett’s epithelium.[43] Retinoblastoma (Rb) geneproduct is a critical mediator of cell cycle arrestafter DNA damage, and its mutations have beenfound in 20%–40% of the tumors. The p53 geneproduct regulates cell cycle, DNA repair, apop-tosis, and controls the cell cycle. P53 mutationsare associated with poorly differentiated tumorsand poor survival in patients with esophageal ade-nocarcinoma.[44] P16 gene mutations have beenidentified in about 20% of esophageal squamouscell carcinoma.Esophageal carcinoma is not a vascular tumor,

but we have found VEGF (vascular endothelialgrowth factor) expression to correlate with lymphnode metastasis and patient survival.[45]

In a recent review, the principal genes impli-cated in the progression from Barrett’s metaplasiato dysplasia and adenocarcinoma are the loss ofp16 and p53 gene expression, increase in cyclinD1 expression, induction of aneuploidy, and lossof Rb, DCC (deleted in colon cancer), and APC(adenomatous polyposis coli) gene chromosomalloci.[46]

1.3 PATHOLOGY

1.3.1 Squamous Cell Carcinoma

Worldwide, this is the most common form ofesophageal carcinoma. Most tumors (55%) arelocated in the middle third of the esophagus.[47]

Part I / Esophagus


Thirty percent are located in the lower third, and15% in the upper third of the esophagus.As previously mentioned, there is some

evidence for a dysplasia—carcinoma-in-situ—invasive carcinoma sequence in esophageal carci-noma. Screening methods are designed to identifythese preinvasive lesions. It has been estimated thatcarcinoma-in-situ takes 3–4 years to develop intoinvasive carcinoma.[48]

Grossly, the lesion may vary from a subtlemucosal abnormality to a macroscopically obvi-ous lesion that may be exophytic or endophytic.Exophytic variants include fungating, polypoidal,or plaque-like tumors. Endophytic tumors are infil-trative. Microscopically, the tumor may vary froma well differentiated squamous type to poorlydifferentiated pleomorphic cells.The tumor spreads by transmural invasion

through various layers of the esophageal wall.Since there is no serosa, mediastinal structureslike the recurrent laryngeal nerve, aorta, trachea,and others are involved early. Invasion of thetracheobronchial tree is the most common, andmay lead to the formation of a tracheoesophagealfistula.Lymphatic spread occurs to the nodes of

the mediastinum, neck, and upper abdomen.Twenty percent to thirty percent of lower thirdtumors spread to the superior mediastinal nodes,and the same numbers of upper third tumorsinvolve abdominal nodes.[49, 50] Transmural tumor

fyTABLE 1.4 Transmural extension oftumor: Correlation with nodalmetastases[51–53]

Tumor extent Nodal spread

Mucosal 3%Submucosal 30%Muscularis propria 60%Transmural Nearly 100%

spread correlates with lymphatic dissemination(Table 1.4).[51–53]

The esophagus is rich in submucosal lymphat-ics, and longitudinal spread along the esophagusmay give rise to tumor deposits in the submucosaas far away as 15 cm from the main tumor.[54, 55]

This fact itself is sufficient justification for atotal esophagectomy as opposed to a subtotalesophagectomy.Blood borne metastasis may involve the lung,

liver, bone, and kidney.Lymph node micrometastases do not signifi-

cantly affect survival in patients with esophagealcarcinoma,[56] but bonemicrometastases do. In onestudy, up to 90% of resected ribs were positive formarrowmicrometastases, and this factor correlatedwith prognosis on multivariate analysis.[57]

1.3.2 Adenocarcinoma

Most adenocarcinomas arise in the background ofBarrett’s metaplasia. However, this may not beidentifiable in a large tumor. Often, it is difficult toseparate gastric carcinoma froman esophageal car-cinoma at the gastroesophageal junction. In a bid toseparate these tumors, Siewert proposed a classifi-cation that is now commonly accepted.[58, 59] Ade-nocarcinomas of the gastroesophageal junction aredefined as tumors whose centers lie within 5 cmof the anatomic cardia. They can be subclassifiedas:

Type I – Adenocarcinoma of the distal esoph-agus, located at least 1 cm above thecardia and usually arising from an areaof Barrett’s metaplasia.

Type II – Tumors arising from cardiac epithe-lium or from intestinal metaplasia at thegastric cardia.

Type III – Subcardial gastric carcinoma.


SYMPTOMS AND SIGNS 9

The anatomic location of the tumor cen-ter determines the assignment of subcategory.Ichikura and colleagues[60] have defined type IItumors (cardia carcinoma) as adenocarcinomaswith their epicenter between 1 cm proximal and2 cm distal to the esophagogastric junction.Lower esophageal adenocarcinoma spreads

both to mediastinal as well as abdominal nodes.Adenocarcinoma of the cardia and subcardialstomach spreads predominantly to the celiac,splenic hilar, and periaortic nodes.[61]

1.3.3 Uncommon Subtypes

Verrucous carcinoma is a superficial, slow grow-ing tumor. Spindle cell carcinoma is a poly-poidal tumor which tends not to infiltrate deeply.Mucoepidermoid and adenoid cystic carcinomaare aggressive tumors, and nodal metastases arecommon.Small cell carcinomas are usually large exo-

phytic masses. These are often associated withsquamous differentiation. Secretion of ACTH,hypercalcemia, and SIADH may occur as associ-ated paraneoplastic syndromes. Overall these areaggressive tumors with poor survival.

1.3.4 Prognostic Factors

The most important prognostic factor is the TNMstage. The depth of tumor infiltration, and the pres-ence or absence of nodal and distant metastasis areprimary determinants of prognosis. Recently, thenumber of involved nodes has been identified as animportant factor. Involvement of more than fournodes is associated with a poorer survival.[62, 63]

A lymph node positivity ratio of more than 0.1is a poor prognostic factor.[64] Gross morphologyand tumor type are not independent prognosticfactors. Some tumors such as verrucous carci-noma and spindle cell carcinoma carry a better

outcome. While length of the tumor has a lesserbearing on prognosis than the TNM stage, a recentseries found that the increasing length of the tumorbeyond 5 cm worsens the prognosis.[65]

It was previously thought that adenocarcinomahas a worse prognosis. However, this appears tobe a function of a more advanced stage at pre-sentation. The long-term prognosis is otherwisesimilar to squamous cell carcinoma.[66] Osugi andcolleagues[67] showed that vascular and lymphaticinvasionworsen the prognosis. Advanced age is nolonger considered a poor prognostic factor. Elderlypatients, if properly selected, have results as goodas younger patients.[68] Perioperative blood trans-fusion may worsen the prognosis.[69]

Lately, improved molecular techniques haveidentified newer prognostic markers. AlthoughDNA aneuploidy (flow cytometry), p53 mutation,elevated EGF, EGFr, and TGF-alpha have corre-latedwithworse outcome,more evidence is neededfor the clinical relevance of these factors.

1.4 SYMPTOMS AND SIGNS

Although esophageal carcinoma is typically a dis-ease of old age (sixth to seventh decade), in ourcountry one frequently encounters much youngerpatients. In fact the youngest patient in our expe-rience was a 23 year old lady. The duration ofsymptoms is typically short, as opposed to benignesophageal disorders. Symptom duration longerthan 6 months indicates an advanced tumor.[70]

Dysphagia is the cardinal symptom which, ifpresent in an old individual, should be consid-ered suspicious of an esophageal cancer. Dys-phagia, initially to solids and later to liquids, ispresent in 90% of cases, and occurs once theluminal compromise is at least two-thirds. Theabsence of serosa in most of the esophagus enablestumors to expand into surrounding tissues beforeluminal stenosis becomes symptomatic. Hence it

Part I / Esophagus


follows that most patients with esophageal carci-noma present with an advanced malignancy. Onlyin regions of the world where screening has beensuccessfully employed (e.g., China), early lesionsare detected in substantial numbers.Anorexia and weight loss are frequently asso-

ciated symptoms, and are present in up to 75%of the patients. Other symptoms like odynopha-gia, regurgitation, and cough may be present.A preceding history of heartburn may be theonly indicator of reflux in Barrett’s esophaguswith malignant change. Sinister symptoms areweight loss (>10%), hoarseness (from recur-rent laryngeal nerve palsy), cough on swallowing(from an esophagorespiratory fistula), and backor chest pain (indicating invasion of mediastinalstructures).[71] Cough may be due to esophago-respiratoryfistula or aspiration due to anobstructedesophagus. Esophagorespiratory fistulae occur inabout 5% of the cases, and are essentially incur-able, with a short survival of 1.5 to 4 months.[72]

Significant cough in the absence of either of theabove may occur in chronic smokers, and tuber-culosis should be kept in mind in these poorlynourished individuals.Hematemesis is an uncommon symptom.

