Chronic or Recurrent Abdominal PainCHAPTER 1

Based on the UK general practitioner studies, the UK general practitioner with an average patient list will encounter over 25 new cases of functional bowel problems compared to a probability of 1 incidental case of colorectal cancer and the average general practitioner will encounter inflammatory bowel disease like a new case of Crohn's disease once every 7 years or more. Identifying the individuals who are likely to have an organic disease rather than a functional disease is therefore very important. Probably the single most important consideration is the patient's age. It is unsafe to label any chronic abdominal pain developing for the first time in a patient over 40 years of age as functional without further investigation. If the patient is under 40 years of age, then it is important to try to make a positive diagnosis of functional pain, such as irritable bowel syndrome (IBS), from the history and ask specific questions if the answers are not provided spontaneously. These questions include:

A positive answer to the above questions usually suggests functional abdominal pain. Conversely, the pain is usually more likely to be organic and warrants further investigation regardless of the age if:

Thorough general examination including rectal examination and a few blood tests should usually suffice. A blood test should include full blood count, erythrocyte sedimentation rate (ESR) or plasma viscosity and liver function tests (LFTs) as found in many automated serum profiles. Even if these are normal one can miss inflammatory bowel diseases, particularly Crohn's disease, especially if the patient comes from a high-prevalence country. Serum acute phase reactant test like C-reactive protein (CRP) can also be quite useful as it does reflect an inflammatory process. More recently, fecal calprotectin has been shown to be useful in differentiating between inflammatory bowel conditions and those with normal or IBS (Fig. 1.1). The prevalence of the conditions and incidental cases per year, per general practitioner, is given in Table 1.1.

A simple diagnostic algorithm to differentiate between IBS and other causes of abdominal pain is illustrated in Figure 1.2. When a physician encounters a patient with abdominal pain with some bowel symptoms, it is important to try to make a positive diagnosis of IBS early. This will reassure the patient, enable early implementation of treatments and prevent unnecessary and painful investigations.

Symptoms that should concern the physician are:

If they do not have these symptoms, then the physician should proceed to obtain fecal calprotectin and, if that is negative, a firm diagnosis of IBS can be made. For the case of predominant diarrhea, refer to Chapter 3 for reaching a diagnosis.

Patients taking nonsteroidal anti-inflammatory drugs (NSAIDs) may have duodenal ulcer disease with little or no symptoms at all, probably due to the analgesic effects of non-steroidal drugs themselves. As a result, they may present late and perhaps with a complication like bleeding or perforation. A history of drug use is important, therefore as part of the work-up for these patients.

The best way of diagnosing patients with upper gastrointestinal (GI) abdominal pain is to perform an endoscopy (Figs. 1.3 and 1.4). In patients under the age of 40 years, it is not unreasonable to carry out non-invasive investigations before considering an endoscopy. This could be a Helicobacter pylori fecal antigen test which is a simple and low-cost investigation. If the patient is young and presents with predominantly dyspeptic symptoms, it is also not unreasonable to give a trial of a proton pump inhibitor (PPI) like lansoprazole or omeprazole to see if it alleviates the symptoms. However, in areas where there is a high incidence of gastric cancer, it is not unreasonable to perform a prompt endoscopy in order to detect early cases of gastric cancer.

Duodenal ulcer disease is associated with Helicobacter infection in the majority of patients without a history of non-steroidal use. The easiest and cheapest method of detecting H. pylori with a high degree of sensitivity and specificity is the fecal antigen test. However, other tests such as blood serum antigen testing and urea-based breath tests are also available.

Endoscopy remains the investigation of choice when there is a suspicion of gastroduodenal disease. A well performed endoscopy can be done without sedation or under light sedation and is usually very well tolerated. This would also be able to pick up suspicious pathology like early gastric cancer. If the endoscopist encounters an ulcer in the stomach, it would be mandatory to biopsy it and also to review it at an interval of 6–8 weeks after treatment to make sure it is healed completely.

