SKIN CANCERS
Cancer of the skin most commonly affects people of fair-skinned northern European descent in regions closer to the equator, such as Australia. Australians have the world’s highest incidence of skin cancer, followed by the white populations of the southern regions of the USA.
There are three basic types of skin cancer: basal-cell carcinoma (BCC), which is by far the most common and, fortunately, the least dangerous; squamous-cell carcinoma (SCC), which is the next most frequent; and melanoma, which is much rarer but the most dangerous.
BCC
A BCC is usually first noticed as a small crusty patch, nodule or ulcer. These cancers occur most commonly in skin that has been constantly exposed to sunshine over many years. Hence they are not common before the age of 40 and become more frequent with increasing age. More than 70% of these cancers occur on the face, as it is most constantly exposed to the sun. The next most common sites are the neck, the backs of the hands or forearms, the lower legs, chest and back.
BCCs are not painful and are usually slow growing; patients may have noticed them for months or even years before they seek medical attention. If neglected, they usually develop as slowly enlarging ulcers (sometimes called ‘rodent’ ulcers because they may look like skin that has been gnawed by a rodent). Although, fortunately, they almost never spread to lymph nodes or other distant tissues, they do tend to erode locally into tissues around them. If neglected for a long time, they may become incurable or even fatal by causing destruction to such tissues as underlying cartilage of the nose or ear, the underlying bone of the skull or large blood vessels in the neck. They can sometimes invade the orbit and paranasal sinuses and may even erode into the brain.
Treatment
BCCs can be easily and effectively cured in their early stages by simple surgical excision, usually under local anaesthesia. The specimen of tissue excised is examined under a microscope by a pathologist to confirm that it was a BCC and that it was completely excised with an adequate margin of normal tissue. Radiotherapy is also an effective method of treating many BCCs but preferably after a small biopsy has been taken to confirm the diagnosis. Radiotherapy has the advantage of avoiding surgical operation and being a painless procedure; it has the disadvantage of requiring expensive specialised equipment and personnel and several treatment attendances, and it leaves some permanent damage to a small patch of skin. Another disadvantage is that if no tissue is removed, there may be some doubt about the exact diagnosis of the lesion and whether it was completely eradicated. However, for many small lesions, especially in elderly patients, it may be the most appropriate form of treatment.
Sometimes small BCCs are removed by dermatologists (skin specialists) using cauterisation or a small curette (a scraping instrument). These techniques should be left to experienced experts, as a mistake in diagnosis or incomplete removal can lead to a greater problem.
BCCs that recur after previous failed attempts at treatment, or those occurring close to vital structures such as a tear duct or an eyelid, present special problems and require expert attention.
Large BCCs invading bone or other tissues may require extensive surgical procedures, including reconstructive surgery. Occasionally they may even be incurable and are possibly best treated by palliative radiotherapy. (Palliative treatment will give a patient relief by reducing the cancer or lessening its symptoms, without being likely to cure it.)
Although such advanced lesions are rare, they are disastrous when they do occur and can easily be prevented by correct treatment in their early stages. Hence the importance of people with small lesions seeking medical help early when BCCs are easily and completely curable.
SCC
SCCs are also most common on the skin of the face, especially the lower part of the face and lower lip, but they also often occur on the neck, the backs of the hands or forearms and the skin of other frequently exposed areas such as the legs, back or chest. People who have had kidney transplants are at high risk for frequent and recurrent SCCs because of the immunosuppressive treatment they receive.
SCCs often develop in skin lesions called hyperkeratoses, which are small, crusty or flaky thickened areas of skin resulting from previous longstanding sun damage.
An SCC is usually first noticed as a small, painless lump growing on the skin’s surface or as an ulcer in the skin. SCCs usually grow more rapidly than BCCs and after a time tend to spread to nearby draining lymph nodes. Later, they may spread further to more distant lymph nodes or even to other distant tissues or organs such as the lung. They also grow locally and are likely to invade surrounding tissues that may ulcerate, bleed and become painful.
Fortunately, most SCCs of the skin have not spread when they are first diagnosed, and treatment of the draining lymph nodes is usually not required. However, the draining lymph nodes must be kept under close observation and in case of enlargement should be treated without delay, usually by surgical excision.
Treatment
As for all cancers, the earlier these lesions are diagnosed and treated, the less radical the treatment they need and the greater the likelihood of cure.
For any lesion suspected of being an SCC, it is important to obtain a tissue diagnosis; that is, for a biopsy to be taken. In the case of a small lesion, this may be best achieved by surgical excision of the whole lesion (an excision biopsy). For a large lesion it is usually more appropriate for a small piece of tissue to be taken from its edge for biopsy and microscopic examination (an incision biopsy). A frozen-section examination of a biopsy specimen, as described in Section 2, may be appropriate to allow complete treatment to be carried out without delay.
Once the diagnosis of an SCC is established, treatment is by surgical excision or sometimes by radiotherapy. Surgical excision is usually the most effective and most appropriate treatment. The lesion is widely excised and examined microscopically to confirm that a margin of normal tissue surrounding the cancer has also been excised, ensuring that removal of all the primary cancer has been achieved. If the draining lymph nodes are enlarged, without evidence that this is due to infection, the lymph nodes should also be removed, in one block of tissue. Depending on the site and how much tissue has to be excised, a plastic surgical procedure such as a skin graft may be needed to repair the tissue and close the wound.
As in the case of BCCs, radiotherapy may be used to treat some SCCs of the skin, especially in elderly patients, in cases where an operation might be risky or occasionally as palliative treatment when cure by surgery is not possible.
Occasionally when an SCC of skin is very advanced or invading vital organs or other tissues, or when it has become incurable by local surgery because of secondary spread, it may be appropriate to use anti-cancer drugs to reduce the extent and size of the cancer and to relieve symptoms. Large SCCs of the skin sometimes appear incurable by radiotherapy or surgery (or only curable by mutilating surgery such as amputation of a limb). These can occasionally be reduced in size and extent by chemotherapy first, especially when given regionally by intra-arterial infusion (as described in Section 2). After chemotherapy the cancers are often so reduced in size, extent and viability that they can be cured by radiotherapy and/or local surgical excision.
Melanoma
Melanoma, the most dangerous form of skin cancer, is a malignant growth of pigment-forming cells in skin or the eye. Occasionally they may occur in mucous membranes such as the lining of the mouth or anus.
Although melanoma is a highly malignant tumour, present-day management methods have greatly improved the outlook. Considered to be incurable in about 50% of patients 50 years ago, melanoma in Australia, where it is usually diagnosed early, is now cured in more than 90% of cases.
The exact cause of melanoma is not known, although it is most common in fair-skinned people living in sunny tropical or subtropical climates. Unlike BCCs and SCCs, however, melanoma is not more common on the areas of the body most constantly exposed to sunshine. The most common sites are on the backs of men and the thighs of women. However, in common with other skin cancers, the world’s highest incidence of melanoma is in the white population of Australia, especially those living closest to the equator and nearest to the seaside. The white population of the sunny southern parts of the USA also has a high incidence of melanoma. People of dark-skinned races do occasionally develop a melanoma, but in these people it is more commonly at sites of less pigmentation, such as the sole of the foot, under fingernails or toenails or in the mucosal lining of the mouth or anus.
Melanoma rarely affects children before puberty. After puberty it can affect people of any age, including teenagers and young adults as well as middle-aged and older people. Melanoma is now more common in men, and the survival rate for women is better.
The danger of melanoma lies in the fact that it can spread relatively early to draining lymph nodes and to distant organs such as the liver, lungs, bowel wall and brain. The outlook has improved because people in general, and doctors in particular, are more aware of the early features of melanoma and the need to commence treatment as early as possible. Most melanomas develop in pre-existing moles in the skin, but others develop in areas of unaffected skin. Occasionally a melanoma will develop without pigment. This is known as an amelanotic melanoma and can be diagnosed only by microscopic examination. Amelanotic melanomas behave in a similar way to pigmented melanomas and require similar treatment.
Symptoms and signs
Any evidence of increasing pigmentation in a spot in the skin, or an increase in size or pigmentation of a mole, must be regarded with suspicion. Other early features may be itching or crusting of a mole. Bleeding and ulceration are usually later features. Any of these features occurring either in a pre-existing mole or in a newly pigmented spot require immediate attention, and if there is any doubt an excision biopsy should be done.
Treatment
Surgical excision of early lesions offers the best hope of cure. Early melanomas can be excised with generally a 1 cm margin of normal surrounding tissue as their cells are sometimes present in tissues or even in lymphatic vessels surrounding the cancer. Thicker, crusted or bleeding melanomas require a wider margin. If there is evidence of draining-lymph-node involvement, then these lymph nodes should also be excised in one block of tissue. The likelihood of the melanoma spreading is directly related to the thickness (depth) of the malignant cells, so that in the case of thick lesions, a sentinel-lymph-node biopsy may be performed. This is similar to the procedure performed in breast cancer. A dye or radio-tracer is injected into the skin near the melanoma. This allows discovery and removal of the first draining ‘sentinel’ node or nodes. This node (or sometimes two or three nodes) is then examined microscopically by the pathologist. If it is involved with metastatic disease, the remaining nodes in that group are also surgically removed.
Melanomas are not particularly sensitive to radiotherapy, although radiotherapy may be helpful in some situations such as for a secondary melanoma in the brain. They are also generally resistant to chemotherapy.
When advanced melanoma appears to be confined to one limb, treatment by more concentrated regional chemotherapy, via a special technique into the blood supply of that limb only, often achieves worthwhile improvement, with cancer regression. This technique is called ‘closed circuit’ or isolation perfusion. A newer, more easily used technique is ‘closed circuit infusion’. This treatment is more effective if heat is used with the chemotherapy and appears to be even more effective if the new immunotherapy agent TNF (tumour necrosis factor) is used with chemotherapy.
Immunotherapy is also sometimes used in the treatment of advanced or widespread melanoma. Although some improvements have been observed with general (systemic) immunotherapy, most results have been inconsistent, and early hopes of a reliable new cure have not yet been fulfilled. In some patients with lymph-node involvement, a high dose of interferon is given to try to prevent recurrence, but side effects may make this quite difficult for the patient to cope with.
Trials with chemotherapy and immunotherapy are ongoing in melanoma clinics in the hope of improving outcomes for patients with more advanced stages of disease.
LUNG CANCER
Cancer of the lung, a relatively rare disease prior to World War I, now causes more deaths in males than any other cancer. It will soon overtake breast cancer as the main cause of cancer death in women. These rapid increases in incidence are directly related to cigarette smoking. The disease is ten to 20 times more common in smokers than in non-smokers.
Although tobacco smoking is by far the most significant cause, a number of other factors may also play a part in some cases, including industrial and automobile pollutant gases. Workers in certain industries, including the chromium, arsenic and asbestos industries, may have an additional increased incidence, especially if they are smokers.
Symptoms and signs
In its early stages lung cancer usually causes no noticeable new symptoms, so it is often diagnosed at an advanced stage when it is incurable. This may be due to lack of recognition of an increasing cough in heavy smokers who have had a cough for years. Other than a cough the common symptoms are bloodstained sputum, chest pain and episodes of chest infection or pneumonia, which do not completely resolve after treatment with antibiotics.
The first signs of lung cancer may also be evidence of metastatic spread to lymph nodes, bone, brain or elsewhere. In rare cases lung cancers produce hormone-like substances that may result in changes to other parts of the body such as swelling of the breasts, changes in bones, fingernails (clubbing) or loss of various brain or nerve functions.
Investigations
By the time symptoms are present, a chest X-ray will almost always reveal the cancer, but chest X-rays done for some other reason will sometimes show a lung cancer that has not been causing symptoms.
CT scans will show more clearly the position and size of a lung cancer in relation to other structures.
Bronchoscopy (examination of the air passages with a bronchoscope) will often allow the doctor to see a tumour in the larger airways (bronchi). A biopsy of the suspected cancer may be taken and examined under a microscope to confirm that cancer is present, to find out what sort of lung cancer it is and therefore how best to treat it.