Although it is usually due to tumor erosion andulceration, massive exsanguinating hemorrhagecan occur due to an esophagoaortic fistula fromtumor infiltration of the aorta.Clinical features due to metastasis may be bone

pains, lump in the upper abdomen due to a lymphnodal mass or hepatic metastasis, or a lump in theneck due to cervical nodal metastasis.Clinical examination may not reveal disease-

specific findings in most patients. However, it isimportant to assess the nutritional status of thepatient by recording the body weight, triceps skin-fold thickness, pedal edema, and pallor. Since thesepatients are frequently chronic smokers, clinicalexamination should look for features of chronic

obstructive airway disease and pulmonary infec-tions. Breath holding time is a useful bedside testto assess the pulmonary reserve. Details of car-diopulmonary disease, diabetes, and tuberculosisshould be carefully sought.Assessment for tobacco and alcohol abuse is

important. In the Indian subcontinent, chewableformsof tobacco are quite commonly used.Carefuloral and pharyngeal examinationmay occasionallyreveal synchronous tumors.

1.5 DIAGNOSTIC INVESTIGATIONS

Laboratory investigations usually show anemiaand hypoalbuminemia. Serum alkaline phos-phatase may be elevated in patients with liver orbone metastasis. Hypercalcemia may occur as aparaneoplastic syndrome in squamous cell car-cinoma. It is due to a parathyroid hormone-likepeptide produced by the tumor. Hypercalcemiamay also be due to extensive bone metastasis. Therare small cell carcinoma is associated with otherparaneoplastic syndromes.

1.5.1 Barium Swallow

Contrast radiography using barium sulfate givesvaluable information. It shows the level ofesophageal obstruction, its nature, proximalesophageal dilatation (usually not marked due tothe short duration of illness), and the distal extentof the lesion particularlywith regard to the involve-ment of the gastroesophageal junction and thestomach (Fig. 1.1). Barium swallow is particularlyuseful in defining the presence of an esophagores-piratory fistula. Water soluble contrast agents like‘gastrografin’ should not be used because of thepotential of causing lung damage due to its hyper-osmolarity. Esophageal axis deviation on bariumswallow predicts an advanced, unresectable tumor(Table 1.5).[73, 74]


SCREENING 11

FIGURE 1.1Barium swallow showing irregular narrowing withshouldering in the distal esophagus, typical of esophagealcarcinoma.

fyTABLE 1.5 Constituents of axis deviation fy

• Tortuosity of the esophageal axis proximal to thetumor

• Angulation of the esophageal axis• Deviation of the esophageal axis

– Above and below the tumor– Of the tumor itself– Abnormality of the distance of the tumor from

the spine

Barium swallow was the cornerstone of diag-nosis before the advent of endoscopy. Today, wecontinue to advocate this simple and cheap inves-tigation before endoscopy because (i) it servesas a roadmap to the endoscopist, and often forthe surgeon who does not see the tumor himselfbefore surgery; (ii) its use in defining an esophago-respiratory fistula is unquestionable; (iii) axis

deviation is an important feature which predictsunresectability.[75, 76]

1.5.2 Endoscopy

Fiberoptic endoscopy has now become the goldstandard for the diagnosis of esophageal carci-noma. At least six biopsy samples from non-necrotic tumor areas are required to get the bestpossible yield nearing 100%. Occasionally, dilata-tion of the tumor may be required before accessbecomes adequate for biopsies. Nondiagnosticbiopsies may sometimes be an indication to takea biopsy with a large angled cup forceps through arigid esophagoscope.While brush cytology should complement the

yield of biopsy, it has not been used extensively inthe diagnosis of carcinoma esophagus.In addition to biopsy, endoscopy can be used

to assess the degree of obstruction caused by thetumor, the proximal and distal extent (in passablelesions), the presence of a second synchronoustumor, and to place a nasogastric tube for feed-ing. The location of the tumor is measured incentimeters from the incisors. The distal extent ofthe tumor is particularly important in adenocarci-noma at the gastroesophageal junction, where theextent of stomach involvement will influence itsuse as the conduit of choice after esophagectomy.When this cannot be assessed by endoscopy, thisshould be seen by barium swallow.

1.6 SCREENING

Most cases of esophageal carcinoma are detectedin advanced stages, hence the long-term resultsof therapy are poor. Detecting esophageal car-cinoma early is an effective way of improvingsurvival. In these early cancers the long-term sur-vival sometimes exceeds 90%. Screening maybe useful in high risk populations with diseases

Part I / Esophagus


like upper aerodigestive cancers, gluten enteropa-thy, Plummer-Vinson disease, achalasia, andmalesover the age of 50 years with a history of heavyabuse of cigarettes or alcohol.

1.6.1 Screening for Squamous CellCarcinoma

Screening for squamous cell carcinoma has beeneffective only in high-incidence regions of theworld. One such region is the Linxian provinceof China, where nonendoscopic screening usingabrasive balloon cytology has been successfullyused to detect early carcinoma.[77] Various modal-ities which have been used for screening are asfollows:

1.6.1.1 Endoscopy

Early lesions may appear as mild irregularity,erythema, or ulceration, or they may be missedaltogether on routine screening endoscopy.Chromoendoscopy increases the probability of

identifying dysplasia. Chromoendoscopy refers tothe vital staining of tissues with topical dyes toimprove localization during endoscopy. The dyesused are Lugol’s iodine, toluidine blue, indigocarmine, andmethylene blue. Lugol’s iodine stainsthe glycogen of the normal squamous epitheliumblack, and the biopsy should be taken from theunstained areas.[78] The other dyes are taken up byabnormal epithelium.Toluidine blue has an affinityfor staining the cellular nuclei. Unfortunately thesemay be taken up in areas of inflammation, ero-sions, and ulcerations also. Methylene blue stainsabsorptive epithelium like small intestine, colonicepithelium, and Barrett’s epithelium, but does notstain nonabsorptive epithelium such as squamousor gastric epithelium. Compared to nondirectedbiopsy, methylene blue increases the yield forBarrett’s epithelium.

1.6.1.2 Nonendoscopic methods

Two popular methods for screening have beendeveloped and used extensively. The mesh cov-ered balloon has been used in China and thegelatin encapsulated sponge has been evaluated inJapan.The balloon is swallowed and inflated in the

stomach with 20–30ml of air. It is gradually with-drawn through the esophagus, and after removal issmeared on a slide. The sponge sampler is swal-lowed and left in the stomach for 5 minutes wherethe gelatin dissolves and the sponge expands.This is then withdrawn through the esophagus.After removal it is shaken in fluid and cytologi-cal examination is carried out after centrifugationof the fluid. The largest experience of the useof cytological screening has been in China.[79, 80]

The accuracy in symptomatic individuals is higherthan in asymptomatic individuals. Another form ofblind cytology is with a standard cytology brushinserted through a nasoesophageal tube.

1.6.2 Screening in Barrett’s Esophagus

1.6.2.1 Endoscopy

The annual risk for developing adenocarcinomain Barrett’s metaplasia is 0.5% to 1.5%.[81,82]

Endoscopy with biopsy is, therefore, required forsurveillance in patients with Barrett’s metaplasia.Biopsies should be taken from each quadrant every2 cmwithin theBarrett’s epithelium. Jumbobiopsyforceps and brush cytology increase the yield ofpositive diagnosis of dysplasia or cancer.In the absence of dysplasia, screening should be

done once in 2–3 years.[81]

The presence of low-grade dysplasia war-rants treatment with a high dose course of anti-secretory drugs and repeat biopsy. Endoscopyshould be done half-yearly for one year, and thenyearly.


