CHAPTER 6 MALIGNANT CONDITIONS INVOLVING THE OESOPHAGUS, STOMACH, SMALL INTESTINE, GALL BLADDER AND BILE DUCT

KEYPOINTS

• In upper gastrointestinal tumours, accurate preoperative staging is important in determining appropriate management.

• Accurate staging includes clinical assessment and investigation of tumour and patient factors.

• Stage of disease directly correlates with outcome.

• Newer modalities of investigation include capsule endoscopy, endoscopic and laparoscopic ultrasound.

• Multidisciplinary care is now standard.

• Multimodality therapies are now common.

OESOPHAGOGASTRIC CANCERS

Gastric cancer incidence and mortality has fallen dramatically over the last 50 years in many regions, but probably remains the second most common cancer worldwide. The likely cause for this reduction is the disappearance of Helicobacter pylori and possibly greater consumption of fruit and vegetables, the reduced intake of salted, pickled and preserved foods, and improvements in refrigeration.

The incidence of gastric cancer varies worldwide, with the highest incidence being in Japan. Low rates can be expected in North America, India, Australia and New Zealand and northern Europe. The rates are also higher generally in lower socioeconomic groups and in males (male to female ratio 2:1). Gastric cancer is largely a disease of older age groups in most countries.

Despite a marked decline in fundal and distal tumours, there is a rising incidence of adenocarcinomas of the gastro-oesophageal junction and gastric cardia, particularly in Western nations, and predominantly in males. Comparatively high rates of this tumour are evident for the United Kingdom/Ireland, northern Europe, Australia and New Zealand, China and North America. The increase in incidence of cardia lesions has been associated with parallel increases for adenocarcinomas of the lower oesophagus, where hyperacidity, reflux oesophagitis, Barrett’s oesophagus and obesity have been proposed as likely risk factors. This may imply that there are, in fact, two diseases differing from each other in epidemiology, aetiology, pathology and clinical expression. It is important to distinguish cardia and lower-third oesophageal adenocarcinoma from gastric cancer invading the lower third of the oesophagus, as treatment options may vary.

Clinical

Common presenting symptoms include weight loss, abdominal pain, nausea, anorexia and dysphagia. Easy satiety, reflux symptoms and symptoms of anaemia may be present. Background history may include previous peptic ulcer, previous history of polyps (gastric or colonic) and should include assessment of risk factors. A careful history of factors that may increase operative morbidity and mortality should also be sought (cardiac, respiratory, other systemic illness, anticoagulants, etc).

Risk factors

Oesophageal

There is a strong association between smoking and alcohol consumption and oesophageal squamous cell cancer. Human papilloma virus may be an important causative agent for oesophageal (squamous cell) cancer. Other risk factors include achalasia, chemical strictures, diverticula, previous radiation therapy and post-cricoid webs. Barrett’s mucosa predisposes to oesophageal adenocarcinoma, as does smoking and obesity, while aspirin use may be protective.

Gastric

Precursors of gastric cancer include chronic gastritis (autoimmune and acquired), intestinal metaplasia/dysplasia, gastric polyps (adenomatous polyps, rare in hyperplastic polyps) previous gastrectomy (>15 y post resection), pernicious anaemia and, most importantly, Helicobacter pylori infection. Infection with H. pylori induces chronic gastritis. Whether treatment of H. pylori infection will diminish the risk of gastric cancer is currently under investigation.

Dietary factors are important. A high consumption of fruit and vegetables is negatively correlated with risk of gastric cancer. These food items are thought to have a protective antioxidant effect. A high intake of salted foods, and potentially of smoked, cured and pickled foods, is thought to be a risk factor. These foods may include elevated levels of N-nitroso compounds, which have been shown to be potent carcinogens in animal experiments. There is also additional preliminary evidence that high-nitrate and high-starch diets may be risk factors, whereas garlic, onions and green tea may have protective effects. Ionising radiation is an established cause, based on exposure to radiation from atomic bombs and radiation therapy in certain patient groups (ankylosing spondylitis). Consumption of alcohol is weakly associated with gastric cancer, and smokers have an increased risk generally. There is a small group of patients in whom hereditary factors are important.

Examination

General physical examination may be unremarkable. However, nutritional assessment is important. Advanced disease may be identified by the presence of an epigastric mass, nodes in the left supraclavicular fossa, the presence of ascites, or a pelvic mass palpable on rectal examination as a result of peritoneal spread of tumour.