Sometimes a cancer cannot be seen through a bronchoscope but can be detected in sputum that has been aspirated (sucked out) or coughed up and examined under a microscope. This test is called cytology. It will often show cancer cells if a cancer is present. If a lump is seen on X-ray, sometimes it is possible to aspirate cells for cytology from the lump through a needle inserted through the chest wall (see Section 2).
Treatment
A major advance has been the application of PET scanning (see Section 2). This has improved the ability of doctors to determine whether a lung cancer is operable or not. As well as the actual primary cancer any cancer extension or metastases will take up the radio-isotope labelled tracer. In many patients this test will avoid a futile operation where the chest is surgically opened and an unremovable cancer discovered. However, for those patients with localised disease, surgical resection offers the best chance of cure. PET scanning can also better define the exact extent of inoperable cancers to allow intensive local radiotherapy to begin without delay in some patients. A number of these patients can experience long-term remission with this approach. In some patients it is necessary to follow up lung-resection surgery with a combination of chemotherapy and radiotherapy: adjuvant therapy. Palliative chemotherapy for inoperable or metastatic lung cancer has improved with the new types of drugs that have become available in the last few years. Remissions, with improved quality of life, may last for several months.
Mesothelioma
Mesothelioma is a rare form of cancer occurring usually in people who have been exposed to asbestos either at work (e.g. in the construction and insulation industry or in the manufacture of asbestos products) or in home renovations. Mesothelioma is a malignancy of the tissues surrounding and lining the lungs (the pleura). It may also commence in the lining of the abdominal cavity (the peritoneum).
Symptoms
Mesothelioma patients may seek treatment for a cough, chest infection, difficulty with breathing or chest pain and a general feeling of being unwell and without energy.
Signs
Patients first consulting with mesothelioma often look pale, thin and with decreased movement of the chest and distressed breathing. They may be found to have a cancer or fluid collection around the lungs. The fluid collection may be seen on an X-ray or CT scan.
Mesothelioma is almost always fatal, as it is usually too widespread to treat by surgery. However, in some patients with relatively limited disease surgical removal of any obvious cancer mass may improve survival. The accumulations of fluid in the chest cavity can often be controlled by a pleurodesis, that is a procedure that causes the lung lining to adhere to the chest wall lining by injection of a special form of talc powder into the chest cavity. This procedure obliterates the pleural cavity around the lung so that fluid can’t collect there and press on the lungs. Newer forms of chemotherapy can also achieve remissions lasting several months. Obviously, expert palliative care is critical to reduce symptoms to a minimum.
Secondary (metastatic) cancer involving the lung
Other than the nearby lymph nodes, the lungs (together with the liver) are the commonest sites of metastatic cancer. Cancers from almost any primary site can spread through the bloodstream to the lungs, e.g. from cancers of the breast, bowel, lung, kidney, testis, bone and melanoma of skin. Shortness of breath (dyspnoea) or cough are the main symptoms. Secondary cancers in the lungs usually show as a number of rounded opacities (white spots) on chest X-rays, although sometimes a secondary (especially from the kidney) may be single, showing as just one round white spot on an X-ray. Treatment depends on the type of primary cancer that has spread to the lung. Patients may respond to the specific forms of chemotherapy known to be effective for the primary-site cancer. For most cancer types this treatment will only be palliative, but sometimes, for some cancers, a cure is possible, especially with testicular cancer or lymphoma. For some patients with a limited number of metastases, surgical removal may be appropriate, and this may be curative (e.g. occasionally with melanoma, renal, testicular and bowel cancer, and bone and soft-tissue sarcomas). In metastatic breast or prostate cancer good remissions are sometimes possible with hormonal treatments (see Section 2).
Commonly, primary or secondary cancer in the lung will cause fluid to collect around the lung in the pleural cavity. This is known as a pleural effusion. This fluid can accumulate to the extent of several litres, causing shortness of breath as a result of pressure on the lung. Patients will get good relief following removal of this fluid with a simple drain tube or aspirating needle. This is often done in the X-ray department with ultrasound guidance. Talc-powder pleurodesis is commonly done in patients with recurrent effusions (see ‘Mesothelioma’ earlier).
BREAST CANCER
Breast cancer is now the most common cancer affecting women in Europe, the USA and Australia (excluding skin cancers). About one in ten Australian women will develop breast cancer during their lifetime. Although it is occasionally seen in younger women, breast cancer is not common until after the age of 40. The incidence then increases with age. The average age for women first presenting with breast cancer is about 60 years.
Although a specific cause of breast cancer is not known, there are a number of contributory factors. A highly significant factor is the age of a woman when she has her first child. Having a baby at an early age seems to give some protection, as breast cancer is least common in women who had their first babies as teenagers. It is more common in women who did not have their first baby until after the age of 30 or 35 years. This social phenomenon is one of the explanations for the increasing incidence of breast cancer in recent years. Women who have not had children are at greater risk from breast cancer.
The age at onset of menstruation and the age at menopause are also significant. Early menstruation and late menopause are both associated with an increased risk of breast cancer. Again these are related to improved modern Western standards of living. It seems that the greater number of years the woman’s reproductive function continues, reflecting continuous exposure to the female sex hormone oestrogen, the greater the risk of breast cancer.
There may also be some protection in breastfeeding, although the evidence for this is less clear. This may be a result of reduction in oestrogen synthesis at this time.
There is an association between breast cancer and Western lifestyle factors such as a diet high in animal fat, obesity and alcohol, although these associations are not as clear as they are for tobacco smoking and lung cancer.
Breast injury is not known to cause breast cancer. Although some women first notice a lump after an injury that is in fact breast cancer, it is likely that in most cases the injury simply drew attention to the cancer that was already present. Injuries may, of course, cause other types of lumps in the breast that are not cancer.
Hormone-replacement therapy (HRT) has been suspected of increasing the risk of breast cancer. However, unless the woman had previously been treated for breast cancer or has some special risk factor (such as a strong family history of breast cancer), the risk of the small doses of hormones in HRT is small.
Nevertheless, for this reason, HRT is not given to every woman who reaches the menopause. For those with severe menopausal symptoms the improvement in quality of life may justify the small increased risk, provided the woman is kept under regular observation. Meanwhile, studies continue to try to find other forms of risk-free therapy to relieve these symptoms. One study is investigating the use of phytoestrogens that occur naturally in soybeans and other plant foods.
Cancer in the male breast does occur but at a rate of about 1% of that occurring in women. Such cancers behave in a similar way to cancer in female breasts. The approach to treatment is similar to that in women, with a similar outcome. A problem, however, is often a delay in diagnosis.
Symptoms and signs
Breast cancer is usually first noticed when a woman finds a painless lump in the breast. The most common location is in the upper outer part of the breast, and the lump is often first felt in the bath or shower when fingers are soapy and lumps are more easily felt.
By far the majority of breast lumps are not cancer. However, when a woman first notices a lump in a breast, she should have it examined by a doctor. If necessary, the woman should be sent for further investigation or for a specialist opinion.
Other features of breast cancer may be a change in the position or shape of a nipple (called retraction or inversion); puckering or ulceration of skin over the breast, especially if over a lump; discharge of blood from a nipple or discharge of other fluid from a nipple not associated with a pregnancy or lactation; redness of a nipple; or a change in the size of one breast. Occasionally the first indication of breast cancer is a red inflamed breast resembling breast infection (acute mastitis). If an acute mastitis develops for no apparent reason or does not settle down with appropriate treatment (including antibiotics), the possibility of an underlying cancer must be considered.
Sometimes breast cancer may first be discovered after finding a lump in the armpit (axilla) or a cancer lump (secondary) in another organ such as in lungs (seen in a chest X-ray) or the liver or bone.
Investigations
Screening tests for breast cancer were discussed in Section 2. In an examination for possible breast cancer the doctor will first look for a breast lump. The doctor will take note of the relative hardness of any lump and an irregular outline or attachment to the skin, muscle or other tissue. The doctor will examine lymph nodes in the axilla (armpit) or elsewhere for evidence of enlargement and may also examine the chest and abdomen for possible evidence of lumps or spread into other organs such as the lungs, liver, bone, ovaries, etc.
A number of investigations are available for detecting breast cancer. Breast X-rays (mammograms) may show the type of lump and the general condition of the breast. Ultrasound and CT scans may also be helpful, although as a rule they give little further information.
The most important investigation is a biopsy. In many cases a needle biopsy may be carried out on an outpatient basis. Sometimes it is better for a surgeon to take a larger biopsy in an operating theatre: this is the most reliable method of diagnosis. If a surgical biopsy is carried out with the frozen-section pathology technique (described in Section 2), the surgeon may be able to go ahead with any necessary surgical operation without further delay.
If, after a doctor’s examination, a breast lump is thought to be cancer, and especially if it is an advanced cancer, other general investigations will be arranged. These may include chest X-rays, liver ultrasound scans, bone scans or CT scans, which may provide evidence of possible spread to lungs, liver or bone. The involvement of any of these organs should be known before any major surgery is carried out on the breast. If other organs are affected, some form of treatment other than breast surgery may be more appropriate.
Treatment
Treatment of breast cancer will depend on whether the cancer was detected early and is likely to be cured by surgery or other local treatment, or whether it is so advanced that cure by surgical treatment of the breast alone is not possible.
Prevention
There is no simple specific way of preventing development of breast cancer apart from possibly a change in Western diets and the lifestyles of girls and young women in high-risk communities. However, studies are being conducted on the use of the anti-oestrogen hormone compound tamoxifen, given over a period of up to five years (or even longer in special circumstances), to prevent breast cancer developing in women who are at special risk. These include those with a high incidence of breast cancer in their immediate family or those who have already had cancer in one breast. The results of these trials, especially in deciding who would most likely benefit, are at this time inconclusive. Whether there would be any advantage in using the newer anti-oestrogens Femara or Armidex has yet to be fully tested.
Women in Asian countries have a lower incidence of breast cancer and premenstrual syndrome than women in Western societies. Asian women have a diet high in soybeans and other foods that contain the natural plant hormone substances known as phytoestrogens. There are ongoing studies designed to determine whether the phytoestrogens from these dietary products reduce the risk of breast diseases, including cancer.
A major advance has been the recognition that in certain families specific gene mutations predispose to breast cancer. There are now special DNA or gene tests for these mutations to determine individuals at risk. Such women may then have intensive surveillance.
Early breast cancer
Surgery and/or radiotherapy
The treatment of early breast cancer has, for many years, been an emotive topic.
Previously, surgeons considered that the best chance of curing breast cancer was the total removal of the breast and all of the draining lymph nodes in the armpit. This operation, known as a radical mastectomy, was performed for many years and cured many women of breast cancer. However, it was greatly feared because of the mutilation involved, as well as the risk of lymphoedoma (arm swelling). Over the last 20 years large clinical trials in the USA, Europe and Australia involving thousands of women have, thankfully, dramatically improved the situation. Firstly these randomised clinical studies have shown that, in women with relatively small tumours, it is possible to simply remove that part of the breast containing the cancer. This is called a segmental or partial mastectomy or sometimes a ‘lumpectomy’. It is usually followed by radiotherapy to the affected breast in case any cancer cells have escaped the surgery and remain somewhere in the breast. Similarly trials, still underway, suggest it is only necessary to remove the so-called sentinel lymph node (or sometimes two or three nodes) in the armpit. This can be identified by injecting a coloured dye into the skin of the breast near the cancer. Alternatively a radio-isotope tracer may be used. This is similar to the procedure used in surgery for melanoma. Removed nodes are then examined by the pathologist for cancer cells. The results of this are critical in determining the patient’s outlook. Generally if a sentinel lymph node is involved then some form of additional therapy is given (see below). The removal of only one or two nodes from the armpit reduces the risk of lymphoedoma developing in the arm. (There are up to about 30 nodes in total in each armpit, but the sentinel node or nodes are most likely to be first to be involved with any cancer spread.)