STAGING: IMAGING AND OTHER METHODS 13

fyTABLE 1.6 Techniques used to increase theefficacy of surveillance

• Magnification endoscopy• Chromoendoscopy (e.g., by methylene blue)• Brush cytology• Optical coherence tomography• Laser induced fluorescence spectroscopy• Flow cytometry (to measure the DNA content)• P53 immunohistochemistry• Proton magnetic resonance spectroscopy (of esophageal

biopsies)

In high-grade dysplasia the risk of adenocar-cinoma is 27% over 3 years.[83] Current rec-ommended treatment for high-grade dysplasia isesophagectomy. Less often, authors recommendintensive endoscopic surveillance.[84]

1.6.2.2 Other modalities

Several techniques have been used to increase theefficacy of surveillance (Table 1.6).Methylene blue is particularly used in screening

for Barrett’s epithelium.

1.7 STAGING: IMAGING AND OTHERMETHODS

The American Joint Committee on cancer stag-ing system is based on the primary tumor, nodalinvolvement, and distant metastasis (Table 1.7).[85]

The tumor size and spread cannot be evaluatedclinically, and staging depends entirely upon imag-ing. This staging system has been most applicableto upper andmiddle third squamous cell carcinomaas opposed to the lower third adenocarcinoma.

1.7.1 Chest X-Ray

Conventional posteroanterior chest radiographsshould be done in all patients of carcinoma

esophagus. Findings may include lung metasta-sis, changes of chronic obstructive airway dis-ease, pneumonitis, mediastinal widening, andesophageal air-fluid level. The presence of pul-monary metastasis precludes long-term survival,hence unnecessary expensive staging investiga-tions are avoided.

fyTABLE 1.7 AJCC (1997) TNM staging foresophageal carcinoma

T (Primary tumor)

• Tx : Tumor cannot be assessed

• T0: No evidence of primary tumor

• Tis : High-grade dysplasia

• T1: Tumor invades lamina propria, muscularis mucosa, orsubmucosa. Does not breach submucosa

• T2: Tumor invades into but beyond muscularis propria

• T3: Tumor invades periesophageal adventia but does notinvade the adjacent organs

• T4: Tumor invades adjacent structures

N (Regional nodal metastasis)

• Nx : Nodal status not assessable

• N0: No nodes involved

• N1: Regional nodes involved

M (Nonregional nodes and distant metastasis)

• Mx : Distant metastasis not assessable

• M1a*: Upper thoracic tumors metastatic to cervicalnodes. Lower thoracic tumors metastatic to celiac nodes

• M1b: Upper and lower thoracic tumors metastatic toother nonregional nodes or distant sites. Middle thoracictumors metastatic to any nonregional nodes or distantmetastasis

Stage grouping

Stage 0 TisN0M0

Stage I T1N0M0

Stage IIa T2N0M0, T3N0M0

Stage IIb T1N1M0, T2N1M0

Stage III T3N1M0, T4N0M0, T4N1M0

Stage IV Any T, any N, M1a or M1b

∗No M1a category exists for middle thoracic tumors.Any non-regional nodal metastasis has the same prognosis as distantmetastasis

Part I / Esophagus


1.7.2 Bronchoscopy

Bronchoscopy is mandatory in upper and middlethird tumors due to their proximity to the majorairways. Displacement of the airway does not pre-clude resection, but is a significant finding for thesurgeon.[86] Early features of involvement includemucosal edema or elevation with contact bleeding.Direct infiltration of the trachea or bronchi con-traindicates resection.Widening, of the carinamaybe because of the tumor, or, more likely, because ofsubcarinal nodes. Transcarinal fine needle aspira-tion cytology (FNAC) can be used to confirmnodalmetastasis, but is usually unnecessary.

1.7.3 Computed Tomography (CT Scan):Chest and Upper Abdomen

Contrast enhanced CT scan of the chest and upperabdomen has the highest accuracy for distantmetastasis (M stage), particularly lung, liver, bone,and adrenal metastasis. CT has limited value inassessing the primary tumor (T stage) and nodalinvolvement (N stage). Wall thickness more than5mm is abnormal on CT scan. Primary tumor mayappear as esophageal wall thickening or as a medi-astinal mass in advanced stages (Fig. 1.2). Lengthof the tumor may be underestimated by 2 to 3 cmby CT scan. Invasion of mediastinal structures isan important determinant of resectability and prog-nosis. Although loss of fat planes is considered acriterion of invasion, this may be lost not only dueto invasion but also due to cachexia, prior operationor radiotherapy.The cervical esophagus and gastroesophageal

junction are particularly difficult to evaluatebecause of lack of natural fat planes. Aortic inva-sion is best predicted by an angle of contact of thetumor with the aorta greater than 90◦. The overallaccuracy of prediction of invasion of mediastinalstructures is 80%–85%, but the sensitivity is as lowas 50%–55%.[86,87] Lymph nodal involvement is

FIGURE 1.2Contrast enhanced CT scan of lower chest and upperabdomen. There is a concentric wall thickening with asoft tissue mass lesion causing luminal narrowing in theesophagus (A – aorta).

diagnosed on the basis of node size larger than1 cm. However, nodal metastasis may be present innormal size nodes, and nodal enlargement may bedue to reactive hyperplasia.[88] Hence the accuracyof predicting nodal involvement is less than 60%and the sensitivity is even lower at about 30%.[89,90]

1.7.4 Magnetic Resonance Imaging

Magnetic resonance imaging (MRI) has no dis-cernable advantage over CT scan in the evaluationof esophageal carcinoma.

1.7.5 Positron Emission Tomography

Metabolically active tumor tissue takes up 18F-fluorodeoxyglucose (FDG). The uptake can be


STAGING: IMAGING AND OTHER METHODS 15

imaged by the positron emission tomography(PET). PET is most useful in picking up distantmetastasis. The accuracy for M staging is 90%,including about 10%–20% of metastasis that arenot detectable with conventional staging imag-ing.[91] PET is not of much use as far as T stagingis concerned. PET cannot differentiate adjacent N1

nodes from primary tumor; hence the accuracy forN staging is low, though variable (about 30%–40%).[92] It gives better results for distant nodes(M1a). PET may be more useful for staging afterneoadjuvant therapy.

1.7.6 Endoscopic Ultrasound

Endoscopic ultrasound (EUS) has proved highlyaccurate in T, and, to a certain extent, in Nstaging.[93] Five layers are identified (Table 1.8,Fig. 1.3).Radial (360◦ view) and linear array (100◦ for-

ward view) probes scanners are most often used.The probe frequencies most often used are 7.5 and12MHz.In a large review the accuracy for T staging

was 84%.[94] While conventional EUS can iden-tify T1 and T2 stage tumor, EUS probes of higherfrequency (20MHz) can give further definitionof the infiltration of mucosa (T1a) and submu-cosa (T1b).[90] Such information is useful whenendoscopic resection is being considered.The limitations with T staging are an

obstructing tumor, microscopic tumor invasion,

fyTABLE 1.8 Five layers of esophagus seen on EUS

1. Inner hyperechoic layer – superficial mucosa (epithe-lium and lamina propria)

2. Inner hypoechoic layer – deep mucosa (muscularismucosa)

3. Middle hyperechoic layer – submucosa4. Outer hypoechoic layer – muscularis mucosa5. Outer hypoechoic layer – periesophageal fatty

tissue

FIGURE 1.3Endoscopic ultrasound showing a large transmuralgrowth (arrow) invading into the periesophageal tissues:T4 lesion.

peritumoral inflammatory changes, and fibrosisbecause of neoadjuvant therapy.[95]

EUS is less accurate for nodal staging. Thecharacteristics associated with nodal involvementare size greater than 1 cm, hypoechogenicity,discrete margins, and rounded shape. When allfour features are present the diagnostic accu-racy is 80%.[96] However, these characteristicsare present in only 25% cases. EUS guidedFNAC can enhance the value of EUS in nodalstaging.The impact of EUS on clinical decision making

will vary depending on the local treatment policy.The usefulness is minimal if the surgery is consid-ered the preferred treatment even if the intent ispalliative.Bronchoscopic ultrasound and intra-aortic

ultrasound have been studied in staging localinvasion in esophageal carcinoma but have notbeen commonly used.[97, 98]

Part I / Esophagus


1.7.7 Bone Scan (Tc99m-LabelledDiphosphonate)

A bone scan is useful in picking up bone metas-tasis, but inflammatory lesions and fractures canbe confounding factors. It is not in routine use forstaging esophageal carcinoma.

