Tests to estimate nutritional status

Nutritional assessment helps to identify patients who are more likely to develop complications from their malnutrition and, hence, likely to benefit from supportive nutritional therapy. Assessment can be either clinical or based on laboratory tests and measurements.

Calculate the BMI (Box 17.2). Other anthropometric measurements include triceps skin-fold thickness and mid-arm muscle circumference to assess the fat reserve and the muscle mass of the body, respectively. These quantitative measurements are useful for follow-up of nutritional status.

The subjective global assessment is based on the history and clinical findings. The degree of recent weight loss, dietary alterations, symptoms, the level of physical activity and stress due to illness (metabolic demand) is gauged from the history. Examination subjectively assesses the amount of fat reserve, muscle mass and oedema or ascites. Patients are then classified into one of three groups:

Laboratory tests that detect decreases in serum albumin or lymphocyte count (under 1.5 × 10⁹/L (under 1500/mm³)) are crude but helpful estimates of nutritional status. Estimation of proteins with a shorter half-life, such as transferrin or prealbumin, should be undertaken if enteral or parenteral nutrition is being considered. Vitamin levels (e.g. fat-soluble vitamins A, D and K) need to be checked in patients with suspected severe malabsorption (e.g. pancreatic insufficiency).

To determine adequate protein intake, nitrogen balance can be assessed by estimating the protein intake and urinary urea nitrogen excretion. To assess adequate caloric intake, energy expenditure can be calculated using the Harris-Benedict equation, if weight, height and age are known. To determine lean body mass and total body fat, body composition can be simply measured using bioelectrical impedance.

The prognostic nutritional index predicts the likelihood of developing postoperative complications in patients undergoing gastrointestinal surgery. It is based on a simple linear equation incorporating measurements of serum proteins (albumin and transferrin concentration), subcutaneous fat (triceps skin fold), and immunologic function (delayed skin hypersensitivity).

In the elderly, the mini-nutritional assessment is a valid tool that allows subdivision of patients into nourished, malnourished or at risk of malnutrition (Fig 17.1).

Table 17.2 Clinical findings associated with vitamin and mineral deficiencies

Tests aimed at detecting the cause

Diagnostic tests can be arbitrarily classified into those of a screening nature and those that target specific abnormalities detected by the history, physical examination or initial screening test results (Table 17.3). The tests are most successful in finding the cause when they are directed by the history and examination findings.

Table 17.3 Investigations for weight loss and examples of diseases to consider

Routine tests are inexpensive, and may help to identify the basic nature of the problem. A full blood count can detect evidence of iron deficiency anaemia, which may suggest blood loss from a gastrointestinal tract cancer. A high erythrocyte sedimentation rate or C-reactive protein may suggest inflammation or malignancy. Electrolyte and creatinine tests can identify chronic kidney disease as a cause of anorexia. Liver function tests can be helpful (e.g. elevated transaminase levels in hepatitis, obstructive jaundice due to pancreatic cancer or hypoalbuminaemia in malignancy or chronic liver disease). A serum calcium may detect hypercalcaemia caused by a malignancy. A bedside urine analysis may detect proteinuria (e.g. nephrotic syndrome) or haematuria. In the absence of infection or stones, persistent haematuria may indicate renal or bladder cancer. A positive result of a stool occult blood test may indicate colorectal neoplasia or inflammatory bowel disease, but this test has low sensitivity and specificity and is less often done (Ch 10). If malabsorption is suspected, then an appropriate work-up should be done (Ch 14). A thyroid-stimulating hormone test will detect hyperthyroidism and fasting blood sugar level test, diabetes mellitus. Tumour markers may occasionally help point towards a correct diagnosis in difficult cases but are of most use in following response to treatment (Box 17.3).

A chest x-ray examination is relatively inexpensive and an adjunct to the clinical examination. It is mandatory in the presence of pulmonary symptoms (e.g. to detect pulmonary tuberculosis or primary lung cancer) or if routine tests are unhelpful. A silent mass lesion, infiltrative process or lymphadenopathy may be detected on the chest x-ray film.

