Introduction

Symptoms of the upper gastrointestinal tract are very common. The prevalence of upper gastrointestinal symptoms in Western populations is estimated to be 20–40%. The majority of people will have no clinically significant or benign causes. A small proportion (2%) will be caused by upper gastrointestinal cancers. It is estimated that approximately 3–4% of a general practitioner’s workload will consist of patients with upper gastrointestinal complaints but, on average, a single general practitioner will only see one patient with esophageal cancer in 5 years, one gastric cancer in 3 years and one pancreatic cancer in 4 years. It is therefore important to maximize the yield of investigations by identifying those patients who are more likely to have pathology. In 2002, guidelines were issued by The British Society of Gastroenterology with this aim. In this chapter, we will discuss commonly encountered symptomatology and investigations.

Upper gastrointestinal investigations

The mainstay of upper gastrointestinal investigations comprises: endoscopic, including gastroscopy, endoscopic retrograde cholangiopancreatography (ERCP); radiologic, including contrast swallow studies, ultrasonography, computed tomography, magnetic resonance imaging, positron emission tomography; and a combination of both endoscopic and radiologic in the form of endoscopic ultrasonography.

Dyspepsia

Dyspepsia is a general term used to refer to upper abdominal (including retrosternal) pain. This is a general non-specific term and is sometimes interchanged with indigestion. Dyspepsia is very common and is estimated to affect some 25% of the population. Using dyspepsia in its broadest sense, its cause may be functional, ulcer, gastroesophageal reflux disease, gallstones and cancer. Functional refers to failure to function normally related to either the muscles of the organ or the nerves that control the organ. The symptoms of dyspepsia are varied and, in 2006, an updated symptom criteria was proposed further to define this. The Rome III committee was published and the definition of dyspepsia was again refined (Tack et al., 2006). They have defined functional dyspepsia as symptoms originating in the gastroduodenal region in the absence of any organic, systemic or metabolic disease that is likely to explain these symptoms. This is further refined into two new symptom classes: epigastric pain syndrome, referring to epigastric pain/burning and postprandial distress syndrome, which is meal-induced symptoms.

The Rome III criteria are, in reality, of little use to clinicians in everyday practice. The management of such a patient has been rationalized by the National Institute of Clinical Excellence (NICE). Briefly, the initial management should focus upon excluding causes of dyspepsia from medications, excluding alarm symptoms and Helicobacter pylori (H. pylori) infection. A short course of proton pump inhibitor may be prescribed and the effect monitored. Persistence of symptoms or appearance of alarm symptoms will require urgent endoscopic investigation (British Society of Gastroenterology, 2004).

NICE recommends that:

Alarm (RED flag) symptoms

The British Society of Gastroenterology (2005) published guidelines for referral for suspected upper gastrointestinal cancers. In that, they listed:

Ninety-nine percent of upper gastrointestinal cancers occur over the age 45 years with 90% of gastric cancers occurring above 55 years. The chance of a dyspeptic patient age under 55 years of having a cancer is one in a million.

Chronic gastrointestinal bleeding may result from the upper and lower gastrointestinal tract (see Chapter 10). Chronic gastrointestinal tract bleeding may result in normocytic or microcytic anemia. Patients who have upper gastrointestinal bleeding may complain of black offensive smelling stool (melena). Iron deficient anemia is commonly found. It has been estimated that gastrointestinal cancers are found in approximately 10% of patients presenting with iron deficient anemia and approximately 4% are from the upper gastrointestinal tract (James et al., 2005; Killip et al., 2007). Unintentional weight loss is defined as decrease of 5% or more in body weight within a 6–12 month period. It may be caused by organic, psychosocial and unknown etiologies. Of these, approximately 25% are caused by malignancies (Lankisch et al., 2001; Metalidis et al., 2008). Weight loss in gastrointestinal malignancy may be caused by reduced nutrient intake caused by physical obstruction of food intake (dysphagia and vomiting), anorexia, early satiety and other tumor hormonal factors.