1.7.8 Minimally Invasive Staging

Thoracoscopic and laparoscopic staging haveadded to the diagnostic accuracy of preoperativeinvestigations. Thoracoscopy is done from theright side, and the nodes between the subcla-vian vessels and the inferior pulmonary veinare sampled. Some oncologists also use medi-astinoscopy to assess mediastinal lymphadenopa-thy in esophageal cancer.Laparoscopic staging includes celiac node sam-

pling and laparoscopic ultrasound for detectingliver metastasis. Laparoscopy may be better thanEUS in abdominal staging, given the limitationsof EUS in this part. Minilaparotomy has also beenused to look for small peritoneal (subdiaphrag-matic) and hepatic surface metastasis.Minimally invasive techniques, however, have

not been used extensively in world literature andrequire to be evaluated much more thoroughlybefore being recommended. They have the advan-tage of being extremely specific, but are invasiveand require general anesthesia.Krasna et al.[99, 100] have reported an accuracy

of 94% in laparoscopy and 91% in thoracoscopyfor staging esophageal cancer.

1.7.9 Biological Staging

Nonanatomic techniques for staging esophagealcarcinoma assess genetic alterations, oncogenes,DNA content, and other prognostic determinants.The DNA content is inversely related to survival.Similarly, several genetic alterations are found in

relation to esophageal carcinoma. Biological stag-ing refers to process of prognosticating the tumorbehavior based on these alterations. In the futurethe genetic and molecular characteristics of thetumor will help in stratifying the patients in orderto individualize therapy.

1.7.10 Pathologic Staging

Pathologic stage is the clinical stage modifiedby additional information acquired by surgeryand pathologic examination of the specimen. Foresophageal cancer the pathologic and clinical stag-ing is similar.Overall, staging techniques will vary accord-

ing to protocols adopted by the treating physicians(Table 1.9).

1.8 TREATMENT

1.8.1 Preparation before Surgery forOperable Patients

Most patients are cachectic due to dysphagia,anorexia, and recurrent chest infections. Lowserum albumin and body weight correlate with apoor surgical outcome.[101] The surgeon shouldattempt to achieve a serum albumin more than3.5 gm% if possible, by enteral rather than par-enteral nutrition. If the patient is unable to eatsufficiently, he needs a nasogastric tube, or even

fyTABLE 1.9 Our approach to staging

We get a barium swallow in all patients with dysphagia.Cancer is confirmed with endoscopy and biopsy. The tumoris staged with a contrast enhanced CT scan of the chest andupper abdomen. Bronchoscopy is done if indicated. Latelywe have used EUS in case of diagnostic dilemmas. Since ourpolicy is of offering surgery as the primary modality of treat-ment and attempting resection in all reasonably fit patientswith localized tumor; EUS, PET and invasive staging do notoffer any significant advantage in clinical decision making.


SURGERY 17

a feeding jejunostomy under local or generalanesthesia. Pulmonary preparation includes steaminhalation, incentive spirometry, bronchodilatorsand antibiotics, and pulmonary function tests asrequired. An FEV-1 (forced expiratory minute vol-ume at one second) under 65% indicates highsurgical risk.[102] The hemoglobin should exceed9 gm%. Transfusion may be required. Hydration,serum electrolytes, and urine output should beoptimal before surgery. Orodental hygiene shouldbe carefully assessed as these patients are oftenchronic tobacco chewers. The obstructed esopha-gus is often infected with fungi, especially Can-dida.[68] We routinely use antifungal lozenges insuch patients to decrease the incidence of fungalinfections postoperatively.

1.8.2 Aims of Treatment

The ideal objective is the total eradication ofthe disease with full functional restoration. Thisis not possible in most patients, therefore treat-ment is focused on relief of dysphagia, relief fromsialorrhea, and prevention of recurrent aspiration.However, for the last two decades some sur-

geons have been attempting curative surgery foresophageal carcinoma and have reported goodresults.

1.9 SURGERY

Czerny[103] is credited with the first esophagealresection in humans. Torek[104] performed the firsttransthoracic esophagectomy.Surgery is still the gold standard of treatment

for esophageal carcinoma. The basic surgical pro-cedure consists of removal of a part or whole ofthe esophagus and its replacement with a con-duit. There are several controversies in the surgicaltreatment of esophageal carcinoma. Of these theimportant areas are addressed below.

1.9.1 Surgery – Treatment of Choice

Curative treatment of esophageal carcinoma maybe attempted by surgery or radiotherapy.Surgery best resolves dysphagia, sialorrhea, and

recurrent aspiration. However, surgery is associ-ated with mortality up to 10%–20%, althoughthis drops to less than 5% in specialized units.In comparison, more than 50% of patients receiv-ing only radiotherapy develop strictures, and abouthalf of these are due to local recurrence oftumor.[105] Complications of high dose radiother-apy can be as devastating as the morbidity fol-lowing surgery. There are two randomized studieswhich compare surgery with radiotherapy. Bothconclude that surgery is superior to radical radio-therapy.[106,107]

1.9.2 Perioperative Management

Several procedural protocols are devised by teamsthat routinely carry out esophageal surgery. Theseare designed to minimize operative complications,improve the chances of successful surgery, as wellas to speed recovery (Table 1.10).[108,109]

fyTABLE 1.10 Perioperative measures for bestresults[108,109]

• Optimization of the preoperative comorbid illnesses• Colon preparation in lower third carcinoma or previous

gastrectomy (in case the stomach cannot be used as aconduit). Assess the mesenteric circulation with angiog-raphy in those susceptible to atherosclerosis. In Westernpopulations exclude diverticular disease

• Careful intraoperative monitoring and fluid manage-ment

• Use of double lumen endotracheal tube; this facilitatesexposure during thoracotomy

• Deep vein thrombosis prophylaxis• Feeding jejunostomy during surgery, to start early post-

operative enteral feeding

Part I / Esophagus


1.9.3 Operability and Resectability

Operability is the feasibility of surgery accordingto both tumor factors and patient factors. Between50% and 80% of patients are operable, that is, theyare explored surgically.[110]

Resectability is the feasibility of tumor resec-tion in operable patients. Seventy percent toninety percent of operable patients have resectabletumor.[107] If the surgeon believes in undertak-ing palliative resection, the resectability rate ishigher.[111]

1.9.4 Subtotal versus PartialEsophagectomy

Submucosal lymphatic flow in the esophagusforms an important route of malignant spread.Submucosal deposits are often found far from themain tumor, especially in squamous cell carcino-mas, and form one cause of multicentric tumors.Deposits may occur as far away as 15 cm from themain tumor, and are often not obvious on nakedeye examination.[112,113] This makes a strong casefor total esophagectomy (in fact, a near-totalesophagectomy, because a small part of the cervi-cal esophagus is left behind for anastomosis anda good functional result). While some workersfavor esophageal resection 5–10 cm proximal tothe main tumor, the incidence of local recurrenceis unacceptably high.[114]

A total esophagectomy also gives the opportu-nity to perform the anastomosis in the neck withits advantages.