Investigations

Contrast studies

Seldom used in the diagnosis and investigation of oesophageal tumours, but barium swallow may be used in the investigation of a patient with dysphagia.

Computed tomography (CT) scanning

Of value in oesophageal cancer for the detection of distant metastases, particularly liver and pulmonary metastases. It can detect tracheal or bronchial invasion in up to 90% of cases, and the identification of pleural and pericardial involvement is similar. It is less accurate in the detection of nodal metastases (70% accuracy) and assessment of the cardio-oesophageal area, and the presence of diaphragmatic involvement is less secure with CT scanning. In gastric cancer, overall detection rates of the primary tumour approach 90%, but requires a high-resolution scanner, and distension of the stomach with water and contrast. CT has an accuracy of 70% in detection of nodal metastases, and the detection of distant metastases is similar to oesophageal cancer.

Magnetic resonance imaging (MRI)

Provides similar results to CT scanning.

Endoscopy

Along with accompanying biopsy, endoscopy is an important part of the investigation of a patient with suspected oesophageal or gastric cancer.

For oesophageal cancer, 100% of early cancers can be diagnosed. The number of biopsies increases diagnostic accuracy. Advanced cancers can appear polypoidal, ulcerative or diffusely infiltrative. Barrett’s mucosa can also be identified, and multiple biopsies should be performed to identify areas of high-grade dysplasia.

For gastric cancer, endoscopy can identify the site, the nature and the degree of involvement and the dimensions of the tumour. Biopsy can identify the tumour type, as the diffuse type of tumour (secreting mucin, and with no gland formation) has a worse prognosis than the intestinal tumour (which forms glandular structures). Chronic gastritis can also be identified.

Bronchoscopy

An important additional investigation in upper and middle-third oesophageal cancer to assess for evidence of invasion. Endoscopic ultrasound may be able to assess this.

Endoscopic ultrasound (EUS)

A useful tool in the preoperative staging of both oesophageal and gastric cancers, and its use provides superior results to CT in the local staging of these tumours. EUS can identify involved lymph nodes in up to 90% of cases, but is less accurate in early stage disease. EUS has a central role in the initial anatomic staging of oesophageal cancer because of its high accuracy in determining the extent of locoregional disease. EUS is inaccurate for staging after radiation therapy and chemotherapy, but can be useful in assessing treatment response. For initial anatomic staging, EUS results have consistently shown more than 80% accuracy compared with surgical pathology for depth of tumour invasion. Accuracy increases with higher stage, and is >90% for T3 cancer. EUS results have shown accuracy in the range of 75% for initial staging of regional lymph nodes. EUS has been invariably more accurate than computed tomography for tumour (T) and lymph node (N) staging. EUS is limited for staging distant metastases (M), and therefore EUS is usually performed after assessment for distant metastases by CT scanning or positron emission tomography. Pathologic staging can be achieved at EUS using fine-needle aspiration (FNA) to obtain cytology from suspect lymph nodes. FNA has had greatest efficacy in confirming coeliac axis lymph node metastases with more than 90% accuracy. EUS is inaccurate for staging after radiation and chemotherapy because of its inability to distinguish inflammation and fibrosis from residual cancer, but a decrease in tumour cross-sectional area or diameter of more than 50% has been found to correlate with treatment response. Stricture due to tumour precludes full assessment of tumour size and nodal status, and dilatation to allow passage of the probe results in a high perforation rate. EUS offers the best preoperative local gastric cancer staging, with accuracies in T and N staging of approximately 78% and 70%, respectively. Although EUS is not suitable for diagnosing distant metastases, it may be more useful in detecting ascites due to the close proximity to the peritoneum.

Laparoscopy

Can be performed as a separate procedure prior to final choice of therapy. Laparoscopy can identify occult peritoneal and hepatic disease in up to 25% of potentially resectable gastric cancers, thus allowing informed decision making in relation to a more significant abdominal operation. It also allows consideration of other palliative modalities.

Laparoscopic ultrasound

May combine the benefits of detection of occult metastases (laparoscopy) and nodal status (EUS). Resectability (up to 100%), TNM staging (82% accurate), nodal status (92%), T stage (96%), M stage (89%) are all significantly improved over laparoscopy alone for oesophagogastric tumours, and is as accurate as EUS. Laparoscopic ultrasound may be the optimal preoperative staging tool, and may have a complementary role to EUS in oesophageal cancer.

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