A diagnosis of Zollinger–Ellison syndrome (gastrin-producing tumor) should be considered if there are extensive multiple duodenal ulcers or patients with ulcers resistant to treatment with PPIs, patients with extensive ulcers who are Helicobacter negative or continue to have ulcers after 6Helicobacter eradication. Investigations for Zollinger–Ellison syndrome include a fasting gastrin level. Sometimes calcium levels may also be elevated in MEN1 (Multiple Endocrine Neoplasia Type 1) syndrome. These patients have tumors in the 3 Ps—pituitary (e.g. prolactinoma), pancreas (gastrinoma), and parathyroid. The gastrinomas tend to be multiple. Imaging with computed tomography (CT) scanning is often sufficient to locate the lesions but other modalities like magnetic resonance imaging (MRI) can also be very useful. Transabdominal ultrasound may even be sufficient in some cases of locating a lesion. Pancreatic gastrinomas can also be localized using endoscopic ultrasonography, which has a higher sensitivity and specificity for pancreatic and duodenal gastrinomas.

Gallstones can cause two varieties of pain. This may be due to inflammation or it could be due to stones or tumor that is obstructing the outflow of the gallbladder. Forcible contractions against such an obstruction would result in pain. Pain also occurs if the gallstones are impacted infundibulum or the neck of the gallbladder or if they are extruded into the common bile duct and can obstruct the common bile duct.

A typical feature of biliary pain is epigastric or right upper quadrant pain that often radiates to the back or to the right shoulder blade associated with nausea or flatulence. These symptoms mimic the pain of IBS or peptic ulcer disease or even cardiac ischemia. If examinations carried out at a time when the patient has symptoms, tenderness in the right upper quadrant may be a useful sign.

The pain of biliary colic can be quite characteristic. It is often very memorable, very severe, and it rises to a crescendo and plateaus for about 30 minutes or so before diminishing again. Patients may have episodes of these pains and may be able to recall the episodes quite succinctly. These characteristic symptoms would point to a biliary cause for the patient's pain. If the patient just complains of a vague, generalized pain in the right upper quadrant this is usually not caused by biliary colic and removal of the gallbladder with or without stones usually is unproductive.

When stones dislodge into the common bile duct, then abnormal liver function tests (LFTs) may result with or without a rise in serum bilirubin; but when obstruction gets complete, then jaundice is inevitable. Sometimes stones impacted in the neck of the gallbladder can cause local edema, which can compress on the common bile duct and cause a degree of jaundice or abnormal LFTs. This is sometimes referred to as Mirizzi's syndrome.

Pain of an inflamed gallbladder is usually a constant right upper quadrant pain and can be exquisitely tender on palpation.8

If other lesions are suspected, then a computed tomography (CT) scan would be a very useful investigation as it would likely image the pancreas rather better than an ultrasound scan. If stones in the common bile duct are suspected either from raised LFTs or if there is a dilated common bile duct without obvious stones, then it is reasonable to proceed to magnetic resonance cholangiopancreatography (MRCP), which is valuable in assessing the presence of common bile duct stones. The presence of common bile duct stones will require therapy with endoscopic retrograde cholangiography (ERCP) (Figs. 1.8 to 1.10).

When the pancreatic lesion is in the head of the pancreas, the patient often presents with jaundice as a result of obstruction of the common bile duct. Once again a CT scan is helpful in staging the disease and making a diagnosis. An endoscopic ultrasound is also very helpful in further staging of disease, especially when it is in the head or the neck of the pancreas. Lesions in the tail of the pancreas are less accessible to endoscopic ultrasound (Figs. 1.11 to 1.17).

In the older patient presenting with any of these symptoms, the principal condition to exclude is colonic neoplasia. Some form of imaging is therefore necessary in both groups of patients.