1.9.5 Transhiatal versus TransthoracicEsophagectomy

Esophagectomy is ordinarily performed throughincisions in the abdomen and chest. The chest inci-sion allows for dissection under vision. In addition,

there is always the potential for a radical surgeryand cure. The gastroesophageal anastomosis maybe carried out in the chest (infrequently), or in theneck (most cases), in which case a neck incision isadded.A transhiatal esophagectomy is carried out

through abdominal and neck incisions. The sur-geon removes the entire esophagus by manipulat-ing the esophagus through the esophageal hiatusat the diaphragm, and through the neck behind themanubrium sterni. This surgery is always palliative(recurrence is locoregional in 25%, systemic in15%, and both in 15%).[115] The gastro-esophagealanastomosis is always made in the neck. Sincethere is no thoracic incision, transhiatal esophagec-tomy theoretically has lower morbidity.Most studies comparing the two approaches

are retrospective and fail to show significant dif-ference in terms of blood loss, mortality, andpulmonary or other morbidity (Table 1.11).[116–119]

In literature, there is always a bias due tothe poor pulmonary risk patients being favoredto undergo transhiatal rather than transthoracicesophagectomy.

fyTABLE 1.11 Retrospective comparison oftranshiatal and Ivor Lewistransthoracic esophagectomy from areview of 33 series[119]

2675 patients undergoing transhiatal esophagectomy,2808 patients undergoing Ivor Lewis transthoracicesophagectomy

• Respiratory complications (24% vs. 25%)• Cardiovascular complications (12.4% vs. 10.5%)• Wound infection (8.8% vs. 6.2%)• Chylothorax (2.1% vs. 10%)• Anastomotic strictures (28% vs. 16%)• Recurrent laryngeal nerve injury (11.2% vs. 4.8%)

The 30-day mortality was lower for transhiatal group(6.3% vs. 9.5%) mainly due to the high mortality ofthe anastomotic leaks in the transthoracic group. Theoperating time was longer for the Ivor Lewis group.


SURGERY 19

FIGURE 1.4Esophagectomy specimen showing the entire esophagus and the tumor at the lower end.

Patients at high risk for pulmonary morbid-ity should be selected for transhiatal esophagec-tomy. Those with bulky tumors, or suspicionof involvement of the tracheobronchial tree oraorta should undergo transthoracic esophagec-tomy.

1.9.6 Radical versus StandardEsophagectomy

Radical esophagectomy consists of en bloctransthoracic esophagectomy with lymph nodedissection. The objective is to remove the tho-racic duct, azygos vein, posterior pericardium,

bilateral adjacent parietal pleurae, and theright intercostal vessels adjacent to the tumor(Fig. 1.4).[120,121]

Akiyama et al. and others reported that 12.2%of the upper esophageal cancer involved abdomi-nal nodes and 27.2% of lower esophageal cancersinvolved cervical nodes.[50, 122, 123] There are threelymphatic fields (upper abdominal, mediastinal,and cervical) in relation to the esophagus. Lym-phadenectomy may be two field, removing theupper abdominal and mediastinal nodes, or threefield. Patients with no nodes involved do not ben-efit from lymphadenectomy, nor do patients withextensive lymphatic dissemination.[62–64,124–128]

Part I / Esophagus


The morbidity of radical lymphadenectomyis predominantly pulmonary (about 20%–30%).[122,129] Recurrent laryngeal nerve injuryoccurs in 40%–70% of cases, particularly inthree-field lymphadenectomy.[126,129] The resultis hoarseness, recurrent aspiration, and a highincidence of permanent tracheostomy.[130] Thepulmonary morbidity also occurs due to bronchor-rhea following damage to the tracheobronchialvagal fibers, and ischemic ulcers occur inthe tracheobronchial tree. Phrenic nerve palsycontributes to the pulmonary infections andatelectasis. Anastomotic leak is common (about20%). The long-term sequelae are permanenttracheostomy, hoarseness, recurrent aspirations,and functional dysphagia. Studies on the qual-ity of life after radical surgery have shown thatthese problems lead to a poor quality of life, lackof weight gain, and malnutrition on long-termfollow-up.[124,131]

There is little literature on direct compar-ison between radical and standard esophagec-tomy. The morbidity of radical esophagectomyis high, and the benefits doubtful.[132,133] Eventranshiatal esophagectomy may show a 5-yearsurvival over 20%.[134,135] A radical lymphadenec-tomy is therefore best reserved for clinicalstudies.

1.9.7 Selection of Approach

For a lower third esophageal squamous cellcarcinoma, the options are a partial esophago-gastrectomy with an esophagogastric anastomosisin the chest (through a left or right thoracotomy), ora subtotal esophagectomy (transhiatal or transtho-racic) with an esophagogastric anastomosis in theneck.Where the stomach cannot be used, the colonmay be used to replace the esophagus.For adenocarcinoma of the lower esopha-

gus (Siewert’s type-I), a partial esophagectomy

may be suitable for small lesions at the car-dia provided a proximal clear margin of at least5 cm is obtained.[136] These tumors require resec-tion of the proximal stomach with about halfof the lesser curvature to obtain this tumor-freemargin. An esophagogastric anastomosis may bedone through the hiatus via a thoracotomy. Forthe Siewert’s type-II and type-III adenocarcino-mas (cardia and subcardia carcinoma) the rec-ommended surgery is total gastrectomy with D2type lymphadenectomy and partial esophagec-tomy.[59]

For middle and upper third carcinoma of thethoracic esophagus, the procedure is a subtotalesophagectomy with an esophagogastric anasto-mosis in the neck. A thoracotomy is usuallyrequired. Transhiatal esophagectomy may be donefor palliation in small lesions.Carcinoma of the cervical esophagus can be

dealt with by a combined pharyngo-laryngo-esophagectomy with neck dissection of nodes anda permanent tracheostomy.[137,138] The thoracicesophagus is removed by a transhiatal dissec-tion. The conduit of choice is stomach. Colonmay be used if stomach is not suitable. For smalltumors, a local excision of the cervical esophagusand replacement with a jejunal free graft can bedone by surgeonswith experience inmicrovascularsurgery.

1.9.8 Minimal Access Esophagectomy

Minimal access esophagectomy is feasible,[139] butdoes not as yet have demonstrable advantage overopen surgery. The benefit of small incisions isoffset by the increased time of single lung anes-thesia. Further, the extent of mediastinal dissectionremains the same, therefore the morbidity is sim-ilar. Port site recurrence is another concern. Thefollowing are the main steps of minimal accessesophagectomy:


SURGERY 21

• Thoracoscopic esophageal mobilization.• Video assisted transhiatal mediastinal esopha-

geal mobilization using a laparoscope insertedthrough the diaphragmatic hiatus.

• Laparoscopic gastric mobilization.• Laparoscopic and thoracoscopic gastric and

esophageal mobilization.• Mediastinoscopic dissection.

1.9.9 Choice of Conduit and Route

Several organs have been used as conduitsto replace the esophagus after esophagectomy(Table 1.12).The stomach is the overwhelming favorite

(Table 1.13). The gastroepiploic arcade providesa good collateral blood supply, and the robust

fyTABLE 1.12 Structures used as esophagealreplacements

• Stomach• Greater curvature gastric tube• Reversed gastric tube• Nonreversed gastric tube• Right colon• Left colon• Jejunum (Roux loop)• Jejunal (free graft)• Myocutaneous free or pedicled grafts

fyTABLE 1.13 Comparison of conduits after esophagectomy

Stomach Colon (left) Jejunum

Vascularity Very good Good UncertainLength Adequate Adequate ShortEase Easy Tedious CumbersomeReflux ++ – +Nutritional problems + – –Respiratory problems + – –Preoperative preparation – + –Anastomotic complications + ++ ++

submucosal plexus takes care of the blood supplyat the fundus.The neoesophagus can be taken up through

several routes (Table 1.14). It may be made totraverse the posterior mediastinum (usual) in placeof the resected esophagus, or the presternal route,anterior to the heart. The conduit may even betaken up presternally, directly under the skin!This path requires the longest length of con-duit (4 cm more than the posterior mediastinalroute).