It is important that the patient receive a careful explanation of the various treatment alternatives available. Obviously the patient’s wishes should be taken into consideration. If the patient would prefer to have the breast with a cancer in it totally removed, then this treatment can be offered. On the other hand, where a patient has a wish for less radical surgery with breast conservation this is now usually very appropriate. Results are essentially the same.
Adjuvant chemotherapy
It has long been recognised that many women, particularly those with lymph-node involvement, have an undetectable spread of some cancer cells to other parts of the body, such as the lungs, liver, bones or elsewhere (micrometastases). These are the cause of subsequent relapse or recurrence of the disease months or years after apparently successful surgery. If chemotherapy or hormonal therapy is given soon after surgery, these small but undetected clumps of scattered cancer cells, if present, are more likely to be destroyed than if they are allowed to grow and actually cause symptoms or signs. In women who have had an early breast cancer removed that involved lymph nodes in the axilla, a program of chemotherapy and/or hormone therapy is usually given after the surgery. This is known as adjuvant therapy, the chemotherapy being an adjunct or assistant to the surgery. Women given adjuvant therapy are less likely to develop secondary cancer and are therefore more likely to be cured. As indicated in Section 2, the chemotherapy must be given skilfully and the effects watched closely, as side effects are common. The specific types of therapy will depend on a number of factors including the woman’s age, the size of the primary cancer and whether hormone receptors are present in the cancer specimen. Adjuvant chemotherapy is more appropriate for younger women, who appear to benefit more and also better tolerate the effects of chemotherapy than older women. Hormone therapy is usually more appropriate for older women. For many years tamoxifen, which antagonises oestrogen, had been used. It is now being replaced by the drug Arimidex, which prevents synthesis of oestrogen (see ‘Hormone therapy’ in Section 2).
About 20% of women will have increased amounts of a cancer-cell surface receptor, a protein called HER2. They may be treated with an artificially manufactured antibody called Herceptin. In many treatment centres women will be asked to participate in clinical trials of new treatments being studied. These trials are quite safe and offer patients the chance to receive some of the newer therapies. Patients entering such trials are carefully monitored and are contributing to knowledge that may help other women in the future.
Locally advanced breast cancer
Rarely women may present with a breast cancer that has become locally advanced. Such cancers are large and may ulcerate (fungate) through the skin of the breast or the nipple, or may possibly be fixed to the chest wall. Commonly such women will have enlarged axillary lymph nodes. Unfortunately the outlook for such women is much poorer than those with early or smaller cancers. However, a small percentage can be cured, and many will gain some years of good-quality life.
A small biopsy of the tumour is taken to confirm the diagnosis and is also sent to the pathologist for assessment of its hormone-receptor status (oestrogen-and progestrogen-receptor status) as well as the HER2 receptor. Depending on the age of the women, these patients may be treated with vigorous chemotherapy to shrink the cancer mass. This is often enough to then allow surgery in which usually the cancer and the entire breast is removed. This is then generally followed by radiation therapy to the site of surgery. In some rare cases, if the local cancer is very big or fungating through the skin, the chemotherapy may be more concentrated in the cancer if given directly into an artery, or arteries, supplying the breast with blood. This will give an even greater chance of shrinking the cancer sufficiently to allow its removal by surgery (see Section 2).
Older women, particularly if their cancer is oestrogen-receptor positive, may be simply treated initially with tamoxifen or Arimidex, which will usually lead to slow shrinkage of the cancer lump. This may eventually result in a much smaller tumour that can be surgically removed and followed by radiation therapy to the breast.
Patients so treated may remain well for some years. Often for very elderly patients that is all that is required as they may have other coexisting diseases (e.g. heart or cerebro-vascular disease). For younger women a small percentage may be cured, but often, unfortunately, the disease may either relapse locally or, because of distant spread, metastases may appear.
Metastatic breast cancer
In this situation, possibly many months or years after treatment of the initial primary breast cancer, spread of the disease may become apparent by the appearance of metastases. Bone metastases are one of the more common forms of presentation, and women may present with non-specific symptoms such as backache, or even what is called a pathological fracture of a bone, where trivial trauma leads to a bone fracture. X-rays generally demonstrate changes in the bone where they have become thinned by the presence of the cancer. Various scans are then done to assess the spread of the cancer.
Similarly, metastases in the liver or lung may be discovered. Rarely, but generally in the late stages of the disease, it is possible to develop metastases in the brain. Again, treatment, although not curative, may allow women many months or even several years of good-quality life. The best outcomes occur when the original tumour or metastatic tumour is shown to contain hormone receptors. Treatment may then just consist of hormonal therapy such as the drugs tamoxifen or Arimidex.
Locally troublesome symptoms (e.g. bone pain) can often also be dealt with by radiotherapy. Bone fractures are attended to by the orthopaedic surgeons with pinning and plating as necessary followed by radiation therapy.
Women with cancers that do not contain hormone receptors usually require a course of chemotherapy. Various combinations of the anti-cancer drugs (described in Section 2) may be used, and this may be combined with the monoclonal antibody Herceptin, if the cancer is positive for the HER2 receptor.
It is important that complications are also adequately treated, to relieve symptoms such as those caused by accumulation of fluid in the pleural cavity or abdominal cavity and provide appropriate treatment of pain.
Some years ago very high-dose chemotherapy with bone-marrow transplantation was trialled in advanced breast cancer. However, it appears that this therapy, which is very toxic, is no better than standard chemotherapy.
Many thousands of women are entering various clinical trials of newer drugs that are being continuously developed. In this way over the last few decades the outlook for women with breast cancer has been dramatically improved, with a significant reduction in deaths.
Breast prosthesis and reconstruction
Fortunately many women can now avoid mastectomy and loss of the breast. However, for those who require mastectomy this can be emotionally traumatic. After the loss of a breast, many women feel quite depressed, even humiliated, and require sympathetic help and understanding.
Prosthetic breast padding has improved, and types are now available that allow normal activity, even swimming, without detection. In other cases plastic or reconstructive breast surgery may be considered. These procedures are usually not advised until at least a couple of years after mastectomy, in order to be as sure as possible that recurrence of the cancer is unlikely. On the other hand, some specialised plastic surgeons are now offering reconstructive surgery to replace the breast immediately after its removal. Such procedures offer considerable emotional benefit to some women.
Emotional support and the understanding of family and friends are essential for most women who have had breast cancer, even if they have not had a mastectomy. As breast cancer is one of the most common cancers in Western societies, many cities have mastectomy support groups that women are welcome to join, and company and advice from group members can be of great help. Local state cancer councils can advise on the contact details of such support groups.
CANCERS OF THE DIGESTIVE SYSTEM
Cancer of the oesophagus
The oesophagus is the hollow food passage that passes from the mouth and pharynx through the chest to the stomach (in the abdomen). Cancer of the oesophagus is a common disease in Asian and some African countries, as well as Russia and Scandinavia, but is less common in people of Anglo-Celtic origin. The reason for this difference in incidence is not fully understood, but diet plays a significant role. Northern China has a very high incidence, caused by a fungus that grows on poorly stored food. Cancer of the oesophagus is more common in men, particularly those who smoke and drink alcohol to excess. Oesophageal cancers in men are usually in the middle or lower oesophagus. Cancers in the upper oesophagus are more common in women.
There are two types of oesophageal cancer. The commonest is squamous cancer in the upper or middle oesophagus, and the other is adenocarcinoma, which occurs in the lower oesophagus close to the junction with the stomach.
Symptoms and signs
Unfortunately, cancer of the oesophagus is often relatively advanced at the time of diagnosis. The most common symptom is difficulty with swallowing. This is first noted when swallowing solids, which seem to get caught in the throat or chest. Later there is difficulty in swallowing liquids. A person with cancer of the oesophagus will soon lose weight, become quite wasted and even dehydrated.
Investigations
Barium-swallow or barium-meal X-rays (see Section 2) will usually show an obstructive or irregular narrowing at the site of the cancer.
Oesophagoscopy is carried out and the doctor can usually see an irregular or ulcerated cancer. A biopsy is taken to establish the diagnosis by microscopic examination.
Unfortunately, cancers of the oesophagus will have often spread up and down the mucous membrane (lining) of the oesophagus and into lymph nodes and other structures in the chest before the patient notices many symptoms. Thus, by the time the patient has consulted a doctor the cancers generally have a relatively low cure rate.
Treatment
The best hope of cure is by surgery. The oesophagus is removed and either the stomach or a section of bowel is used as a replacement for the passage of food.
In some cancer-treatment clinics chemotherapy or combined chemo/radiotherapy is used prior to attempts at curative surgery. Studies are being made in a number of world centres to determine which combinations of chemotherapy and radiotherapy and surgery achieve best results. Although the outlook for people with oesophageal cancer must still be circumspect, more encouraging results are being reported from some centres.
Sometimes it is not possible to attempt to remove the cancer, and the most helpful treatment is for the surgeon to pass a plastic tube (stent) through the oesophagus into the stomach to allow the patient to swallow food. Otherwise, some alternative food passage (such as a transplanted section of bowel) or another method of feeding may be required. Radiotherapy, sometimes combined with chemotherapy, may be used in this palliative way. This can result in cancer shrinkage, often relieving symptoms for a time.
Cancer of the stomach
Cancer of the stomach was once one of the most common cancers in the Western world but is no longer so. Stomach cancer is uncommon before the age of 40 years but increases in incidence with age, reaching a peak between the ages of 60 and 65. Males are affected about two or three times more commonly than females.
Cancer of the stomach has a distinct racial or geographic association. It is about seven times more common in Japan and Korea and three or four times more common in Eastern Europe than it is in Australia or the USA. Epidemiological studies suggest that it has a direct relationship to diet. People who have a diet high in animal fats and low in fresh fruit and vegetables are at greater risk of stomach cancer. It may also be related to a high intake of chemical food preservatives and food subject to other methods of preservation and preparation, such as the smoking of fish or meat. The high intake of smoked fish in Japan has been incriminated; there is also a high incidence of this cancer among the people of northern Iceland, who eat large amounts of crude smoked salmon, whereas there is a lower incidence in the people of southern Iceland, who have a different diet. In Korea the custom of eating a great deal of red pepper and possibly other spices in food is thought to be significant in increasing the risk.
The decreasing incidence of stomach cancer in modern industrialised societies appears to be the result of the greater availability of fresh fruit and vegetables due to improved transport and the use of refrigeration rather than chemical preservatives, additives or smoking.
There are also a number of rare conditions that result in a higher risk of stomach cancer: pernicious anaemia, chronic gastritis, polyps in the stomach and possibly gastric ulcers. Tobacco smokers also have an increased risk compared to non-smokers.
Symptoms and signs
Like cancer of the oesophagus, stomach cancer is often quite advanced before pain or other symptoms are noticed. The earliest symptom is usually some vague indigestion that gradually becomes worse. Persistent indigestion occurring for the first time in someone over the age of 40 years must always be considered with suspicion.
Sometimes an early feature is loss of appetite, especially for certain foods, particularly meat. Other symptoms may be a feeling of being full or even feeling ‘blown up’ in the stomach after eating small amounts of food, or vomiting after food, particularly if vomiting becomes frequent or regular. This may indicate blockage of the outlet of the stomach. Pain is sometimes the first symptom, but, as mentioned, when pain is persistent, the cancer is often quite advanced. Some patients may actually vomit fresh blood (haematemesis).
Sometimes a patient may not be aware of any symptoms but has found a lump in the upper abdomen. In others complaints of weakness and tiredness due to anaemia or recent unexplained weight loss may have caused the patient to seek medical attention. Occasionally the first evidence of illness is caused by the cancer spreading to other organs, presenting an enlarged liver or jaundice. Pain in the back can be caused by the cancer spreading to the pancreas or into lymph nodes behind the stomach.
The doctor will look for a swelling or lump in the abdomen, evidence of an enlarged liver or lymph nodes (especially an enlarged lymph node in the left side of the neck), evidence of spread into the pelvis or an ovary (felt on vaginal or rectal examination), and evidence of fluid in the abdominal cavity. There might also be weight loss or anaemia (due to the cancer bleeding into the stomach cavity).