Colonoscopy is by far the best imaging modality as it would pick up any colonic neoplasia and the majority of patients with colonic or ileocolonic inflammatory bowel disease. A skillful colonoscopist should be able to enter the terminal ileum and assess the terminal ileum in over 90% of patients. Inflammatory changes in the colon are very common in patients with Crohn's disease, even in those with predominant ileal disease. If the patient is unable to have a colonoscopy for whatever reason, then the alternative is CT colography or MRI scanning. In patients where colon cancer is being suspected, particularly the older age group, CT colography can be a useful alternative to colonoscopy. It may be an alternative in individuals for whom colonoscopy is deemed too invasive, especially in the frail elderly patient. There are limitations to CT colography. Polypoidal lesions can be difficult to differentiate from particulate feces and it is clearly not possible to carry out biopsies and histological examination of any lesions seen. Often when 15a lesion is suspected or found the individual will need a colonoscopy eventually. There is also an issue of radiation exposure and therefore colonoscopy is still regarded as the investigation of choice. MRI scanning is also valuable. It is particularly useful in detecting small bowel Crohn's disease, especially in parts where the colonoscope is unable to reach. A modified way of performing an MRI with the ingestion of a polyethylene glycol drink allows imaging of the small bowel with contrast (magnetic resonance enterography; MRE). This will pick up areas of intestinal stenosis caused by inflammation and also fissures and ulcerations of the mucosa. MRE also gives a good impression of the thickness of the bowel, another indication of infiltrative or inflammatory condition. A standard CT of the abdomen is also a valuable investigation. It has the advantage of being somewhat cheaper than MRI and it can show quite a lot of detail. It will also show the presence of abscess formation or diverticular disease of the colon. Finally, if lymphoma is suspected, a CT scan of the abdomen would pick up associated lymphadenopathy, which usually is generalized and may be associated with splenic enlargement (Figs. 1.17 to 1.21).

Porphyria can cause abdominal pain. Acute intermittent porphyria, porphyria variegata but not porphyria cutanea tarda, can cause acute intermittent episodes of severe abdominal pain rather than chronic pain. There may be neurological complications such as behavioral disturbances, epilepsy, coma or peripheral neuropathy. During an acute attack of hyponatremia; hypertension and uremia are common. Other rare causes of abdominal pain include lead poisoning, C1 esterase inhibitor insufficiency, familial Mediterranean fever and neurological conditions like multiple sclerosis and peripheral neuropathy. Abdominal pain is also a common problem in patients with longstanding diabetes. They are at increased risk of gallstones, duodenal ulcer disease, intestinal vascular insufficiency and pancreatitis.

A high index of suspicion and the specific diagnostic test is required to make the correct diagnosis.

This definition is rather loose and all-encompassing and has since been replaced by Rome IV in 2017. NICE (National Institute of Clinical Excellence) offered an alternative, simpler definition that is more suitable for everyday clinical use and the definition is:

Abdominal pain/discomfort relieved by defecation or associated with altered stool frequency/form plus 2 or more of:

From a clinical point of view, the patients presenting with the classic pattern of abdominal pain associated with bloating and a change in bowel habit are usually easy to pick out and patients with predominant constipation or alternating constipation and diarrhea probably require no further investigation. However, patient with persistent diarrhea would probably benefit further investigation to detect cases of small intestinal bacterial overgrowth, bile salt diarrhea and microcytic/collagenous colitis.

The stool type correlates very well with gut motility and the Bristol Stool Chart has become a very useful visual aid in clinics for patients to point out which type of stools they have. Stool types 1 and 2 (Fig. 1.28) are associated with constipation and the gut transit is slow, whereas patients with Bristol types 6 and 7 have rapid gut transit and diarrhea.

In this group, only a simple noninvasive test is required. Blood tests including a full blood count, biochemistry, CRP and thyroid function test along with celiac antibodies can be carried out. Stool tests, including fecal calprotectin and culture if there is the reason to suspect an infective cause. If diarrhea is predominant, a hydrogen or methane breath test can be very helpful. This detects the presence of small bowel bacterial overgrowth that ferments glucose or lactulose and releases hydrogen or methane in the breath. The test is simple and relatively cost-effective. Fecal calprotectin or lactoferrin is emerging as a very helpful test in this situation. Calprotectin and lactoferrin are released by inflammatory cells into the GI tract and this is excreted in the feces and easily detected. When there is inflammation, the level of fecal calprotectin 25rises exponentially. Laboratory standards vary, but any fecal calprotectin over 50 µg/g of feces is usually indicative of possible inflammatory bowel disease. However, a negative calprotectin does not exclude other organic diseases or indeed Crohn's disease in remission. A simple algorithm is shown in Figure 1.2.