CT scans of the chest and abdomen provide excellent anatomical definition and objective assessment which is not operator dependent. They are extremely useful for defining mediastinal and retroperitoneal pathologies. Mediastinal widening seen on chest x-ray films in small cell lung cancer, lymphoma or thymoma can be delineated further with a chest CT scan. Similarly, metastatic lymph notes in the mesentery or in the retroperitoneum, or organomegaly detected on clinical examination can be accurately defined by an abdominal CT scan. Although CT should be reserved for localising a suspected lesion, this test is increasingly used for screening when no diagnosis is forthcoming. Ultrasound examination can provide valuable information about biliary anatomy or pelvic pathology (Ch 19). Mammography should be done in women if breast cancer is a consideration.

Gastroscopy and colonoscopy have replaced barium examination as the gold standard for visualising the upper and lower gastrointestinal tract. In patients with altered bowel habits or microcytic anaemia thought to be due to chronic gastrointestinal blood loss, endoscopy is the procedure of choice for detection of underlying pathology (e.g. gastric or colorectal cancer). Barium examinations still have a role to play in screening the small bowel (e.g. Crohn’s disease). Fine needle aspirations are useful for pathological confirmation of suspected lesions in organs such as the liver.

Test yield

Evaluation will reveal a cause for weight loss in 75% of cases. The most common causes are depression and cancer. In one-quarter of patients, despite detailed examination and exhaustive tests, the aetiology remains elusive. In such cases, it is prudent to adopt a wait-and-see approach since the diagnosis may become obvious within the next 6–12 months.

Pathogenesis

The exact aetiopathogenesis is unclear. It is rare before age 45 years and is more common in men and people of African descent. Increasing age (over 60 years) is a risk factor. Chronic pancreatitis and hereditary chronic pancreatitis (autosomal dominant due to a mutation in the cationic trypsinogen gene (PRSS1), Ch 6), and some familial cancer syndromes (e.g. Peutz-Jeghers syndrome) are of established importance. Smoking, diabetes mellitus, obesity, increased dietary fat, partial gastrectomy and Helicobacter pylori are also risk factors. There is no convincing evidence that coffee intake is a causal factor.

Clinical features

It usually manifests in elderly people and, unfortunately, often at an advanced stage. The initial symptoms and signs can be non-specific, but anorexia, weight loss and upper abdominal pain are common features.

Pain occurs in 75% of patients and weight loss is present in almost all patients. The pain is usually an epigastric dull ache, which may radiate through to the back. Weight loss is primarily due to anorexia, although malabsorption may also contribute. Gastric outlet obstruction with vomiting may occur. With the exception of jaundice, other symptoms are often insidious and delay diagnosis.

Jaundice due to biliary obstruction is found in the majority of patients with cancer of the pancreatic head. Pruritus is often associated. The gall bladder is usually enlarged in patients with cancer of the pancreatic head, but is impalpable in more than 50% (Courvoisier’s law: if the gall bladder is enlarged and the patient is jaundiced, the cause is unlikely to be gallstones) (Fig 17.3).

Figure 17.3 Enlarged palpable gallbladder in a patient with carcinoma of the head of the pancreas.

New onset diabetes mellitus, migratory thrombophlebitis (Trousseau’s sign), venous thrombosis and acute pancreatitis are uncommon presentations of carcinoma of the pancreas. Upper gastrointestinal haemorrhage can rarely result from direct invasion of stomach or duodenum, or from varices due to compression of the portal venous system or involvement of the splenic vein.

Diagnosis

The diagnosis is initially suggested by demonstrating a mass in the pancreas or by dilated bile ducts. On ultrasound scan, this is characteristically hypoechoic. On CT scan, the mass is usually of reduced density compared with the rest of the pancreas. If the tumour is in the head of the pancreas, it commonly produces dilatation of the common bile duct and the main pancreatic duct (the double-duct sign). Lymphatic metastases may be apparent as masses in the porta hepatis. Liver metastases may also be apparent.

Helical CT combined with intravenous contrast (CT angiograph) helps evaluate for resectability.

Endoscopic ultrasound (EUS) is useful to make a tissue diagnosis of a small tumour and to assess resectability. While tissue diagnosis can be achieved by CT or ultrasound-guided needle biopsy it has the disadvantage that the tumour might seed the needle track and this track will not be excised by subsequent surgery. This is not the case for an EUS-guided biopsy. If the tumour is obviously unresectable (e.g. obvious vascular involvement of a portal vessel or superior mesenteric artery or vein, or metastases), the issue of seeding the track is irrelevant. Magnetic resonance cholangiopancreatography will define the pancreatic duct anatomy non-invasively. Look for a long extrinsic compression of the common bile duct; the pancreatic duct may also be compressed.