Dysphagia is difficulty in swallowing and may be further refined to impedance in swallowing solids and liquid (see Chapter 7). Though it may be difficult, dysphagia should be distinguished from globus sensation, which is a feeling of having a lump in the throat, which is unrelated to swallowing and occurs without impaired transport.

Dysphagia may occur in esophageal tumors (malignant and benign), pharyngeal pouch, peptic stricture, pharyngeal web, connective tissue diseases (scleroderma), achalasia, diffuse esophageal spasm, extrinsic compression from enlarged left atrium, aortic aneurysm, aberrant subclavian artery, retrosternal thyroid, cervical bony exostosis and thoracic tumor.

Vomiting may occur in complete or severe dysphagia and in gastric outlet obstructions. Gastric outlet obstruction may be caused by functional (e.g. diabetic gastroparesis) or mechanical (gastric cancers and peptic ulceration) conditions. Early satiety and fullness are common in gastric and head of pancreas cancers. About 50–60% of gastric outlet obstruction is caused by malignancy with 50% of these from pancreatic cancers (Kaw et al., 2003). Patients may complain of a mass in the epigastrium from a distended stomach or from the cancer itself.

Peptic ulcers

Peptic ulcers include gastric and duodenal ulcers. This is characterized by a disruption of the mucosa of the gastrointestinal tract and is a result of the imbalance between mucosal defense (water-insoluble mucous barrier, local production of bicarbonate) and offensive factors (increased gastric acid secretion, H. pylori infection, non-steroidal anti-inflammatory drugs (NSAIDs) and mucosal ischemia).

Helicobacter pylori is a gram-negative urease-producing spirochete that was linked to gastric ulcers and gastritis in 1983. The urease neutralizes the acidic environment and causes mucosal inflammation, ulceration as well as increasing gastric acid production. As a result the duodenum is exposed to higher levels of acid.

Symptoms of peptic ulcer disease are variable but may include nausea, anorexia, weight loss, hunger pain, melena, upper abdominal pain that may be improved (duodenal) or worsened (gastric) with food ingestion and antacids. The pain of peptic ulcer disease correlates poorly with the severity of active ulceration or gastritis. Complications of peptic ulcers include bleeding/hemorrhage, perforation and obstruction. Investigations of choice for peptic ulcer disease include gastroscopy that will allow for diagnosis as well as obtaining tissue for histological differentiation of benign ulcers from malignant gastric cancers. Other investigations that are acceptable, especially in elderly and frail individuals, include double contrast study, although it may not detect small ulcers. As well as guidance given for treatment of dyspepsia (see dyspepsia), NICE recommends:

Diarrhea

Diarrhea is defined as frequent passage of watery stools. Diarrhea may be acute or chronic (lasting more than 2 weeks) (Table 5.1). Nausea, vomiting, anorexia, weight loss, passing blood per rectum, dehydration, abdominal pain and fever may also accompany diarrhea.

Table 5.1 Common causes of diarrhoea

Causes	Investigations
Infectious diarrhea Bacterial Viral Parasites Antibiotics

Stool culture within 3 days of onset Thyroid function test, random, fasting glucose, glucose tolerance test Irritable bowel disease Dumping syndrome Contrast study, blood glucose

Investigations are usually required in severe and chronic diarrhea. The type of investigation is guided by the medical history and suspected cause of the diarrhea.

Infectious diarrhea: the most common cause of diarrhea is infective which may be bacterial (salmonella, staphylococci, Escherichia coli, Clostridium difficile), viral (Norovirus, rotavirus, Norwalk virus, cytomegalovirus) and less common in developed countries, parasites (Giardia lamblia, Entamoeba histolytica and Cryptosporidium). The majority of diarrhea is self-containing and resolves after a few days.

The value of stool culture is limited. A large study of 59,500 specimens only yielded a positive result in 6.4% of cases. A timely stool culture is crucial to confirming or excluding infective causes (<3 days infective, <4 days parasitic from onset) (Valenstein et al., 1996).

Food intolerance: blood and breath tests may be used for food intolerance in addition to gastroscopy and radiological studies.