Often doubt still exists as to whether or not the patient has inflammatory bowel disease and probably the single most useful investigation in this situation is to perform a colonoscopy. For patients with diarrhea-predominant symptoms, inflammatory bowel disease can be difficult to exclude. Patients with microcytic and collagenous colitis can be very difficult to diagnose without endoscopic examination and may have negative fecal calprotectin and ultimately can only be diagnosed with biopsies, particularly of the right colon.

Having established a rapport, the physician should look at exploring some of the triggers. If there is evidence of an infective trigger, then probiotics may be proffered although clinical trial evidence for its use is sketchy. If there is a degree of stress or anxiety involved, that should be addressed at a suitable time. Other psychological treatments like hypnotherapy and counseling have a place if available.

Newer drugs have been recently evaluated for use in IBS with constipation. For IBS-C linaclotide have recently been introduced. A longer discussion of these drugs on constipation is in the Chapter 4. For IBS-D, symptomatic treatment with loperamide is helpful and new agents like eluxadoline have been recently approved for this indication. Rifaximin, a poorly absorbed antibiotic, has also been approved for IBS-D (see Chapter 3).

Patients with evidence or suspicion of bile salt malabsorption could be given a trial with cholestyramine. Bile excretion is maximal in mornings, so this is best given first thing in the morning, 30 minutes before breakfast. If there is evidence of small intestinal bacterial overgrowth, antibiotic therapy, notably with rifaximin, could be given.

Drugs like the anti-inflammatory drugs and aspirin cause ulceration either by direct toxic effects or inhibit prostaglandin synthesis by binding on cyclo-oxygenase (COX) active site (specifically COX-1). Aspirin even in low doses can cause ulceration by direct toxic chemical effects on the mucosa itself. Nonsteroidals drugs, however, tend to act by inhibiting prostaglandin synthesis. Prostaglandin depletion causes an increase in acid secretion, 28decreased mucin production and a decrease in bicarbonate secretions, all factors vital in promoting ulcer formation. Prostaglandin is also important in epithelial cell healing and therefore nonsteroidal drugs also reduce the ability of the mucosa to repair itself. Additionally, the analgesic effects of non-steroidal drugs may account for the fact that many nonsteroidal-induced duodenal ulcer disease remain silent and may not present until bleeding or perforation occurs (Fig. 1.29).

The infection is probably acquired during childhood and spreads in areas and times of overcrowding. Initially, the bacterium tends to inhabit the antrum of the stomach and over time tend to migrate proximally. Apart from duodenal ulcer disease, H. pylori infection is credited to cause gastric ulcers, MALT lymphomas and gastric cancer. It is still not understood as to how the bacterium can cause the diverse pathology and yet, in a large number of individuals, it causes no symptoms or pathology at all. It is likely to be a combination of bacterial and host factors. The bacteria may have genetic determinants that result in increased pathogenicity. This includes 29its ability to produce certain enzymes like VacA and CagA or may have adhesins which facilitate attachment of the bacteria to the gastric epithelial cells. Amongst host factors may be the subject's ability to mount an inflammatory response and the specific site of the stomach where the bacteria tend to colonize.

Patients who predominantly have antral inflammation would lead the antral G cells to produce high levels of gastrin via the loss of negative inhibition from the D cells in the antrum. The result is an elevated gastrin level that stimulates the acid secreting parietal cell to secrete more acid. Patients who have predominantly body and fundus infection with H. pylori may find that the parietal cells themselves get affected and acid level output may actually be reduced. This may lead, in the long term, to chronic atrophic gastritis eventually leading to intestinal metaplasia, dysplasia and leading to gastric cancer. In the majority of patients with pangastritis, the infection tends to be non-pathogenic and therefore the bacterium inhabits the individual without producing any symptoms or disease (Fig. 1.30).