Investigations
The doctor may test for blood in the faeces or test the blood for iron-deficiency anaemia or other abnormalities.
Gastroscopy (see Section 2) is now commonly performed as a first investigation. Through a gastroscope a cancer may be seen as an ulcer with raised edges, a mass or a rigid abnormal distortion of the stomach wall. A biopsy can also be taken to confirm the diagnosis. This is necessary to distinguish gastric cancer from other cancer types, such as gastric lymphoma.
Barium-meal X-ray films and screening may show an ulcer (usually with raised, rounded edges) or a lump on the stomach wall looking something like a small cauliflower. The X-rays and screening may alternatively show a blocked stomach, a change in the stomach’s shape or size (bigger or shrunken and smaller), or a more rigid and stiff-walled stomach. However, X-rays will not show all cancers in the stomach, and other tests are also needed. However, since gastroscopic examinations have become reliable and easily performed, these radiological investigations are now done less commonly.
CT scans may be useful to determine the size, extent and spread of a gastric cancer (e.g. spread into the pancreas behind the stomach, into adjacent lymph nodes or into the liver).
Treatment
The only potentially curative treatment for cancer of the stomach is surgery in which the stomach is completely removed (total gastrectomy), mostly removed (sub-total gastrectomy) or partly removed (partial gastrectomy).
If a cancer has already spread beyond the stomach, cure may not be possible, but it may still be possible to give the patient relief of symptoms by a bypass operation to relieve blockage.
After total gastrectomy the small intestine is joined to the oesophagus or, in the case of a sub-total or partial gastrectomy, the small intestine is joined to the remaining part of the stomach to allow food to pass through normally. With no stomach present or only a small part of the stomach present, the patient can eat only small meals and therefore needs to eat frequently to avoid excessive weight loss. Without a stomach the patient may also develop a form of pernicious anaemia. This can be prevented by injections of vitamin B12.
The results of surgery alone in treating stomach cancer have been disappointing in the past. In general the smaller a cancer is at surgery the better the results. For this reason, gastroscopy and other diagnostic tests may be used to look for evidence of cancer as soon as a patient complains to a doctor of early symptoms, especially if the patient is a male over the age of 40 years. In some countries, and especially in Japan where stomach cancer is common, screening tests are often carried out for people at risk even if they do not have any symptoms. If stomach cancers are found while they are small and in the early stages (as is now often the case in Japan), the results of treatment by operation are good, with a high rate of cure. However, this is not often the case in Western societies, where stomach cancer is less common and is not often diagnosed until troublesome symptoms have developed, by which time the cancers are advanced and unlikely to be cured by surgery alone.
Anti-cancer drugs do not cure this cancer, but they may be useful in treating people whose cancers cannot be cured by operation. The drugs will often make the cancers smaller and may give the patients good relief, possibly for several months.
More recently, anti-cancer drugs have been given to some patients before the operation (induction or neoadjuvant chemotherapy, see Section 2). There is some evidence that if the cancers are made smaller by the drugs before a gastrectomy is carried out, the results and the chances of cure will be better. Often chemotherapy may be given after surgery if the lymph nodes are involved, and this has been shown to improve chances of survival.
In some cancer centres studies are under way to determine whether giving the drugs pre-operatively by direct infusion into the artery that supplies blood to the stomach results in more effective reduction of the cancer before surgery.
Cancer of the liver
Primary liver cancer (hepatoma)
Cancer starting in liver cells (primary cancer) is uncommon in ethnic Europeans but is a major problem in Africans, South East Asians, Chinese and Japanese. It represents some 50% of all cancers in African Bantu men. These differences appear to reflect hygiene, diet and food-storage practices. Chronic liver infection due to hepatitis B and hepatitis C is responsible for much of the increased incidence in Asia. Certain fungi-producing toxins (aflatoxins) and contaminated food in parts of Africa also play a major role.
Primary liver cancer also sometimes develops in people with longstanding cirrhosis (a fibrotic degeneration) of the liver, as a result of excessive alcohol consumption or other causes, and this is the most common cause in Western countries.
Symptoms and signs
The first evidence of primary liver cancer may be general ill health (loss of appetite, weight loss, weakness and debility) or liver enlargement with pain in the upper abdomen, swelling, jaundice or fluid in the abdominal cavity (ascites).
Investigations
Investigations that may help include CT scans, ultrasounds, sometimes arteriography and especially liver biopsy. Blood tests for liver function, for anaemia and for blood-chemical changes are often helpful too. A special blood-tumour marker test called alpha-feto-protein estimation usually gives an elevated reading in people with this cancer; it usually falls to normal levels if the cancer has been cured. Progressive alpha-feto-protein tests may thus give useful evidence of the effectiveness of treatment.
Treatment
The treatment of hepatoma is only successful if the disease is detected when it is confined to a part of the liver that can be removed by surgical operation. Unfortunately, as the cancer has usually spread widely in the liver when first detected, cure is usually not possible. It is possible, however, to prolong life, sometimes for many months, by injecting cancer masses in the liver with cold alcohol, microwave needle probes or with freezing probes (cryosurgery). In some patients a catheter can be placed in the main artery to the liver and injected with either chemotherapy or radioactive micro-beads. This can cause shrinkage of the cancer and relief of symptoms, and occasionally, but very rarely, the cancer can then be resected.
Secondary (metastatic) liver cancer
Although primary liver cancer is uncommon in people of European races, the liver is one of the most common sites of secondary cancer in all races, including Europeans. Cancers of the digestive tract, especially the stomach, pancreas, colon and rectum, commonly spread via the bloodstream to the liver. Cancers of almost any other tissue may also spread to the liver, but breast cancer, lung cancer and melanoma are especially likely to do this.
Secondary cancers in the liver cause it to enlarge. It may become uncomfortable or even painful; jaundice often develops and fluid may accumulate in the abdominal cavity. A person with secondary liver cancer sooner or later notices loss of appetite, loss of weight and loss of energy. Breathlessness may also be a symptom.
Investigations
The doctor will look for the features mentioned above and may arrange investigations to help establish the diagnosis. The most helpful investigations are usually a CT scan, ultrasound and sometimes arteriography. A liver biopsy, either carried out with a special needle through the lower chest or abdominal wall under local anaesthesia or done during an operation, may be required to be sure of the diagnosis. This biopsy is not always needed if a primary cancer has been previously recognised, however.
If the site of a primary cancer that has spread to the liver is not known, investigations may sometimes be carried out to discover where the secondary cancer in the liver originated. Various blood tests can help in this situation.
Treatment
Secondary cancer in the liver is usually not curable. A potential for cure exists if there are a small number of secondaries in one part of the liver that can be surgically excised. However, this is not common. In most people the secondary cancers are spread throughout most parts of the liver.
For patients with liver metastases that cannot be surgically excised many approaches to treatment have been used. If the primary cancer is known to be sensitive to chemotherapy (e.g. breast cancer, lymphoma, testicular cancer, colorectal cancer), then the various drug combinations that are known to be effective in these diseases can be used. Alternative therapies have included direct intra-arterial infusion of cytotoxic drugs via a small catheter placed in the hepatic artery, which supplies blood to the liver. This can be connected to a small pump that can be placed under the skin in the anterior abdominal wall. It is possible for these pumps to infuse medication over many months. In some patients this can lead to significant shrinkage of the cancers and improvement in quality of life.
It is also possible to carry out what is called chemo-embolisation, in which micro-beads are combined with chemotherapy and injected via catheter into the hepatic artery. Similarly, radioactive micro-beads can also be injected via the catheter.
Other alternatives are radio-frequency ablation via microwave probes directly inserted into liver metastases, alcohol injections into the metastases and injection of the metastases with a freezing probe. This freezing probe causes the secondary cancer deposits to be frozen, and the cells are killed when the freezing thaws.
An approach being studied in some highly specialised surgical oncology centres is for the surgeon to isolate the liver from the general body circulation and infuse very high doses of chemotherapy into the liver circulation for an hour or so. From early studies some temporary success has been reported using this treatment, but no long-term cures are apparent as yet.
For most patients the disease will subsequently progress and ultimately prove fatal. However, with some simple measures it is possible to make the last weeks and days of such patients really quite comfortable. Corticosteroid drugs are very effective at relieving the pain and tenderness associated with the liver-capsule distension, and various morphine derivatives will also relieve pain and give a sense of wellbeing.
Cancer of the gall bladder and bile ducts
These are relatively uncommon cancers in Western countries although quite common in parts of some countries, such as southern India. Cancer of the gall bladder is usually associated with gallstones (cholelithiasis) that have been present for many years, particularly in older women. By contrast bile-duct cancer is slightly more common in men.
The removal of gall bladders with gallstones, especially in young women, is often recommended to reduce the risk of subsequent cancer.
Early cancer may occasionally be found unexpectedly on pathological examination of the gall bladder after it has been removed for chronic inflammation or gallstones. In such cases cure of the cancer may have been achieved simply by the removal of the gall bladder.
If it is not diagnosed early, cancer of the gall bladder may cause persistent pain in the upper right side of the abdomen, with evidence of inflammation of the gall bladder, or it may cause a swelling or lump felt in the upper abdomen under the ribs on the right side.
The first indication of cancer of the gall bladder, and more especially cancer of the bile ducts, may be jaundice due to the blockage of the flow of bile from the liver. The jaundice is often accompanied by a severe itch of the patient’s skin.
Cancer of the gall bladder tends to spread into the liver as well as into nearby lymph nodes. Once this has happened, it is virtually incurable by surgery and does not respond well to radiotherapy. It also has a reputation for not responding well to chemotherapy, although good response to intra-arterial chemotherapy (see Section 2) and cure with following surgery has been reported. In advanced cases jaundice and itch, if present, can usually be relieved by an operation in which the obstruction to bile flow is bypassed, allowing the bile to flow into the small intestine by another route.
Cancer of the pancreas
Cancer of the pancreas has become increasingly common in Westernised societies over recent years. It is now the fourth most common cause of cancer death in males in Australia and the third most common cause of cancer death in males in the US. Although it is slightly more common in men, its incidence is similar in both men and women. Risk factors for its development include smoking, diabetes, chronic pancreatitis, obesity and a high-fat diet.
Symptoms and signs
Cancer of the pancreas often invades or compresses the bile duct draining from the liver, as it passes through the pancreas. As the cancer grows, it commonly blocks the bile duct, obstructing the flow of bile from the liver into the intestine and resulting in jaundice. The level of jaundice may be quite intense. The jaundice is sometimes painless, although there is often pain felt deep in the upper abdomen and passing through to the back. As the jaundice develops, the patient’s skin may become very itchy. The liver and gall bladder often become enlarged due to obstruction of the bile duct. Occasionally the cancer can be felt as a lump in the upper abdomen.
Weight loss may be the first feature of this disease. Anorexia (loss of appetite) is usual, and diarrhoea may also be present.
Investigations
As the pancreas lies across the back of the upper abdomen behind the stomach and other organs, it has been difficult in the past to examine or investigate. However, in recent years improved methods of investigating and imaging the pancreas have become available.
Ultrasound, CT and MRI scans have been of some help in detecting cancers, although early detection of the smaller and potentially curable cancers before they cause symptoms is rare.
Examination of the pancreatic duct using an endoscope passed orally and through the stomach into the duodenum (ERCP examination) has allowed pancreatic secretions to be examined for cancer cells and X-rays to be taken of the duct. These may be helpful in detecting evidence of some pancreatic cancers at an early stage.
PET scanning using a glucose product (fluorodeoxyglucose) as a tracer appears to be highly successful in identifying pancreatic cancer localisation (see Section 2). The serum marker CA19.9 is also helpful in diagnosis and in management.
Needle biopsy of any lump in the pancreas under CT guidance is the most useful method of establishing a diagnosis, although this procedure does have risks and is not always reliable.