An endoscopic retrograde cholangiopan-creatography (ERCP) can be done to stent biliary obstruction if surgery is to be avoided. A tissue diagnosis at ERCP is possible for ampullary carcinoma by biopsy and for cholangiocarcinoma by brush cytology.

Histological diagnosis is mandatory for confirmation of the tumour and to rule out focal pancreatitis, autoimmune pancreatitis or other neoplasms, such as lymphoma, islet cell tumours and cystadenocarcinoma, where the prognosis and therapeutic options are significantly different (Ch 26).

The cancer-associated antigen (CA-19-9) is often elevated in advanced disease.

Occasionally, a small (under 2 cm) tumour is demonstrated without evidence of lymphatic or liver metastases in a patient who is young and fit enough to be considered for a major pancreatic resection. Further evaluation is warranted to show that the tumour is resectable and that there are no metastases that have failed to be demonstrated by CT and ultrasound scan. A contrast-enhanced helical CT scan with thin cuts may detect small liver metastases, or encasement of the gastroduodenal artery or superior mesenteric vein or portal vein, demonstrating that the tumour is not resectable. Laparoscopy may demonstrate small peritoneal or liver metastases.

If the mass appears resectable after all imaging, many surgeons will operate without a preoperative tissue diagnosis.

Treatment

Curative surgical resection (e.g. pancreaticoduo-denectomy, i.e. a ‘Whipple’ resection) is the only effective treatment for the disease. Operative mortality in experienced hands is low (2–5%). Unfortunately, fewer than 15–20% of all tumours are resectable at the time of diagnosis. The 5-year survival rate after curative operation is below 30% for node-negative and 10% for node-positive patients. Even in patients who eventually have tumour recurrence, the survival is prolonged three- to fourfold (to a median of 17–20 months) compared with patients not undergoing resection. Untreated non-metastatic pancreatic cancer has a median survival of about 8–12 months (and 3–6 months if there are metastases). Adjuvant chemotherapy alone after resection may improve survival.

The main aim of palliative therapy should be relief of jaundice. This can usually be achieved by endoscopic insertion of a biliary stent. This is attractive because it avoids an operation. If the patient seems likely to survive for more than 6 months, an expanding metal stent (internal diameter 10 mm) can be used rather than conventional 3-mm plastic stent, which tends to block with sludge and needs changing every 3 months. Surgical biliary bypass (choledochojejunostomy) is rarely performed these days except in patients operated on with curative intent who are found at operation to be unresectable. In that circumstance a gastroenterostomy can be performed at the same time. Otherwise the 10% of patients who develop gastric outlet obstruction will usually be palliated with an expanding metal uncovered duodenal stent. Chemotherapy and radiotherapy have not been shown to be very effective, increasing median survival by only a few months in locally advanced cancer.

In those with hereditary chronic pancreatitis, screening for pancreatic cancer is recommended from age 35 years. Similarly, those with a family history of pancreatic cancer can be offered screening 10 years before the age at which the cancer was diagnosed. Spiral CT or EUS are recommended in these cases, but the tests are not very sensitive in this setting.

Cystic lesions of the pancreas found by cross-sectional imaging that have a high potential for malignancy include the following:

Clinical features

Weight loss and progressive dysphagia for solids are the initial symptoms in most patients. Dysphagia progresses later on to include semisolids and liquids. Progressive dysphagia is, therefore, always an alarm symptom and mandates appropriate investigation, usually upper endoscopy (see Ch 2). Unfortunately, however, diagnosis at this stage often indicates incurable disease.

Diagnosis

Endoscopy helps to delineate the nature and the extent of the lesion, and biopsies will usually confirm the diagnosis. The tumour spreads initially through the wall of the oesophagus and then via lymphatics to adjacent lymph nodes. Once the diagnosis is confirmed histologically, tumour extent is ascertained by a CT scan of the chest and upper abdomen and subsequently by positron emission tomography (PET) scanning. PET whole-body scanning is more sensitive for distant metastases than CT, detecting bony as well as liver and lung metastases and also metastases in totally unexpected positions. EUS is being used increasingly for additional regional staging. Thus, it is possible to assess how far through the oesophageal wall the tumour has penetrated and whether enlarged local perioesophageal lymph nodes have been infiltrated by the tumour. Nodal involvement is more reliably ascertained by fine needle aspiration biopsy of one or more of those nodes.