Inhibitors of the proton pump include omeprazole, esomeprazole, lansoprazole, pantoprazole and rabeprazole. Thus, almost complete blockage of acid secretion is the result. These drugs also have a long biological life as the inhibition is irreversible and parietal cells have to manufacture new proton pumps to replace those blocked. Ranitidine in clinical trials has shown to heal up to 70% of duodenal ulcers at 8 weeks whereas PPIs would heal duodenal ulcers at > 90% at 8 weeks. However, unless the underlying cause for the ulcers (e.g. H. pylori and nonsteroidal drugs) is removed then the ulcers would tend to recur (Fig. 1.31).

When widespread duodenal inflammation occurs, it is also important to consider Crohn's disease; celiac disease; Whipple's disease and small bowel lymphoma. Biopsies would be indicated if the endoscopist is unsure of the exact pathology or if these conditions are suspected. Usually, however, the inflammation is mild, confined to the first part of duodenum and is usually of little consequence to patients.

When endoscopy is carried out it is usually normal and is thus regarded as a functional condition. There is evidence of poor pyloric relaxation and gastric emptying and there is also evidence of visceral hypersensitivity with pain or intolerance when the stomach is distended with fluid.

The management of functional dyspepsia includes the following:

Gastrin is produced by the G cells of the gastric antrum. In Zollinger–Ellison syndrome, excessive gastrin is produced by non-beta islet cell tumors of the pancreas or duodenum. This is not under the natural feedback mechanism and leads to constant over stimulation of the parietal cells that leads to overproduction of acid. This results in hypertrophy of the gastric body and a high basal acid output. The acid is dumped into the duodenum and upper duodenum and causes ulceration.

The tumor is malignant in about 65% of patients and about 25% of tumors are sited in duodenal wall and may be very tiny and difficult to diagnose. 34However, the majority of the tumors will be found in the duodenum or the neck of the pancreas or even the porta hepatis.

Acid also inactivates pancreatic lipases and results in fat malabsorption. Diarrhea is therefore a very common symptom along with the classic symptoms of duodenal ulceration.

Imaging with CT scan would be necessary to locate the tumor but it is only possible to locate the tumor in 50% of the patients. Endoscopic ultrasound can also be very useful. Frequently tumors are <1 cm and easily missed on scanning. Somatostatin receptor scintigraphy (octreotide scan) is the best imaging modality. It uses radiolabeled somatostatin analog that binds to the receptors found on these tumors (Fig. 1.33). Finally, endoscopy which shows unusually severe ulceration of duodenum should alert the clinician to consider this diagnosis.

Avoidance of nonsteroidal agents would be important in patients who have nonsteroidal-induced gastric ulcers. Aspirin and antiplatelet drugs like clopidogrel should be reviewed. However, these are often prescribed for major cerebrovascular and cardiovascular indications like stroke and ischemic heart disease. The morbidity and mortality from these conditions may outweigh the risks of the gastric ulcers and therefore coprescription with PPI and aspirin together is acceptable and often results in lower overall morbidity and mortality.

Probably the best way of classifying gastritis is probably by its etiological origin.

Helicobacter pylori pathogenicity is decided by certain inherent virulence factors in the bacterium. Strains that produce a protein CagA associated with greater risk of developing gastric cancers and peptic ulcers.

Some patients develop a multifocal atrophic gastritis pattern where the infection of the corpus of the stomach eventually leads to a pattern of gastric atrophy with loss of gastric glands and eventually replacement of gastric glands by intestinal-type mucosa (intestinal metaplasia). This will eventually develop into dysplasia and gastric cancer. Because of gastric atrophy, the acid levels tend to fall and carcinogenic agents such as nitrosamine are not neutralized by acid.

The majority of patients with H. pylori-associated chronic gastritis, however, remain asymptomatic. Only a small number will develop duodenal ulcer disease and gastric cancer (Figs. 1.35 and 1.36).

Atrophic gastritis can be as a result of H. pylori infection when the H. pylori causes a pangastritis or a corpus gastritis. Thus, infection must be excluded by fecal antigen testing or any other readily available tests.