1.9.10 Esophageal versus NeckAnastomosis

In patients who have distal third tumors, thesurgeon has a choice: subtotal esophagectomywith esophagoconduit anastomosis in the neck,or partial esophagectomy with the anastomosisin the chest. The chest anastomosis infrequentlyleaks, but when it does the mortality is closeto 50%.[140] The rate of leak for the anastomo-sis in the neck is higher, but it usually heals,and rarely if ever leads to sepsis and mortality,since the pleural cavity and mediastinum are notcontaminated.[141]

Gastroesophageal reflux is also commoner inchest anastomoses. Recurrent Barrett’s metaplasiahas been reported due to such reflux.

Part I / Esophagus


fyTABLE 1.14 Routes of pull-up of conduit after esophagectomy

Route Advantages Disadvantages

Posterior mediastinal • Shortest • May be affected by residual tumor,• Best function recurrence, scarring, and• Least complications adjuvant radiotherapy

Substernal (retrosternal) • Always available • Longer route• Compression at thoracic inlet• Graft angulation• Cardiac access restricted

Subcutaneous (presternal) • Easiest to construct • Longest route• Avoids mediastinum altogether • Cosmetically unacceptable

• Poor function and emptying problems

Transpleural • Useful for left thoracic approach • Displaces lung

Endoesophageal • Short and direct • Not usually feasible• Straight lie of conduit • Constriction of conduit

1.9.11 Need for a Pyloroplasty orPyloromyotomy

The stomach is denervated after esophagectomy.It was thought that the pylorus would forma barrier to the normal emptying of the den-ervated stomach after pull-up. Some surgeonstherefore carry out a pyloroplasty or pyloromy-otomy. However, the pulled-up stomach drainswell enough, and the benefits of pyloroplasty areunproved.[142–145] We favor a selective approach inwhich the pylorus is manually dilated at surgery,and pyloromyotomy/pyloroplasty is reserved for avery muscular and narrow pylorus.

1.9.12 Complications of Esophagectomy

The accepted in-hospital mortality of esophagec-tomy reported from experienced units world overis about 5% or less (Table 1.15). Large tumors(locally advanced) would require difficult surgeryand hence are at higher risk of both morbid-ity and mortality. Patients facing major post-operative complications such as an intrathoracic

anastomotic leak or severe pulmonary infection areat a higher risk of death.[146]

1.9.13 Intraoperative Complications

Injury to various organs in the abdomen, chestor the neck, and hemorrhage are the major intra-operative complications (Table 1.16). Mediastinalbleeding may occur from the esophageal arteries,aorta, pulmonary vessels, or from cardiac injury.Transhiatal esophagectomy is based on the fact thatperiesophageal arteries break up into a network offine vessels 1 cm before entering the esophagus. Ifthe dissection plane is kept close to the esophagusthe chances of major hemorrhage are slim.Tracheobronchial injury occurs in about 1% of

the cases and may be recognized during opera-tion or after the endotracheal tube is removed. Theonly remedy is direct repair. Pneumothorax is socommon (25%–75%) after transhiatal dissectionthat it should be considered a sequel rather thana complication. Recurrent laryngeal nerve injurycan occur in the neck or the chest and leads topostoperative hoarseness and recurrent pulmonary


SURGERY 23

fyTABLE 1.15 Results of selected series of esophagectomy for carcinoma(transhiatal and radical)

Study No. Mortality Five-year survival

Transhiatal

• Orringer MB (2001) 800 4% 23%• Gupta NM (1996) 250 6% 5%• Authors’ series (1999)∗ 78 6.4% 21.3%• Authors’ series (2002)∗∗ 367 11% 38%• van Sandick JW (2002) 115 3% 45% (3-year survival)• Dudhat SB (1998) 80 7.5% 37%

Radical

• Stilidi I (2003) 147 6.1% 28%• Akiyama H (1994) 913 5.2% 42%• Altorki N (2002) 80 5% 51%• Swanson SJ (2001) 250 3.6% 48% (3-year survival)• Collard JM (2001) 235 5% 49%• Nishimaki T (1998) 190 4.7% 41%

∗Prashad et al. 1999; ∗∗Rao et al. 2002

aspiration. The incidence varies from 1% to 20%.It may recover if it is due to neuropraxia, but com-plete injury may require medialization of the cordlater if adequate compensationby the opposite corddoes not occur.

1.9.14 Early Postoperative Complications

Pulmonary complications are the most com-mon cause of morbidity after esophagectomy(Table 1.7). Atelectasis, pneumonitis, and pleu-ral effusion predominate. Intensive physiotherapyand pulmonary toileting is extremely importantin improving results. Cardiac complications aremost commonly supraventricular arrhythmias, andthe incidence is up to 30%.[147] The most com-mon of these is atrial fibrillation and may occurduring or after surgery. Studies of digoxin or beta-blockers have proved unsuccessful in preventingthese.An anastomotic leak is the most dramatic com-

plication of this surgery.[148] The incidence varies

widely in various studies (2%–41%).[149] The fac-tors that increase risks of leak are poor vascularityof the conduit (less often esophageal blood sup-ply), neck anastomoses (which leaks more oftenthan intrathoracic), and poor nutritional conditionof the patients. Some leaks in the cervical anasto-mosis can bemanaged by continued oral intake in alocalized salivary fistula, using digital occlusion ofthe fistula during swallowing. The tract is cleanedlater with a swallow of water. The intrathoracicleak that causes sepsismay require reoperation anddismantling of the anastomosis.Chylothorax should be suspected in case of

excessive drainage from the intercostal drains. Itoccurs due to thoracic duct injury in the chestbehind the esophagus. The incidence is usu-ally about 1%. The classical milky discharge isseen only if the patient is on an enteral diet.Confirmation is obtained when the patient is given100 gm of cream or butter via the feeding jejunos-tomy. The discharge turns milky, and on standinghas an upper milky and a lower clear layer. The

Part I / Esophagus


fyTABLE 1.16 Complications of esophagectomy

Intraoperative complications

• Injury to tracheobronchial tree, lungs, pleura, heart,major vessels, etc.

• Hemorrhage (aorta, pulmonary vessels, esophagealvessels, etc.)

• Pneumothorax• Recurrent laryngeal nerve injury• Hypotension and arrhythmias

Early postoperative complications

• Pulmonary complications (atelectasis, collapse, con-solidation, pleural effusion, etc.)

• Cardiac complications (arrhythmias, hypotension,myocardial infarction)

• Leak (anastomotic leak, gastric suture line leak, etc.)• Conduit necrosis• Mediastinitis, wound infection• Intestinal obstruction• Chylothorax

Late postoperative complications

• Anastomotic stricture• Dumping syndrome• Diarrhea• Nutritional deficiencies (vitamin deficiencies, weight

loss, osteomalacia)• Gastric outlet obstruction• Reflux and aspiration

milky layer dissolves and clears up on addingan organic solvent like ether or acetone. Thedrain fluid can be analyzed for chylomicrons andtriglycerides for further evidence. Lymphangiog-raphy and lymphoscintigraphy are for themost partunnecessary in clinical practice. The managementis initially conservative, and consists of a mediumchain triglyceride diet orally supplemented byparenteral nutrition. Indications for surgery arehigh discharge despite conservative management(> 1 liter/d after 5 days), nutritional depletion orwater, and electrolyte imbalance. Surgery consists

of suture ligation of the thoracic duct above andbelow the site of leak.Other early postoperative complications are

conduit necrosis (especially in case of colon),intestinal obstruction, and hiatal herniation.

1.9.15 Late Postoperative Complications

Anastomotic stricture is usually a sequel of amajorleak (Table 1.7). The incidence is between 5% and30%. Other factors which increase the chancesof a stricture are a stapled anastomosis and asmall esophagus.[150] We have introduced a sim-ple method of managing the cervical strictures byteaching the patient self-dilatation using a Foley’scatheter.[151] The low cost and ease of the pro-cedure increase the patient compliance and givegood results. Intrathoracic anastomotic stricturesrequire dilatation in hospital with various dila-tor systems, e.g., Savary-Gilliard dilators. Otherimportant late complications are gastric outletobstruction, dumping syndrome, nutritional prob-lems due to vagotomy, and loss of gastric reservoircapacity.