Treatment
At the time of detection cancer of the pancreas has often spread to the liver as well as to lymph nodes and cure by surgery is no longer possible. However, some small cancers can be resected in a major surgical operation with some prospect of cure. In some cancer-treatment clinics a combination of chemotherapy with radiotherapy is used prior to surgery to improve the chance of complete surgical removal (induction or neoadjuvant therapy). Alternatively, this treatment may be given after surgery. In some highly specialised surgical oncology centres some success has also been reported with chemotherapy given by intra-arterial infusion before surgery.
For those suffering jaundice due to pancreatic cancer obstructing the bile duct, relief can usually be achieved by a surgical operation in which the obstruction to the bile duct is bypassed.
Cancer of the small intestine
Cancer of the small intestine is rare. The most common of the rare primary malignant tumours of the small intestine are a lymphoma and a tumour called a carcinoid (cancer-like) tumour. These are rare causes of abdominal pain, bowel bleeding and small bowel obstruction. They are usually treated by a surgical operation in which the tumour is removed along with part of the bowel.
Carcinoid tumours may occur anywhere in the alimentary (digestive) tract. That is, they may occur anywhere between the mouth and the anus. However, the most common site of a carcinoid tumour is the appendix. Most carcinoids in the appendix (and in fact most small carcinoids) are not malignant. Sometimes when an appendix has been removed, a small carcinoid tumour may be found in it. In most such cases the tumour has been cured by removal of the appendix and further treatment is not necessary.
When a carcinoid tumour is found in the small intestine, it is more likely to be larger, more likely to be malignant and may have already spread to the liver. Secondary carcinoids in the liver may release certain biochemical substances that can cause bouts of diarrhoea, flushing of the skin of the face or wheezing of the lungs. Treatment can be given to control these episodes, but once this tumour has spread into the liver a complete cure is unlikely.
A rare tumour originating in connective tissue is the so-called gastrointestinal stromal tumour or GIST. This tumour has an unusual protein (called a mutated signal receptor) on its cell surfaces and responds dramatically to a new ‘targeted’ drug called Glivec. The drug specifically inhibits the abnormal receptor, blocking transmission of growth signals in the tumour cells, thus stopping cancer-cell division. This drug is given orally. It is also extremely effective in treating chronic myeloid leukaemia.
Cancer of the large bowel
In Western societies the large bowel is the most common site of primary cancer other than skin cancer. In the adult populations (both male and female) of Australia and New Zealand bowel cancer is responsible for more deaths than any other cancer. In the adult population of the USA lung cancer causes more deaths but bowel cancer is next.
Bowel cancer is occasionally seen in young adults and even in children but is not commonly seen until after the age of 40 years. Thereafter the incidence rises with age, reaching a peak between 60 and 75.
As discussed in Section 1, cancer of the large bowel is most common in societies where the food intake is relatively high in meat and animal fats and relatively low in fibre. Fibre is a greater component of wholemeal grains, fruit and vegetables.
Polyps in the large bowel also predispose people to cancer and, if present, should be removed to avoid the risk of malignant change. People who have had polyps removed should be kept under regular colonoscopy observation in case more develop.
The uncommon hereditary condition familial adenomatous polyposis is one in which about half of the members of an affected family are likely to develop multiple polyps. It is a highly pre-malignant condition, and all close blood relatives in an affected family should be kept under regular observation. If polyps are found, the large bowel should be removed to prevent the development of cancer later in life. If this is not done, most people will have developed a bowel cancer by the age of about 40 years.
Other conditions associated with an increased risk of large-bowel cancer are the inflammatory bowel diseases ulcerative colitis and, to a lesser extent, granular (Crohn’s) colitis. People with longstanding and extensive ulcerative colitis must be kept under close and regular observation and in some circumstances may be well advised to have the colon removed as a precautionary measure.
Close relatives of any patient with large-bowel cancer have a slightly increased risk of developing a similar cancer. This is termed hereditary non-polyposis colorectal cancer, reflecting a specific gene mutation. There are also rarer genetic syndromes leading to colorectal cancer.
After successful treatment of one large-bowel cancer, the patient has a rather greater than average risk of developing a second cancer in the large bowel, although by far the majority of such patients never develop a new cancer. However, regular follow-up observation is desirable for all patients after treatment for bowel cancer, as for all patients treated for other types of cancer. It is standard practice for patients to have a follow-up colonoscopy within the first 12 months following surgery for colorectal cancer. This is to ensure that a second cancer or polyps are not missed.
Symptoms and signs
The most common symptoms associated with large-bowel cancer are a change in bowel habits (constipation or diarrhoea or alternating constipation and diarrhoea), rectal bleeding or a feeling of incomplete evacuation of the rectum after going to the toilet. Some patients may not notice any symptoms until the cancer has caused bowel obstruction. This may cause abdominal colic, constipation and abdominal distension.
Other features of large-bowel cancer may be debility, weight loss, tiredness and lassitude (sometimes due to anaemia) or features of liver enlargement with jaundice due to liver metastases.
The doctor may be able to feel a lump or localised swelling in the abdomen or, on examination through the anus, a mass in the rectum. There may be evidence of blood in the faeces. In the case of obstructive bowel cancer, evidence of bowel obstruction with abdominal distension or swelling may be found.
Investigations
Investigations that may help in establishing a diagnosis include examination with a flexible sigmoidoscope through the anus. About 50% of large-bowel cancers are in the rectum or the lowest part of the colon just above the rectum, and most of these can be seen and biopsied through the sigmoidoscope. This can be done as an outpatient procedure (see Section 2).
Examination with a fibre-optic colonoscope, however, requires sedation or possibly an anaesthetic, but this examination will allow the whole length of the large bowel to be examined visually and for biopsies to be taken from any part of the length of the colon. These are performed in day-care outpatient centres. Less commonly, barium enemas are done to visualise the colon and rectum.
Blood studies are carried out for evidence of anaemia and changes in biochemistry of the blood or impaired liver function. One particular blood test useful for the diagnosis, management and study of a patient with large-bowel cancer is the carcinoembryonic antigen (CEA) test. This test is usually strongly positive in people with large-bowel cancer and becomes negative after successful treatment. If it becomes positive again after treatment, it may suggest recurrence of the cancer.
CT scans may also be done to look for any evidence of secondary liver cancer.
Treatment
Large-bowel cancer requires surgery to remove that part of the bowel containing the cancer together with draining lymph nodes into which the cancer may have spread. Generally the bowel is joined together again (anastomosed) and the patient can return to normal life.
When the cancer is very low in the rectum, it may be necessary to remove the anus as well as the rectum; in this case an opening (colostomy) for the lower bowel is made in the abdominal wall to allow evacuation of faeces. The patient wears a bag over the colostomy, and the bowel empties at regular intervals into the bag. The patient learns to empty the bag at convenient times and recovers to live an active and virtually normal life.
Colostomy associations or groups have branches in many large cities. These groups offer support and advice on learning to live with a colostomy and the other social adjustments that may worry patients.
In the hands of specialist colorectal surgeons, and depending on the stage of the tumour, some 50–75% of patients will be cured. With or without a colostomy most of these then return to normal life.
If a cancer first appears with a bowel obstruction, it may be necessary to perform a temporary colostomy to relieve the obstruction. Usually the cancer is removed at a further surgical operation three or four weeks later, and the colostomy is closed, resulting in a return to a normal passage of bowel actions.
The outcome for patients with colorectal cancers has improved significantly in recent years. An advance in rectal cancer has been, for some patients, treatment prior to surgery with a combination of chemotherapy and radiotherapy. This has reduced the need for a colostomy as well as reducing the risk of local recurrence of the cancer in the pelvis. A second major advance has come from clinical trials using some of the newer anti-cancer drugs after surgery in patients who are found to have lymph-node involvement. These have reduced the chance of metastatic disease spread or recurrence. This is a form of adjuvant chemotherapy (see Section 2).
Follow-up care
As for all patients who have had treatment for cancer, regular follow-up consultations and care are required for patients who have had a bowel cancer removed. A follow-up colonoscopy is usually done within a year of the operation. There is always a risk of secondary cancer showing up in the liver or elsewhere, and there may be a risk of another cancer developing, which can be effectively treated if detected while still small. In the case of bowel cancer, any secondary cancer usually shows up within two years; it is uncommon for it to appear after five years. If the patient has been followed up for five years without evidence of recurrence, he or she is usually considered to be cured.
If the cancer has spread to the liver, cure is rarely possible except, for example, in occasional cases where there is a small number of metastases that can be surgically resected.
Secondary spread to the liver can sometimes be controlled for up to two to three years with the newer types of chemotherapy. The recent development of an implantable pump to continuously infuse cytotoxic drugs into the artery supplying blood to the liver has shown encouraging results as far as improving the patient’s quality of life and life expectancy are concerned but is very rarely curative.
Cancer of the anus
Cancer of the anus is not common but may present as a lump, an ulcer, bleeding or pain in the anal region. Sometimes it may develop in a pre-existing benign lesion such as a papilloma (a fern-like growth from the bowel lining), a patch of leukoplakia (white patch) or in a longstanding anal fissure (a split in the wall of the opening of the anus).
Most cancers of the anus are similar in type to SCC of skin but behave more aggressively in that they tend to spread to lymph nodes in the groin or pelvis at an earlier stage and often require radical treatment to achieve the best chances of cure.
Treatment
A biopsy is taken to confirm the exact diagnosis. Treatment is generally a combination of chemotherapy and radiotherapy over several weeks as an outpatient. This approach has a high cure rate. This means extensive surgery and a colostomy can be avoided in many patients unless they present with very advanced disease or have not completely responded to the course of chemotherapy and radiotherapy.
CANCERS OF THE HEAD AND NECK
Cancers of the lips, mouth, tongue, nasal cavity, the paranasal air sinuses, throat, larynx and pharynx (the passage at the back of the nose and mouth) constitute about 5% of all cancers encountered in Western countries. Most of these cancers are similar pathologically to SCCs of the skin but tend to behave in a more malignant and aggressive fashion. As a rule, the further away the cancers are from the lips the more aggressively they behave.
Smoking is the major cause of this group of cancers. It has been estimated that cancers in the mouth and throat are about six times more common in smokers, and this is increased to about 15 times if the smokers are also heavy consumers of alcohol. Other pre-malignant conditions that predispose to cancer in the mouth include leukoplakia, papillomata and chronic irritation from such causes as ill-fitting dentures or jagged teeth (see Section 1). Cancer of the buccal mucosa (cheek lining) is common in India and South East Asia, where betel-nut chewing is a common practice. It is especially common in people who mix betel-nut with tobacco leaf or lime and hold the mixture in the cheek pouch.
Cancers of the lips
Because of their high visibility cancers of the lips are usually diagnosed at an early, potentially curable, stage. They may develop as a thickening in an area of hyperkeratosis (sun damage), more often on the lower lip. They tend to ulcerate, possibly bleed, or may form a lump. They may later spread to lymph nodes under the jaw and in the neck, where they may form palpable lumps.
A biopsy is taken to confirm the diagnosis, and thereafter treatment is usually by surgical excision, with good results both cosmetically (in appearance) and in eventual cure rates. Radiotherapy may also be used with good results.
For larger cancers of the lips, either radical surgery removing a large part of the lip (with some form of plastic or reconstructive surgery to fashion a new lip) or radiotherapy may be used, and the chances of cure are still quite good.
If hard enlarged lymph nodes are present either when the patient is first seen or at a later follow-up visit to the doctor, then these are best treated by a surgical excision known as a block dissection (an operation to remove all lymph nodes in one block of tissue).
Occasionally a patient first consults a doctor when the cancer is very large and ulcerating and possibly the whole of the lip is involved with cancer. In these patients considerable success can be achieved with induction chemotherapy prior to surgery or radiotherapy. If the expertise is available, pre-operative chemotherapy given by intra-arterial infusion is even more effective in reducing very advanced cancers to smaller cancers that will be more curable by surgery or radiotherapy, or if necessary both (see Section 2).