Treatment

Apart from early oesophageal cancers (e.g. those detected during Barrett’s screening [see Ch 1] that are treated by curative surgery), the prognosis is generally poor (the 5-year survival rate is about 5% for all patients, but as high as 20% for patients selected for surgical resection). Nevertheless, surgery offers the only hope of cure and, as long as the tumour can be resected with clear margins, this achieves the best palliation. Preoperative chemoradiotherapy has been shown to improve the disease-free interval and possibly survival. Unfortunately, many patients are too old or frail to tolerate this approach. In those unsuitable for surgery by a specialist oesophageal surgeon, palliation of dysphagia can be achieved by placement of an expandable metal stent. Palliative chemotherapy and radiotherapy have limited roles.

Pathology

Adenocarcinoma accounts for the majority (over 90%) of gastric carcinomas (Fig 17.4). Lymphomas account for most of the remainder. Adenocarcinomas can be further classified histologically into intestinal and diffuse types. The intestinal type is characterised by cohesive neoplastic cells, which form gland-like structures and are frequently polypoid. The diffuse cancers lack cohesion, are usually ulcerative and develop throughout the stomach. Adenocarcinomas are also staged into early and advanced cancers. In early cancers, the depth of invasion is limited to the submucosa; if detected early, gastric cancer is potentially curable with resection.

Figure 17.4 Gastric adenocarcinoma of the stomach.

Aetiology

Chronic atrophic gastritis, which begins as a multifocal process, can progress in those predisposed to intestinal metaplasia and dysplasia. This sequence can ultimately lead to cancer. H. pylori is classified as a class I carcinogen by the World Health Organization; it causes chronic atrophic gastritis and is linked to gastric adenocarcinoma, mucosa-associated lymphoid tissue (MALT) lymphoma and B-cell lymphoma. Patients with H. pylori infection have a higher risk (three- to sixfold) of developing non-cardia gastric adenocarcinoma. Other risk factors for gastric cancer are listed in Box 17.6. Changes in multiple oncogenes and tumour suppressor genes (e.g. MCC, APC and DDC) have been identified in gastric cancer.

Clinical features

Gastric cancer in its early stages is asymptomatic and is diagnosed either incidentally or through a screening program. With symptomatic presentation, advanced disease is often already present. The key symptoms are upper abdominal pain and weight loss. Anorexia and nausea also occur in about one-third of patients. Lesions around the cardia can present with dysphagia as the predominant symptom.

Typically gastric carcinomas spread to local lymph nodes and/or the liver.

Diagnosis

Gastroscopy with biopsy is the standard method for diagnosing gastric cancer. To increase the accuracy, multiple biopsies (more than 5) are recommended. All gastric ulcers should be biopsied to rule out the presence of neoplasm.

The tumour is staged prior to surgery first by CT scanning looking for lymph node metastases, liver metastases and ascites, then by laparoscopy to detect smaller liver and peritoneal metastases. PET is also used as an adjunct, as it is in assessment of oesophageal tumours.

Treatment

Complete surgical resection of the tumour (and adjacent lymph nodes) is the only chance for a cure. In distally located tumours, the distal stomach is removed. For proximally located tumours, the whole stomach and sometimes the distal oesophagus are removed. Adjuvant chemoradiotherapy has recently been shown to be beneficial.

Surgery may also afford a means of palliation in patients with gastric outlet obstruction or significant gastrointestinal bleeding. Combination chemotherapy can be used to palliate some non-surgical candidates with advanced gastric cancers. However, the medial survival with combination chemotherapy is only 6–10 months, and is toxic.

Prognosis

The most important determinant of prognosis is stage. In early gastric cancer, the incidence of lymph node involvement is about 10%, and the 5-year survival is about 75%. On the other hand, advanced gastric cancer (with serosal involvement) will have spread to lymph nodes in about 70% of cases and has a dismal 5-year survival rate of 5%.

Gastric carcinoid

These are rare. They grow slowly, rarely metastasize, and rarely cause the carcinoid syndrome. The aetiopathogenesis is related to any chronic high gastrin state. Carcinoids are classified as follows: type 1 is found in association with pernicious anaemia (autoimmune gastritis); type 2 in Zollinger-Ellison syndrome (gastrinoma); and type 3 is spontaneous (associated with vitiligo). Proton pump inhibitors have not been found to be a cause.