1.10 RADIOTHERAPY

Multimodal therapy for esophageal carcinoma isthe current field of interest. Lot of hope has beenraised by the results of various combinations ofradiotherapy and chemotherapy, but lot of workneed to be done before these can be universallyrecommended.

1.10.1 Primary Radiotherapy

Squamous cell carcinoma of the esophagus is aradiosensitive tumor. Radical radiotherapy has tra-ditionally been the choice of treatment in patientswho were considered too weak to withstandsurgery. Conventional external beam radiotherapy


RADIOTHERAPY 25

(EBRT) is administered by high energy photonbeams. Lower energy radiation is frequently usedin brachytherapy. When radiotherapy is used asa single modality in definitive treatment, a doseof 60–64Gy in conventional fractionation of 180–200 cGy/day is used. Primary radiotherapy resultsin 5 year survival of 2%–20%[152] and the resultsare best with early lesions less than 5 cm in length,noncircumferential and nonobstructing. Radiationfields extend 5 cm above and below the tumor and2.5–3 cm radially around the tumor.Patients should be in good general health for

tolerating high dose radiotherapy.The early toxicity of radiotherapy includes a

marked esophagitis, redness and irritation of skin,decreased blood counts, and hair loss in treatedarea. Other toxicity includes nausea, vomiting,ulceration, hemorrhage, radiation injury to spinalcord and lungs. It was initially thought that radio-therapy caused increased incidence of tracheo-esophageal fistulae and hence this complicationwas thought to be a contraindication to radiother-apy. Recent results have shown that this is not thecase, and radiotherapymay in fact facilitate closureof some tracheoesophageal fistulae.[153,154]

Late complications of radiotherapy includeesophageal stricture, esophageal motility disor-ders, and pulmonary fibrosis. A late esophagealstricture is the most important complication ofradiotherapy from the functional standpoint. Theincidence is 12%–50%, and the median time todevelop stricture is 6 months. About half of theseare malignant due to tumor recurrence.Two randomized trials directly comparing

surgery versus radiotherapy have shown thatresults are better with surgery.[106,107]

1.10.2 Brachytherapy

Iridium-192 is the isotopewhichhas renewed inter-est in brachytherapy. First a catheter is inserted into

the esophagus after identifying the region of inter-estwith bariumswallowor endoscopy.Radioactivesource is inserted into this catheter. Two techniquesare used — high dose rate (HDR) and low doserate (LDR) brachytherapy. High dose rate (HDR)brachytherapy uses short intense applications ofseveral minutes and requires advanced automatedtechnology. With low dose rate brachytherapythe treatment is administered over a total treat-ment time of 24–48 hours, and is less technol-ogy intensive but requires prolonged esophagealintubation. The low availability of brachyther-apy and paucity of data showing its superi-ority over EBRT has resulted in low clinicalusage.

1.10.3 Preoperative Radiotherapy

Enthusiasm for preoperative radiotherapy dwin-dled after several randomized trials reported noclear benefit.Recently,wehave showna resectabil-ity rate of 81% using a novel regime of 25Gypreoperative radiotherapy over 5 days.[155] Therewere no side effects, and in the unselected patientpopulation the actuarial 5-year survival was 32%.The proposed advantages were down-staging ofthe tumor, sterilization of the margins reducingspill of cancer cells during surgery, and radio-therapy induced edema which makes resectioneasier.[156]

A meta-analysis of all randomized trials on therole of preoperative radiotherapy came out with asmall but statistically insignificant survival advan-tage of about 3%–4% in favor of preoperativeradiotherapy.[157] To demonstrate that the effect isconsistent, a much larger trial is necessary. In viewof the high toxicity of the preoperative chemo-radiotherapy schedules tested in literature, thisrelatively nontoxic regime makes sense till clearanswers are available.

Part I / Esophagus


1.10.4 Postoperative Radiotherapy

Postoperative radiotherapy has traditionally beenout of favor after esophagectomy because thepatients are unable to tolerate adjuvant therapyafter such major surgery. In addition the radiother-apy would damage the neoesophagus. Most evi-dence indicates no survival benefit and increasedproblems due to the stomach being affected. Post-operative radiotherapy has thus been reserved forgross residual disease or positive resection mar-gins though the evidence for this is weak. How-ever a recently published large Chinese series hasshown good results with postoperative radiother-apy.[158] More work is needed to validate thesefindings.

1.11 CHEMOTHERAPY

Single agent chemotherapy using drugs such as 5-fluorouracil (5-FU), mitomycin-C, cisplatin, vin-desine, methotrexate, bleomycin, and etoposideyields complete tumor response of 5% to 15%and partial response in an addition 10% to 25%.Thus the overall response rate is about 40%. Com-bination chemotherapy results in complete tumorresponse of about 5% to 15% and partial tumorresponse of about 40% to 50%.

1.11.1 Preoperative Chemotherapy

Most small trials have been unable to show asurvival advantage with preoperative chemother-apy. The American Intergroup-0113 trial[159]

and the recent British Medical Research Counciltrial[160] are the two largest trials of preopera-tive chemotherapy. The former showed no benefit,while the latter showed survival benefit of preop-erative chemotherapy. Thus the data is conflicting,but it is clear that patients who respond to pre-operative therapy are a good prognosis group and

in general do well especially in case of completepathological response.

1.11.2 Postoperative Chemotherapy

Little data exists on the adjuvant use of chemother-apy. Postoperative adjuvant chemotherapy doesnot appear to improve survival in these patients.

1.11.3 Chemoradiotherapy

1.11.3.1 Neoadjuvant chemoradiotherapy

A combination of preoperative chemotherapy andradiotherapy has resulted in complete pathologicalresponse rates of 25%–40%.[161–163] The avail-able studies of neoadjuvant chemoradiotherapyare small, often flawed, and show no consistentimprovement in survival. Locoregional control isimproved. Patients with complete response (25%–40%) have a survival advantage. Adenocarcinomaand squamous cell carcinoma respond equallywellto the regimes tested.What often remains unsaid in the critical analy-

sis of neoadjuvant therapy is the toxicity profile.These patients are often nutritionally depletedand in poor health. The side effects of therapyare pronounced and lead to a high dropout rate.Although data is conflicting, we believe that theregimes tested so far are too toxic, even thoughthey do work, and add to the mortality and mor-bidity of surgery. We have used a low dose 5-FUand cisplatin based chemotherapywith 25Gy shortcourse radiotherapy and have got good results in apilot study. This is an active area of research inesophageal carcinoma and may provide answersin the near future.[164]

Selective surgery after chemoradiotherapy hasbeen studied in a few studies. The results in thesestudies have been encouraging but much more


PALLIATION 27

work needs to be done to establish clear andvalidated criteria for avoiding surgery.[165]

1.11.3.2 Adjuvant chemoradiotherapy

Insufficient controlled literature is available on thisaspect to be able to recommend it after curativeresection.

1.11.3.3 Primary chemoradiotherapy

The rationale of adding chemotherapy toradiotherapy was to take care of systemicmicrometastasis and have a local synergistic effectwith radiotherapy. There are six randomized tri-als of primary chemoradiotherapy published sofar. Most studies have used suboptimal dosagesof chemotherapy or radiotherapy. The landmarkRTOG (Radiation Therapy Oncology Group)study[166] and the ECOG (Eastern CooperativeOncology Group) study[167] showed a 5-yearsurvival of 9% to 26% with chemoradiotherapycompared to the radiotherapy. However, the localfailure (local persistence or recurrence) rates withprimary chemoradiotherapy were high, and therewas no direct comparison to surgery exist in liter-ature. Combined chemoradiotherapy gives betterresults than only radiotherapy but is also associ-ated with a definitely higher incidence of acutetoxicity.[168] Thus, so far primary chemoradio-therapy is reserved for reasonably well pre-served patients who have unresectable tumoror in whom the operative risk is prohibitivelyhigh.