Cancers of the floor of the mouth (under the tongue), anterior two-thirds of the tongue and buccal mucosa (inside the cheek)
These cancers are more aggressive than lip cancers, growing and spreading more rapidly, and the enlargement of lymph nodes containing secondary spread of cancer is rather common.
The cancer is usually first noticed as an ulcer or a lump, sometimes by a dentist, before the patient has become aware of any problem. Other common features are bleeding or localised soreness. Such cancers tend to be on the surface at first but soon invade locally, with firm thickness and induration surrounding the lump or ulcer. They usually become quite tender. Diagnosis is confirmed by taking a small piece of tissue as a biopsy for examination under the microscope.
Most of these cancers are treated by surgical excision or radiotherapy. Lymph nodes are best treated by surgical excision of all lymph nodes in the region (block dissection).
For larger cancers in the floor of the mouth, anterior two-thirds of the tongue and possibly in the cheek, treatment by a combination of chemotherapy and radiotherapy may be required. By these simultaneous combined treatments, or alternatively if the chemotherapy can be given by intra-arterial infusion, cures can now be achieved in patients with advanced cancers that until recently were considered incurable or curable only by the most radical surgery. Such treatments require special skills, equipment and experience and should only be carried out in specialist cancer centres.
Cancers in the posterior third of the tongue, tonsillar region and pharynx
People with these cancers may present with an ulcer, a lump in the throat or tongue, or sometimes with a constant sore throat that has not responded to medical treatment, including antibiotics. Sometimes patients will first notice a lump in the side of the neck, which is an enlarged hard lymph node containing secondary cancer. Diagnosis may appear to be obvious but must be confirmed by biopsy.
Except for small cancers in this region, most are not curable by surgery. Radiotherapy is likely to cure only small cancers, although it may offer good temporary palliation to people with large cancers.
Most people with these cancers do not visit a doctor or clinic until the cancer is advanced and the chances of cure by surgery or radiotherapy are not good. Most will be heavy smokers, and many will also be heavy alcohol drinkers. They may not notice the symptoms until the cancers are at a late stage. In any case, these cancers are aggressive and tend to grow and invade locally and spread into lymph nodes on one or both sides of the neck at a relatively early stage.
Radical surgery will cure some of these patients, but cure is more likely to result from combined chemotherapy and radiotherapy, with or without following surgery. For incurable cancers combined therapy will at least give good palliation to the majority. The chemotherapy and radiotherapy may be given simultaneously as chemo/radiotherapy or may be given over a more prolonged period – first giving the chemotherapy, preferably by intra-arterial infusion, followed later by radiotherapy. Special experience, skills and facilities are required for these procedures, so the most appropriate treatment will depend on the skills and experience of the treatment team (see Section 2).
Cancers of the post-nasal space (back of the nose)
These cancers are most common in adult Chinese people, especially those from the Guangdong province of China. Immigrant descendants of these people have an increased incidence of this cancer, even though they may never have lived in China.
Blood tests show that this cancer is most common in people who have been infected with the Epstein-Barr virus: their blood usually has a high level of Epstein-Barr-virus antibodies. If the Epstein-Barr test is high before treatment and returns to normal after treatment, it indicates that treatment has been successful and the patient has probably been cured.
Symptoms and signs
People with post-nasal-space cancer may present with symptoms of a blocked nose and nasal or post-nasal discharge of mucus, pus or bloodstained material. Alternatively, they sometimes first notice a lump in the side of the neck. The lump is due to secondary cancer in a lymph node. Sometimes lymph nodes on both sides of the neck are involved.
The cancer may sometimes be seen with a mirror in the back of the throat, but diagnosis is made by taking a biopsy from the back of the nose or sometimes by removing an enlarged lymph node from the neck for pathological examination.
Occasionally the cancer invades bones at the base of the skull or the cranial nerves that pass from the brain through the base of the skull and into the neck. CT or MRI scans may be taken to look for evidence of bone involvement.
Treatment
Cancer in the back of the nose is not accessible to surgery. It is usually treated by radiotherapy, with better than a 50% chance of cure provided the cancer has not spread into lymph nodes in the neck or invaded bone behind the nose at the base of the skull. If lymph nodes in the neck are involved, the chance of cure by radiotherapy alone is reduced (possibly to only 30–40%) and considerably lower if nodes on both sides of the neck are involved. However, combined integrated chemotherapy and radiotherapy (see Section 2) has improved the outcome in advanced cancers, especially if lymph nodes are involved.
If bone at the base of the skull is invaded by cancer, the chance of cure by any means is poor.
Cancer of the larynx
Cancer of the larynx is most common in smokers, especially smokers who are also heavy drinkers. It is more common in men than women. The most common site is on a vocal cord, which can cause hoarseness or change in the voice when the cancer is small and is therefore usually diagnosed early. They can be seen and biopsied through a laryngoscope. If treated early, either by radiotherapy or by surgery (in which the cord is removed), the results of treatment are good, with a 90% cure rate.
If neglected until the cancer has grown from the vocal cord into surrounding tissues, however, the chances of cure by simple surgery or radiotherapy are much reduced.
For the more advanced laryngeal cancers that have spread to the walls of the larynx or spread into lymph nodes in the neck, or cancers that have recurred after previous radiotherapy, the best chance of cure is by radical surgery in which the larynx is removed, possibly together with all draining lymph nodes (an operation called a radical laryngectomy).
Cancers in the larynx that develop above or below the vocal cords are usually more advanced when they are first diagnosed than cancers on a vocal cord. They also tend to be more aggressive and for this reason are often treated by combined radiotherapy and laryngectomy or even combined chemo/radiotherapy and laryngectomy.
After removal of the larynx, the chance of cure is reasonably good, but the patient (usually a male) is left with an opening in his windpipe in the lower neck (a tracheotomy). Without a larynx he cannot speak normally, but most patients learn a form of oesophageal speech. By this method they can be taught to swallow air and regurgitate air from the stomach to make sounds and words. Alternatively, a mechanical vibrator powered by a small battery can be applied to the throat muscles to make speech that sounds rather like the artificial voice of a robot or computer.
The Lost Cords club is a group for people who have lost their larynx and support each other in learning to speak and in other social, health and mechanical problems. As with mastectomy groups (for women who have had a breast removed) and colostomy groups (for patients with a colostomy), there are branches in many big cities. The group helps people who have had a laryngectomy to adjust to their changed circumstances. It also helps patients learn to speak so that they can live a relatively normal life again.
Salivary-gland cancers
The salivary glands are located about the mouth and secrete saliva into the mouth to prepare food for digestion. There are three major and many minor salivary glands on each side of the face.
The largest salivary gland is the parotid gland, situated partly in front of and below the ear and behind the jaw. This is the salivary gland in which both benign and malignant tumours develop most commonly. The second-largest major salivary gland is the submandibular gland under the jaw, and the third major salivary gland is the sublingual gland in the floor of the mouth under the tongue. The many small minor salivary glands are in the mucous membrane (lining) of the tongue, lips, palate, cheek and pharynx.
Cancers of the salivary glands are usually first noticed as a lump, most commonly just in front of or below the ear. As the cancer enlarges, it may invade and destroy the important facial nerve, which passes through the parotid gland. Damage to the facial nerve causes weakness of the muscles of that side of the face, resulting in an inability to close the eye or move the corner of the mouth properly. There may be obvious loss of facial expression due to paralysis of the muscles on that side of the face. These cancers most often develop in middle-aged or older adults. They enlarge locally and tend to spread to local lymph nodes in front of the ear and in the upper part of the neck. Occasionally cancers develop from a pre-existing benign tumour in the parotid gland that may have been present for years, known as a mixed parotid tumour or pleomorphic adenoma.
Treatment of cancers of the parotid gland is usually by removal through a surgical operation. With small cancers it may be possible to save the facial nerve, but with larger cancers it is likely that the facial nerve will be involved and will need to be removed. If lymph nodes are enlarged, they are usually removed in the same block of tissue with the parotid gland. Post-operative radiotherapy is often given in view of the risk of local recurrence of these cancers.
Cancers in the submandibular and sublingual salivary glands are not common, but when present they tend to spread rapidly to lymph nodes and are best treated by surgical excision of the whole of the gland, together with any involved lymph nodes. Salivary-gland cancers also occasionally occur in the minor salivary glands, either in the tongue, in the cheeks, lips or elsewhere about the mouth. Wide surgical excision is required for treatment as the chances of local recurrence are high unless a lot of tissue around the lump is removed. If there is any doubt that the cancer has been totally removed, then radiotherapy may also be given after the operation.
Chemotherapy in the treatment of salivary-gland cancers has generally not been of benefit, although success has been reported in treating locally aggressive cancers using regional-induction chemotherapy before surgery.
Cancer of the thyroid gland
The thyroid gland lies across the lower part of the neck, with one lobe on either side of the trachea (or windpipe) and on the lower part of the larynx (voice box). The thyroid gland uses iodine to make a hormone called thyroxine, which is essential for normal body function.
Enlargement of the thyroid gland is called a goitre, and multiple cysts and other lumps may develop in some goitres. This process is usually due to a shortage of iodine in the food. A lumpy goitre is known as a multinodular goitre.
Occasionally one of the lumps in a multinodular goitre will become malignant and form a cancer, but more often a cancer develops as a single lump in an otherwise apparently normal thyroid gland.
Thus cancer of the thyroid is usually first noticed as a single lump in the thyroid gland, most often just to one side of the midline in the lower part of the neck. It may occasionally develop in a goitre as one lump that enlarges and becomes more obvious and hard.
Investigations
An isotope scan is a useful investigation for thyroid cancer. A scan of the thyroid is taken after injection of a very small dose of radioactive iodine into a vein (see Section 2) and will usually show a ‘cold nodule’, that is, the part of the thyroid gland that has been replaced by cancer does not concentrate the iodine and appears clear on the scan. However, cysts and some other lumps also show up as ‘cold nodules’. To make a diagnosis, the lump should be biopsied. This may sometimes be done by needle aspiration of fluid or cells from the lump, but the diagnosis is more certain if the lump is surgically excised and examined under a microscope. Frozen-section examination (see Section 2) may then allow the surgeon to proceed with further surgery immediately if the lump proves to be a cancer.
There are three main types of thyroid cancer.
The most common of the thyroid cancers (more than 60%) is the least malignant. This is called a papillary cancer and occurs three times more commonly in women than in men. This cancer often occurs in young people, occasionally teenagers or even children.
Papillary cancer may be present in different parts of the thyroid gland at the same time and may spread to nearby draining lymph nodes, but it usually does not spread further until very late in the disease. For this reason removal of the whole of the thyroid gland, together with any enlarged lymph nodes, will usually cure the patient. After total removal of the thyroid gland the patient must take thyroxine tablets by mouth.
The second most common type of thyroid cancer tends to affect adults of middle age and is called follicular cancer. It, too, usually presents as a lump in the thyroid gland and is usually not diagnosed with certainty until the lump has been removed surgically and examined under the microscope.
These cancers tend to be present in one lobe of the thyroid gland only and have a greater tendency to spread by the bloodstream to bone, lungs or liver rather than by lymphatics to lymph nodes. These cancers often more closely resemble normal thyroid tissue than do the other thyroid cancers, and although they usually appear as ‘cold nodules’ (areas of no function) in radio-iodine scans, they may sometimes scan as normal thyroid tissue or even rarely as hyperactive ‘hot nodules’ (areas with increased thyroid function).
Because of their tendency to involve one lobe of the thyroid gland only, they are usually treated by removal of the involved half of the thyroid gland, leaving the other half to carry out normal thyroid function and production of thyroxine.
Secondary cancers may be treated by surgical excision (if in lymph nodes), by radiotherapy or by radioactive iodine treatment. Chemotherapy is also sometimes used in the treatment of secondary cancers.
The third broad type of thyroid cancer is anaplastic cancer. As this is the most dangerous form of thyroid cancer, it is fortunate that it is also the least common. It tends to affect older people and may grow rapidly, presenting as an enlarging lump or enlarging swelling of the whole of the thyroid gland. It may press on the trachea (windpipe) and make breathing difficult. This cancer is virtually incurable by surgery and is best palliated by radiotherapy or sometimes chemotherapy.