Gastrointestinal stromal tumours

Gastrointestinal stromal tumours (GIST) are rare mesenchymal tumours that may cause mass effects, or lead to bleeding, pain or obstruction. They can occur anywhere in the gastrointestinal tract, but the stomach is most often involved; they most often metastasise to the liver. ‘Carney’s triad’ comprises a gastric GIST with a paraganglioma, and a pulmonary chondroma, usually in young women.

At upper endoscopy, a submucosal mass bulging into the gastric lumen with smooth margins and normal overlying mucosa is typically seen; EUS and fine needle aspiration or biopsy are often needed to make the diagnosis. All GISTs 2 cm in size or larger should be resected if possible. Approximately 80% of GISTs have mutations in the KIT proto-oncogene; tyrosine kinase inhibitors such as imatinib halt tumour proliferation, and this is used as adjuvant therapy for lesions at high risk of metastatic disease.

Clinical features

Young females in the pubertal age group are at the greatest risk. Amenorrhoea is usually present. A history of food fads, food avoidance, excessive use of purgatives or diuretics and self-induced vomiting is common. Mental irritability, depression or agitation can co-exist. The menstrual cycle is absent for three or more cycles. These patients typically manifest an extreme loss of fat and muscle bulk, leading to gaunt faces, atrophic breasts and loss of body contour. Hypotension, hypothermia and bradycardia may also be evident. Lanugo (soft, down-like hair), dry skin and brittle nails are common.

Pathogenesis

Distorted body image is a central abnormality; even extremely thin and emaciated patients consider themselves to be overweight, inducing them to self-starvation. There exists an association between anorexia and major depressive illnesses, as well as obsessive-compulsive behaviour, personality disorders and substance abuse. There is a tendency for these patients to be high achievers and perfectionists.

Complications

The medical complications arise from starvation. Hypokalaemia, hypochloraemia and metabolic alkalosis are typical (Table 17.4). Cardiac complications are the most frequent cause of death in these patients. Prolongation of the Q-T interval is thought to predict the onset of serious cardiac arrhythmias. As glucose metabolism and insulin secretion are disturbed, hypoglycaemia is common and potentially lethal. Osteopenia from oestrogen deficiency is common and can lead to debilitating fractures.

Table 17.4 Laboratory findings that may occur in patients with anorexia nervosa

Treatment

A multidisciplinary approach is required. Outpatient therapy is increasingly employed. Intense cognitive therapy and psychotherapy are the mainstays of treatment. Oral feeding is usually commenced in small amounts but occasionally parenteral nutrition may be needed in dire circumstances. Patients may resort to vomiting, purging, or surreptitious disposal of food or medications. Hospitalisation and a supervised feeding program are needed in patients with moderate to severe disease (where the body weight is below 75% of ideal weight). Such patients mostly require prolonged hospital admission (average: 60–90 days) to achieve full nutritional rehabilitation. Malnourished patients are less responsive to tricyclic antidepressants and more likely to develop side effects, especially arrhythmias and hypotension; they should be used only when depression is not improving despite weight gain. Selective serotonin reuptake inhibitors are useful for reducing relapse. Cyproheptadine, an appetite stimulant, is of little benefit. Antipsychotics may have a role in some patients.

Approximately 20% of patients have a relapse and 10–20% die as a result of ventricular arrhythmias, opportunistic infections, suicide or starvation. An equal number remain chronically ill. Prognosis is worst in those with later onset of disease.

Clinical features

Bulimic patients have a tendency to hide their illness. Body weight is usually near normal and only about 50% of patients have amenorrhoea. The following signs may sometimes be present:

Hypokalaemia and metabolic alkalosis (from vomiting or laxatives) may be present.

Treatment

As with anorexia nervosa, a similar multidisciplinary approach is necessary. Pharmacotherapy has a greater role to play and often higher doses of medications are required. Fluoxetine (up to 60 mg/day) has been best studied, but only one-third of patients go into remission. A combination of an antidepressant plus cognitive behavioural therapy appears to be better (up to 50% remission). Individuals who have milder symptoms at the commencement of treatment tend to have a better prognosis than those individuals who are disabled and functioning poorly at the start of treatment. Additionally, other indicators of poor prognosis include premorbid personality disturbance, low self-esteem, impulsiveness and persistent body image dissatisfaction.