Celiac disease is a common condition, affecting about 1 in 100–300 adults in the UK, that is caused by intolerance to gluten. Anti-endomysial, anti-gliadin and anti-tissue transglutaminase antibodies as well as IgG and IgA levels are used for detecting celiac disease before gastroscopy to obtain tissue biopsy for confirmation which remains as the gold standard for confirming celiac disease. Radiological studies (abdominal CT, small bowel enema) for celiac disease are used for detecting complications of the disease (intussusception (usually intermittent), ulcerative jejunitis, osteomalacia, cavitating lymph node syndrome and an increased risk of malignancies such as lymphoma, adenocarcinoma and squamous cell carcinoma) rather than as a diagnostic tool (Buckley et al., 2007).

Lactose intolerance is the inability of the body to digest lactose, which is a sugar commonly found in milk and diary products. A degree of lactose intolerance is found in approximately 75% of the population. Hydrogen breath test, lactose/milk intolerance test, small bowel biopsy and stool acidity tests are used to detect lactose intolerance. Radiology does not have much role in managing this condition.

Inflammatory bowel disease: Crohn’s and ulcerative colitis are discussed in Chapter 16. Investigations include gastroscopy, colonoscopy, enteroscopy, small bowel enema and abdominal CT scan.

Pancreatic insufficiency: pancreatic insufficiency is caused by insufficient exocrine pancreatic function, in other words, the inability of the pancreas to produce adequate digestive enzymes. The causes of pancreatic insufficiency include cystic fibrosis, chronic pancreatitis, pancreatic surgery and pancreatic cancer.

Investigations of pancreatic insufficiency include radiological imaging of the pancreas (ultrasound, CT, MRI scans, endoscopic retrograde cholangiopancreatography). The function of the pancreas may be assessed by fecal fat, fecal elastase, pancreolauryl test.

Metabolic: thyrotoxicosis (hyperthyroidism) may cause diarrhea. The patient will often display symptoms of anxiety, raised heart rate, history of weight loss. Investigations include a simple blood test for thyroid function.

Diabetes can cause autonomic neuropathy of the gastrointestinal tract resulting in diabetic diarrhea. Other symptoms of diabetic diarrhea include steatorrhea (pale fatty stool) and malabsorption. Diagnosis of diabetic diarrhea is by exclusion and investigations include gastroscopy, colonoscopy, small bowel enema and hydrogen breath test.

Dumping syndrome: this syndrome is a collection of gastrointestinal and systemic symptoms. It can be caused by any surgery (vagotomy, pyloroplasty, gastrojejunostomy and laparoscopic Nissan fundoplication) to the stomach that affects the delivery of food into the small intestines.

Investigations for dumping syndrome include gastroscopy and barium swallow and follow through.

Jaundice

Jaundice is characterized by the skin and sclera turning yellow. This is caused by increased level of bilirubin in the blood. Patients may complain of darkened urine in obstructive jaundice. The causes of jaundice can be pre-hepatic (hemolysis), hepatic (hepatitis, liver cirrhosis) and post-hepatic (obstructive jaundice from gallstones, cholangiocarcinoma, pancreatic cancer).

Investigation for jaundice is dependent on the cause and will include blood tests to check for liver function, anemia from hemolysis, malaria, sickle cell anemia, spherocytosis, hepatitis screen, autoimmune antibodies, ceruloplasmin, transferritin. Radiological investigations include transabdominal and endoscopic ultrasound, CT, MRI scan, fibro scan and liver biopsy.

Nausea and vomiting

Nausea and vomiting are symptoms that can accompany many conditions (Table 5.2). It is important to take a detailed medical history that will help direct the investigations. In general, vomitus that does not contain bile is likely to be but not always of less serious nature (central causes). Vomitus that contains bile is taken to be more significant and may suggest an obstruction somewhere beyond the second part of the duodenum (bowel obstruction, pancreatic cancer).

Table 5.2 Common causes of nausea and vomiting

Causes	Investigations
Acute gastritis • Infections: bacterial, viral and parasitic infections of the gastrointestinal tract • Peptic ulcer disease

CT scan of brain if appropriate  

Investigations may include blood tests, stool culture, abdominal x-rays, ultrasound, contrast gastrointestinal studies, CT/MRI scans and endoscopy.