The thyroid gland is occasionally the site of other primary malignant cancers, such as medullary cancer, lymphoma, sarcoma or even secondary cancers, but these are uncommon forms of thyroid malignancy.
CANCERS OF THE FEMALE SEXUAL ORGANS
Cancer of the uterus
There are two distinct types of cancer of the uterus: squamous-cell carcinoma (SCC) of the cervix (neck of uterus) and adenocarcinoma of the lining of the body of the uterus. SCC of the cervix is more common.
Cancer of the cervix
This cancer is most common in women who have had sexual activity with multiple partners starting early in life. Infection with a sexually transmitted virus, the human papilloma virus (HPV), is the major cause. It is also more common in women who have had several children, particularly if erosions and inflammation of the cervix resulted from the multiple pregnancies.
The earliest changes associated with this cancer are most frequently present in women between the ages of 30 and 40. Usually at this age there are no symptoms, but there may be a little blood-staining from the vagina between periods, especially after intercourse.
Cancers of the cervix tend to develop slowly but can usually be detected by routine cervical-screening examination (the Papanicolaou or cervical-smear test described in Section 2), in which abnormal (dysplastic) or frankly malignant cells may be found. A cervical-smear test is recommended at least every second year for all women or more frequently if there has been any suggestion of a special risk, to detect these cancers early and at a very curable stage.
Sometimes the cancers cannot be seen on visual examination of the cervix, but at other times a cancer may be seen as an eroded, reddish, ulcerated or possibly bleeding lesion. A biopsy is taken for pathological examination to confirm the diagnosis.
Very small early cancers may be treated by surgical removal of the cervix only, especially in women who wish to have more babies. Larger invasive cancers are best treated by removal of the uterus (total hysterectomy).
If cancer of the cervix is not diagnosed until it is more advanced, there is a risk that it may have spread to lymph nodes, especially the lymph nodes in the pelvis. This situation is more likely to be found in women of more than 40 years of age who have not had regular cervical-smear tests. These women often complain of some bleeding and discharge between periods. If an advanced, ulcerating or fungating cancer is present, it should be obvious on examination of the cervix. Surrounding tissues, such as the ureters (the tubes that pass urine from the kidneys to the bladder) or the rectum, may become involved, as well as the local draining lymph nodes in the pelvis. Such advanced cancers are usually treated by combination chemo/radiotherapy, possibly followed by surgery.
A truly major advance has been the development of a vaccine against HPV, which may eventually eradicate most cancers of the cervix in the way that smallpox and polio have been eradicated. Some people may experience a negative reaction, such as fainting, but this is also the case with many other vaccinations. In Australia it has become readily available at no cost for teenage girls and women up to 26 years of age, and is now also available for older women at their own expense.
Cancer of the body of the uterus (endometrial cancer)
Endometrial cancers tend to occur in older women, usually after menopause. It is believed that changes in female sex hormones, and especially an imbalance of hormones, may contribute to the development of these cancers.
The most common feature is post-menopausal bleeding and blood-stained discharge. The uterus is usually found to be enlarged. To make a diagnosis, the doctor performs a curettage and sends the specimens removed for microscopic examination.
Treatment of cancer of the body of the uterus is usually by complete removal of the uterus (total hysterectomy), with the removal of ovaries as well as lymph nodes in the pelvis. For advanced cancers radiotherapy is often given first as well.
As with most cancers, treatment at an early stage will allow good results, but for more advanced cancers the results of treatment are often disappointing.
If endometrial cancer has spread to other tissues or organs, it will often respond to hormone treatment (large-dose progesterone therapy), but a long-term cure is unlikely. Studies are being made of combined integrated treatment using chemotherapy first as ‘induction’ treatment, followed by radiotherapy and/or surgery (see Section 2).
Choriocarcinoma
Although a choriocarcinoma starts and grows in the uterus, it is not strictly a cancer of the uterus. A choriocarcinoma is best considered as a cancer of an abnormal pregnancy.
After conception an abnormal growth of tissue very occasionally develops instead of a normal foetus and placenta. If the foetus does not develop and the placenta grows as a group of cyst-like structures, something like a bunch of grapes, this is called a hydatidiform mole.
Sometimes the cells of a hydatidiform mole develop into an invasive cancer that is called a choriocarcinoma. Occasionally choriocarcinoma will develop in association with a foetus, usually abnormal, which is aborted spontaneously, or even with an otherwise normal pregnancy. However, most are in association with a hydatidiform mole, usually in women over 40 years of age.
In the past, choriocarcinoma spread widely and rapidly through the mother’s body and was a fatal form of cancer. Now the condition is treated by emptying the uterus of its contents (a curette) and giving combination chemotherapy. This is one of the success stories of modern chemotherapy, as choriocarcinoma was almost 100% fatal about 30 years ago but is now curable in 80% or more of cases.
Cancer of the ovary
The ovaries are the source of a greater variety of tumours, both benign and malignant, than any other organ. This is probably because of the nature of the ovaries as organs, with their function of undergoing monthly cyclic changes to produce eggs or ova for potential development into the new tissues of a foetus. They may also produce tumours that excrete hormones that may affect body development and function.
Cancers of the ovary may be solid, cystic or contain a mixture of solid and cystic elements. They tend to cause no symptoms early in their development, because they can easily grow to a large size in the pelvic/abdominal cavity without interfering with other structures, and so are often quite advanced when first diagnosed.
Symptoms and signs
When they have reached a certain size, cancers of the ovary usually cause a swelling in the pelvis and lower abdomen. The swelling may have been noticed by the patient or may be found on examination by a doctor. They may also sometimes cause local discomfort or pain. If they produce hormones, the first evidence may be due to hormonal changes such as premature cessation of menstruation and loss of feminine features, with a development of male characteristics such as growth of hair on the face or deepening of the voice. Sometimes generalised abdominal swelling may also be noticed, due either to a huge tumour or to fluid in the abdominal cavity (ascites).
Any rapidly enlarging swelling on an ovary, especially if it is solid or contains a mixture of cystic and solid elements, must be regarded with suspicion as likely to be malignant.
Investigations
A doctor will carry out an examination of the pelvis and pelvic structures by examining the lower abdomen, the vagina and rectum, but if this examination is not adequate the patient may be admitted to hospital for examination under a general anaesthetic.
Abdominal X-rays or CT scans may help, but ultrasound examination is usually the most helpful and the least harmful examination, especially in young women.
Laparoscopy or culdoscopy (see Section 2) may allow the surgeon or gynaecologist to see the contents of the pelvis, especially the ovaries.
Usually the diagnosis of cancer cannot be established with certainty until an operation (laparoscopy or laparotomy) has been carried out and a biopsy specimen of any suspicious lesion has been examined under the microscope.
Treatment
The best treatment of ovarian cancer is by the surgical removal of the ovaries. As the other ovary and sometimes other pelvic organs may also contain cancer, it is usual to remove both ovaries as well as the uterus and fallopian tubes and any other involved tissue. The operation may be followed by radiotherapy to the pelvis and abdomen. Often advanced tumours are removed as much as possible (cyto-reductive surgery) and the patient is then treated with a combination of chemotherapy drugs. This can frequently lead to a worthwhile remission. The drugs used are commonly of the platinum and taxol classes in combination.
Prevention
As cancers sometimes develop from benign tumours of the ovary and the ovaries have little function in post-menopausal women, it is usually advisable to remove both ovaries of women over 40 when treating a benign ovarian tumour. Gynaecologists also often advise removal of ovaries as a preventive measure when they perform hysterectomy (removal of the uterus) in women over the age of 40.
The ovaries are commonly a site for the development of secondary cancer from a primary cancer elsewhere. Cancer of the breast, stomach and bowel, and melanoma frequently spread to ovaries. These are removed if there is no apparent cancer anywhere else; otherwise treatment given will depend upon the best treatment for the type of cancer concerned and where it came from.
Cancer of the vulva
Like cancer of the anus, cancer of the vulva is a rather aggressive form of skin cancer, usually of the SCC type. Most occur in women of post-menopausal age. This cancer is often preceded by a long history of irritation or discomfort of the vulva, possibly with a local bloodstained discharge. There may be a pre-malignant condition of leukoplakia or a chronic rash. Previous infection with the sexually transmitted HPV may be responsible for some cases.
In the more advanced disease there may be an ulcer, a lump or a cauliflower-like growth. Spread to lymph nodes in one or both groins is likely to be present in about half of the patients.
Diagnosis is established by biopsy, and treatment is usually by wide and radical surgical excision, most often with satisfactory results, with most patients being cured. Pre-malignant conditions are also best treated by surgical excision to prevent cancer developing.
For very advanced cases radiotherapy offers palliative relief. Combination chemo/radiotherapy is used in some cases before or after surgery.
CANCER OF THE MALE SEXUAL ORGANS
Cancer of the testis
Testicular tumours are relatively rare, but when they do occur they are almost always malignant. Most occur in young adult males between the ages of 20 and 40.
There are no known causes of testicular cancer, apart from those cancers occurring in testes that have not descended into the scrotum from the abdomen at birth. If the testes are not present in the scrotum of infant boys, a surgical operation may be required to place the testes in their normal position. This may reduce the risk of development of testis cancer later in life, some time after puberty.
There are two main types of testicular cancer: seminoma and non-seminoma (also known as teratoma).
Seminoma is composed of a more or less uniform type of cell derived from the precursors of sperm cells.
Non-seminomas may have complex mixtures of pathological subtypes that are apparently more closely related to primitive pregnancy-like cells (e.g. yolk-sac, embryonal or choriocarcinoma types).
Symptoms and signs
Cancer of the testis is usually found as a painless and non-tender swelling of a testis. Only rarely is the swelling tender or painful. Occasionally swelling is not seen in the testis until there is evidence of the metastatic spread of the testicular cancer. These metastases may be noticed as a mass of enlarged and sometimes tender lymph nodes in the abdomen, enlarged lymph nodes in the neck (usually the left side) or as secondary cancers in lungs seen in a chest X-ray. Occasionally the first evidence of a testicular cancer may be the swelling of a man’s breasts due to changes in his hormones. In other patients the first evidence may be of general debility, anorexia (loss of appetite) and weight loss.
Investigations
If a swelling of a testis is likely to be cancer, investigations are carried out to look for evidence of secondary spread. CT scans, described in Section 2, may be helpful in detecting any enlarged lymph nodes in the abdomen and chest or involvement of the liver.
To confirm a diagnosis of cancer the operation of orchidectomy (removal of the testis) is carried out. The incision is carried out in the groin and the entire testis and cancer are removed from the scrotum. It is important also to have a blood sample sent to pathology for measurement of the tumour markers that are specific to testicular cancers, b-hCG and alpha-feto-protein. If these tumour markers are elevated, a fall in their levels after surgery can indicate that there is no metastatic spread and that the whole cancer has been successfully removed.
Treatment
Cancer of a testis is first treated by surgical removal of the testis.
For patients with seminoma and no evidence of spread after CT scans a simple course of radiotherapy to the draining lymph nodes in the abdomen is given as adjuvant treatment.
A careful follow-up watch is kept on patients with nonseminoma-type tumours and no evidence of spread detected in the follow-up blood tests and CT scans. However, even if the disease recurs or is widespread at diagnosis the vast majority of patients can be cured with combination chemotherapy. The drug cisplatinum is used, and it has been responsible for the dramatic improvement in outcome.
It is possible to subsequently lead a normal sex life and to father children with only one testis.
Cancer of the prostate
Cancer of the prostate is uncommon before the age of 50, but in Western societies it is the most common cancer in men over 65 and is increasing in incidence.
Its cause is unknown, but its association with old age is illustrated by the fact that more than 75% of men over the age of 90 have microscopic evidence of at least early prostate cancer. This cancer is less common in Asian countries. It is likely that the Western diet, high in animal products, plays a significant part in causing prostate cancer.