Atrophic gastritis may result in lower gastric acid production and may result in increased risk of gastric cancer. Atrophy of parietal cells also results in reduced production of B12 and development of B12 deficiency and pernicious anemia.

In terms of diagnosis, the endoscopic appearance of an atrophic stomach can be quite obvious with lack of rugal folds and biopsies would also be helpful in making the diagnosis.

Eosinophilic infiltration of gastric mucosa would result in eosinophilic gastritis. This condition is rare although it is increasingly being diagnosed. There may be a peripheral blood eosinophilia and they are sometimes associated with asthma and other allergic conditions. Patients may present with abdominal pain, fever, diarrhea or even ascites. Large antral folds may simulate other infiltrative processes like lymphoma and therefore biopsies are usually required to make a diagnosis. Patients may present with gastric outlet obstruction due to edema of the pylorus and infiltration of the antrum of the stomach (Fig. 1.37).

A palpable mass may be found on examination. Signs of tumor spread may also be presenting features. Prominent left supraclavicular lymph node (Virchow's node) may be a sign of metastatic spread of gastric cancer and is also the most common sign of metastatic disease. When there are hepatic metastases then the liver may be often palpable and ascites may also be detected when there is peritoneal carcinomatosis.

The imaging modalities required to adequately stage patients include:

Neoadjuvant chemotherapy refers to chemotherapy given before surgery to downstage the tumor. This is given in patients with bowel T3 or T4 tumors or patients with perigastric nodes.

Adjuvant chemotherapy refers to chemotherapy given along with surgery. The aim of adjuvant chemotherapy is to improve survival by eliminating any residual tumor after surgery.

The exact treatment protocol for each individual patient is usually discussed at the multidisciplinary team meeting where the imaging, histology and overall patient fitness are discussed. If the patient is fit for surgery, then every attempt is made to improve surgical outcome. Best treatments are still a subject for research and patients should be considered for entering many of the clinical trials that are currently running.

True adenomas of the stomach are relatively rare, occurring in about 5% of gastric polyps. They have a similar premalignant potential as colonic adenomas. Hence, they are best removed endoscopically if possible. It may be difficult endoscopically to decide the nature of the polyps then biopsies are best performed to establish diagnosis.

Other polyps that may be encountered in the stomach include hamartomatous polyps found in polyposis syndromes such as Peutz–Jeghers. Also, quite rare are gastric carcinoids. Four types of gastric carcinoids have been identified.49

Other lesions that look like polyps include gastrointestinal stromal tumors (GIST) (Fig. 1.52). These may be asymptomatic and may look like an elevated umbilical lesion in the stomach and are usually solitary. Occasionally, they might cause complications like bleeding and may undergo malignant transformation. In general, if they are <2 cm surveillance is probably not necessary. If they are >2 cm then it is worth considering EUS followed by surgery if it is judged to have malignant features. If in doubt, surgical excision should be considered.

Family history and genetics play an important part as does obesity itself. Curiously, rapid weight loss is a risk factor of gallstone formation and one of the complications of bariatric surgical operations. Other risk factors include diabetes, liver disease and Crohn's disease. Pigment stones are more likely in patients with hemolytic anemia from any cause. Drugs such as octreotide are also known to promote formation of gallstones. This may be due to its effects on gallbladder motility and increasing the chance of gallbladder stasis. Gallstone formation may be also a complication of total parenteral nutrition. This is probably due to its effects of causing biliary stasis. Surgical removal of terminal ileum will also affect enterohepatic circulation of bile acids and promote the formation of gallstones.

The mainstay of treatment is laparoscopic cholecystectomy. In expert hands, conversion rate to open cholecystectomy is usually <2% and duct injuries <0.1%. The main complications are bile leak, hemorrhage and retained stones.

For patients with previous cholecystitis, cholangitis or pancreatitis, risk of recurrence is high and therefore cholecystectomy is recommended. 52If the LFTs are abnormal or there is dilatation of the common bile duct on ultrasound, then an MRCP is recommended before embarking on surgery to ensure that there are no stones in the common bile duct (Fig. 1.9). Stones in the common bile duct can be removed by ERCP and that should be performed prior to surgery (Fig. 1.10).