1.12 PALLIATION

Two important clinical features that need pallia-tion in these patients are dysphagia and tracheo-esophageal fistula. There are several methods andtechniques of palliation of dysphagia.

1.12.1 Dilatation

Tumor dilatation using bougies or balloon dila-tors are the oldest method of palliation. Used inisolation the relief is short lived, therefore it isused in combination with other procedures suchas placement of a stent. The dilatation requiredfor placing a plastic stent is about 15mm,while the applicator for a self-expanding metallicstent requires only about 10mm lumen. With-out stenting, dilatation large enough to palliatedysphagia is fraught with complications such astumor rupture and fistulization. Recently balloondilatation has been combined with chemoradio-therapy.[169]

1.12.2 Surgical Palliation

Esophagectomy provides excellent and long last-ing relief from dysphagia. As discussed earlier, thephilosophy of surgical treatment in some centers,including ours, is to provide relief from symptoms.We would offer esophagectomy in all reasonablyfit patients. For this reason extensive staging usingendoscopic ultrasound, PET, and invasivemethodsis not done. Comparison of surgery with nonsur-gical methods of palliation revealed that surgeryprovided a much better palliation and quality oflife after 3 months.[170] Hence features which sug-gest a short (< 3 months) survival, such as poorperformance status, obvious local invasion, non-regional nodal metastasis, and distant metastasis,should discourage the use of palliative resection.Surgical bypass using the stomach, colon,

or jejunum was used extensively earlier. TheKirschner operation using the retrosternal stomachpull-up to anastomose to the cervical esophaguswas the most popular approach. There is no doubtthat surgical bypass provides the best relief fromdysphagia. However, it remains a formidable oper-ation in patients with advanced disease who are

Part I / Esophagus


at poor surgical risks and the mortality and mor-bidity are high. Recently the Hong Kong grouppublished their experience with the Kirschneroperation.[171] The high mortality and morbiditylead them to conclude that it should be reservedfor patients with unresectable disease encounteredintraoperatively.

1.12.3 Endoprosthesis

1.12.3.1 Plastic tubes

These have historical importance and infrequentlyused after the advent of self-expanding metallicstents. They are of two types: the ‘pull’ type andthe ‘push’ type.Recently a series from India demonstrated

good results with a modified tube design andgradual tumor dilatation.[172] The overall mor-bidity was 16% and the mortality was 3.9%.The estimated treatment cost was very low. Self-expanding plastic stents (SEPS) are now beingdeveloped, and feasibility studies have showngoodresults.[173]

1.12.3.2 Self-expanding metallic stents

The most commonly used stents are: (a) GianturcoZ-stent, (b) wall stent, (c) ultraflex stent, and(d) esophacoil stent. These can be uncoveredor covered. The covered stents are coated withpolyurethane and are specifically useful in pre-venting tumor in-growth and in tracheoesophagealfistulae. The advantage of self-expanding metallicstents (SEMS) is the small delivery system. SEMSneed minimal lumen (up to 10mm) for placementof the applicator. While choosing the length of thestent, 5 cm should be added to the estimated tumorlength to account for shortening of the SEMS.Before deployment the proximal and distal ends ofthe tumor can bemarked bymucosal contrast injec-

tion, by endoclipping, or by external radio-opaquemarkers. The stent is placed under endoscopic, flu-oroscopic, or combined control. Both proximal anddistal release systems are available. Only the ultra-flex stent, which hasweak radial force,may requiredilatationwith a balloon for full expansion. Each ofthese SEMShas specific propertieswhich continueto evolve over time. One innovation has been adistal valve to prevent reflux in stents deployedacross the gastroesophageal junction.The initial technical success rates are high

(90%–95%). Early complications are mild chestpain and incomplete expansion. Late complica-tions include tumor ingrowths, stent migration,food impaction, hemorrhage, and fistulization. Ina review the incidence of late complications was36%.[174] There have been concerns about theincreased incidence of fistulae in SEMS placementafter chemotherapy or radiotherapy. It has thusbeen recommended that 4 weeks should elapsebetween any such treatment and placement ofSEMS.

1.12.4 Photodynamic Therapy

This unique form of treatment uses the photosen-sitizing drugs such as the FDA approved Photofrinand 5-aminolevulinic acid. Photosensitizers aredrugs which emit singlet oxygen on exposure tolight of a particular wavelength. This singlet oxy-gen is cytotoxic to the tumor cells. The usual doseofPhotofrin is 2mg/kg and the patient is exposed tolaser at 690 nmwavelength after 48–72 hours. Theadvantage of photodynamic therapy is that it can beused in long, obstructing, tortuous, angulated, andcervical lesions as well. The disadvantage is theskin photosensitivity for 4 weeks. 5-ALA has beenreported to have fewer side effects as compared toPhotofrin. Complications reported are perforation,fistulae, and strictures in 10%–20%.[175]


CONCLUSIONS 29

1.12.5 Laser Therapy

The Nd:YAG (neodymium: yttrium aluminumgarnet) laser has been the workhorse of laser ther-apy. Recently KTP:YAG (potassium titanyl phos-phate:YAG) laser has been used for this indication.Laser can be used in a high power noncontactmodeor low power contact mode. The tumor can betreated in an antegrade or prograde fashion. Tumordilatation and retrograde technique is preferred. Ina totally obstructing tumor antegrade technique isused, and charred debris needs to be removed toproceed further. In addition the chances of per-foration are higher with the antegrade technique.The overall functional success is about 75%–80%.Major complications are infrequent and consist ofperforation (3%), fistula (2.3%), and hemorrhage(1.4%).[176] The disadvantage of laser therapy isthe recurrent dysphagia (in about 33% to 50%) andthe need for repeated treatment every 4 to 6 weeks.To obviate this disadvantage laser therapy has beencombined with brachytherapy and EBRT, and hasshown good results.

1.12.6 Palliative Radiotherapy andChemoradiotherapy

Radiotherapy palliates dysphagia in about three-fourths of patients. We have used a short courseintensive regime of radiotherapy of 25Gy overfive fractions of 500 cGy each in 5 days, and havegot good results in the palliation of dysphagia.The problems are that the relief is not immediate,and the radiotherapy side effects may reduce thequality of life. The improvement starts in 2 weeksand the median time to maximal improvement is4 weeks (range 2 to 21 weeks). Late esophagealstrictures are common and reduce the quality ofpalliation.Combined modality chemoradiotherapy

improves dysphagia in 59%–88% of the patients.

Keeping in mind the toxicity of high dose regimesthese are best applied if the performance status isat least fair, and the life expectancy is more than3 months. For patients with poor life expectancylower dose regimes are better applied. Chemo-radiotherapy suffers the same disadvantages forpalliation as with radiotherapy alone.

1.12.7 Injection Therapy for Palliation

Various chemicals have been injected in thetumor in an attempt to induce necrosis andrelieve dysphagia. These include alcohol, poli-docanol, chemotherapeutic agents, and others.The response is variable. However this formsrelatively cheap method of temporarily reliev-ing dysphagia when compared to the expensiveSEMS.

1.12.8 Palliation of EsophagorespiratoryFistula

The presence of esophagorespiratory fistula in apatient of esophageal carcinoma indicates a shortsurvival. The presence of constant contaminationof the airway from esophageal contents results ina poor quality of life. The options of treatmentinclude covered stents (SEMS) and surgical bypass(Kirschner operation). Lately, chemoradiotherapyhas shown to result in closure of fistulae in somepatients.[153,154]

1.13 CONCLUSIONS

The poor prognosis of esophageal carcinomaas concluded by Earlam two decades ago hasshown a change for the better in the last twodecades. The large experience (1970–2001) fromthe MD Anderson Cancer Center[177] exempli-fies the improvement in resectability and (78% to94%) mortality (12% to 6%). The current focus

Part I / Esophagus


is on the results of radical surgery and the advan-tage gained from neoadjuvant therapy. In the near

future, molecular biology may throw up answerswhere conventional surgery has failed.

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