Recent studies have indicated that diets with a high content of legumes such as soybeans may be protective. These contain naturally occurring plant hormones (phytoestrogens) that may play a part in cancer prevention.
Symptoms and signs
The most common symptom of prostatic cancer is difficulty in passing urine. Non-malignant enlargement of the prostate (benign prostatic hypertrophy or BPH) is most often the cause of urinary difficulty, but prostate cancer is also a common cause, especially in older men.
Sometimes the first evidence of cancer of the prostate can be symptoms due to metastatic cancer either in the bone (causing pain or fractures) or in the liver. Secondary cancers in the lower vertebral column (back bone) or pelvis may cause pressure on a sciatic nerve that passes into the leg, causing severe pain in the back and leg called sciatica. Sciatica is more often caused by other conditions, but occasionally it is the first evidence of a cancer of the prostate.
Investigations
The prostate gland can be felt by a doctor in a PR (per rectal) examination. That is, a gloved finger is passed through the anus into the rectum and the prostate gland can be felt in front of the finger. Cancer in the prostate feels like a hard lump in the prostate, or sometimes the whole of the gland may feel hard and rigid.
CT studies will show the size and extent of the prostate, but ultrasound studies taken through the rectum will more precisely show any lumps or nodules in the prostate that may be a cancer. A biopsy may be taken with a needle on a spring-loaded gun directed into the prostate by ultrasound via the rectum.
X-rays will be taken for evidence of secondary spread into bones. These usually show up as sclerotic (dense white) areas in the bone. Chest X-rays may show evidence of secondary cancers in the lungs, in lymph nodes in the chest or even in the ribs. Isotope bone scans are also valuable in showing evidence of secondary bone cancer.
Blood studies may show evidence of anaemia due to secondary bone cancer destroying the blood-forming cells in bone marrow. Obstruction by the cancer of the flow of urine may cause infection in the bladder and possibly in the kidneys. The urine and blood are examined for evidence of infection in urine and for evidence of damage to the kidneys.
In recent years a blood test, the prostate specific antigen (PSA) screening test, has been developed to indicate whether there is likely to be an abnormality in the prostate. This is a special immunological test that is now commonly used in men over the age of 50 to help find those with early prostate cancer who might be effectively treated by operation. A raised PSA level does not necessarily indicate that cancer is present, but it does indicate the need for further investigations, possibly including ultrasound study and biopsies. It may be highly elevated in men with metastatic spread to bone.
Treatment and treatment controversies
There is considerable controversy in regard to both the value of screening tests and the actual treatment of prostate cancer. The PSA screening test has led to the diagnosis of prostate cancer in increasing numbers of middle-aged and elderly males. Yet even if a biopsy diagnosis of cancer is confirmed, it is estimated that only about one in four of those cancers will grow in a malignant fashion and spread to tissues beyond the prostate in such a way that it is likely to cause the patient’s death. There is as yet no definite way of identifying those cancers that are likely to spread. Most prostate cancers are slow growing and even after many years may show no evidence of spread, but some will spread to such places as lungs, liver and especially to bones, where they are likely to form painful secondaries and lead to the death of the patient.
Appropriate treatment of early prostate cancer will cure most patients, but all treatments have serious side effects, and it is not entirely possible at this stage to determine which patients will benefit from treatment and who might just as well be left without treatment.
The most distressing treatment side effect is impotence. This occurs in 50% or more of patients, whether treated by total prostatectomy (surgical removal of the whole prostate gland) or by radiotherapy. Treatments available at present are often effective for impotence resulting from prostatectomy, but when hormone treatment is used to treat metastatic disease, either by giving anti-testosterone medication or by orchidectomy (castration) or both, impotence is virtually inevitable.
Although controversial, the following are standard treatments that should be considered and discussed between a patient and his medical advisors.
For small cancers apparently confined to the prostate, total surgical removal of the prostate gland, and if necessary with removal of adjacent lymph nodes, should result in cure. This may be the best treatment for men who are reasonably young and fit with an otherwise long life expectancy.
Alternatively, obstruction to the flow of urine may be relieved by a TUR (trans-urethral resection), in which an instrument (resectoscope) is passed into the urethra through the penis and some of the enlarged prostate is cut away to relieve obstruction. Specimens of the tissue are sent for microscopic examination.
Cancer of the prostate will often respond to radiotherapy, which is often used to treat both primary prostate cancer and a limited number of painful secondary deposits in bone. If radiotherapy is used to treat the primary cancer, it can be given as a conventional external beam or as radioactive pellets actually inserted into the prostate. This is called brachytherapy. Modern techniques of brachytherapy can now produce equally good results to surgery.
The male hormone testosterone stimulates prostate cancer, so anti-testosterone treatment is also used, especially for more widespread cancer. Patients with metastatic prostate cancer are often given effective palliative relief by treatment with such drugs. The drugs used either antagonise the action of testosterone or inhibit its synthesis. An alternative treatment likely to give similar response is to remove the source of male hormones, the testes (bilateral orchidectomy).
Prostate cancer will respond to treatment with some cytotoxic agents, but these are normally only used in patients whose advanced cancer no longer responds to hormone management. Excellent improvements in quality of life can be obtained when relatively non-toxic forms of chemotherapy are used, often in combination with cortisone-like drugs such as prednisone.
CANCERS OF THE BLADDER AND KIDNEYS
Bladder cancer
Although rare today, more than a century ago bladder cancer was found to be increased in industrial workers exposed to aniline dyes and rubber manufacturing.
Smokers have about a threefold increased risk of contracting bladder cancer. It is also more common in the Nile valley in Egypt, where parasitic diseases (schistosomiasis) infecting the bladder start an inflammatory process that can develop into malignancy. Cancer may also develop in a benign cauliflower-like tumour of the bladder known as a papilloma. Some patients have several small papillomas in the bladder wall, and any one of these can change to a cancer if not treated.
The most common symptom of bladder cancer is blood in the urine (haematuria). The blood may be intermittent at first but becomes more constant as the cancer grows and invades the bladder wall. At a later stage there may be discomfort in passing urine (dysuria) and symptoms of bladder infection (cystitis), increased frequency of passing urine, and burning and pain. Sometimes a ureter (the tube through which urine passes from the kidney to the bladder) may become obstructed by the growth and may cause pain in the loins due to back pressure on the kidney.
After losing blood in the urine for some time, anaemia may develop and symptoms of anaemia (pallor, tiredness, palpitations, etc.) may be noticed.
Investigations
The urine is examined for blood and may also be examined for cancer cells. Excretory urograms (IVP X-rays, described in Section 2) may show a filling defect or lump in the bladder. They may also show evidence of obstruction to a ureter if this is present. A CT scan may reveal a lump in the bladder wall.
The critical investigation, however, is cystoscopy. The flexible fibre-optic cystoscope (discussed in Section 2) is passed into the bladder through the urethra (the tube for passage of urine from the bladder), usually under general anaesthesia. The inside of the bladder is then examined by the doctor. A small piece of any suspected cancer together with a small piece of adjacent bladder wall is taken as a biopsy for microscopic examination.
Types of bladder cancer (pathology)
There are various degrees of bladder tumours, ranging from a single benign cauliflower-like papilloma to an invasive, rigid, ulcerated and thickened cancer. Between these extremes there may be several papillomata (small warts or cauliflower-like growths), one or more of which may show signs of early malignancy, or there may be a malignant lump in the bladder wall. Bladder cancers tend to remain confined to the bladder wall for a long time before they spread. After a time, however, bladder cancers may involve the whole thickness of the bladder wall and even invade the rectum or other organs nearby in the pelvis. They may also spread to nearby lymph nodes and subsequently to lungs and other organs.
Treatment
Small papillomata of the bladder are usually treated by burning them off with an instrument called an electro-cautery, which is used through a cystoscope, or simply resected. The patient is cystoscoped regularly afterwards in case the tumour recurs.
For larger papillomas or early invasive cancers treatment by radiotherapy or surgical excision, or a combination of both radiotherapy and surgical excision, may offer good prospects of cure. Subsequent instillation of a modified bacteria (BCG) into the bladder can induce an immune response retarding tumour regrowth.
For more advanced cancers it may be necessary to operate to remove the whole of the bladder (total cystectomy). A new type of bladder is then usually made by the surgeon from a part of the bowel.
When cure by surgery is not possible, palliative radiotherapy may give relief. Chemotherapy has a limited place in the treatment of bladder cancer but can offer palliation in some patients with metastatic cancer.
Cancers of the kidney
Kidney cancers are not common, but there are three well-recognised types. The Wilms’ tumour or nephroblastoma occurs in children. In adults kidney cancers are either the adenocarcinoma (sometimes called hypernephroma or Grawitz tumour) or carcinoma of the renal pelvis.
Wilms’ tumour (nephroblastoma)
Wilms’ tumour is usually found in children of less than four years of age and can even be present at birth. Although in most cases only one kidney is affected, occasionally it is bilateral (i.e. present in both kidneys). This cancer is most commonly found as a lump in the loin of an infant. It may cause the child to be in general poor health, with a fever, anaemia or sometimes blood in the urine. It may spread to nearby lymph nodes or into the large veins. From these veins cancer cells may be carried by the blood to the lungs, where secondary growths may develop.
Adenocarcinoma (Grawitz tumour or hypernephroma)
This is the most common type of kidney cancer and is usually seen in adults of middle age or older. The first symptom is usually the passage of blood in the urine, most often not associated with pain. (Passing of blood in the urine with pain in the loin is more likely to be caused by a kidney stone.) There may be a fever, or a lump may be felt in the loin, or sometimes there is localised pain. This cancer may spread into nearby lymph nodes but commonly grows into the large renal vein (the vein taking blood from the kidney) and may spread by the bloodstream into the lungs, liver or bones. Sometimes the first evidence of this cancer is the presence of secondary cancers in a lung or in one or more bones.
Adult smokers have a twofold to threefold increase in the incidence of kidney cancers.
Carcinoma of the renal pelvis
Carcinoma of the renal pelvis is rather like cancer of the bladder and behaves in a similar manner. The first sign is usually blood in the urine. This cancer sometimes develops as a reaction to a stone present in the kidney for a long time.
Investigations for kidney cancers
X-rays of the abdomen may show an enlarged kidney. Excretory urograms (IVP), CT scans, ultrasound and arteriography (see Section 2) are all useful investigations to help diagnose a tumour in a kidney. They will also help determine whether a kidney lump is solid and likely to be cancer or a fluid-filled cyst and probably not malignant.
Other investigations include examination of the urine for blood or malignant cells and X-rays of the lungs for evidence of secondary cancer. If there is evidence of swelling or painful areas in bones, these will be X-rayed and bone scans may be arranged to look for evidence of secondary bone cancers.
Treatment
Cancer of a kidney is best treated by surgical operation to remove the kidney (nephrectomy).
For Wilms’ tumour (nephroblastoma) in children results are much better if radiotherapy and chemotherapy are used in combination with surgical removal of the kidney.
For adenocarcinoma surgical treatment (removal of the kidney) is the only likely cure for a patient. Radiotherapy and chemotherapy may be used as palliative treatment in advanced cases, but results have been disappointing. Sometimes these cancers will show a temporary response to male or female hormones. Adenocarcinoma of the kidney can sometimes spread to a lung as a single secondary, and this can sometimes be cured by an operation removing the part of the lung containing the metastasis. Similarly, patients who have only a few slow-growing metastases can have very long-lasting positive responses to intensive radiotherapy.
For cancer of the renal pelvis best results are achieved if the kidney is removed together with the whole of the ureter and a small part of the bladder as small seedlings of this cancer sometimes grow in the ureter between the kidney and the bladder. The new generations of small-molecule signal-inhibiting targeted drugs, such as Glivec, which is especially effective in treating chronic myeloid leukaemia, are showing encouraging results in clinical trials, but as yet they are not generally available.
CANCERS OF THE BRAIN
Although most brain cancers occur in people over the age of 45 with a peak incidence between 60 and 70, the brain is also one of the more common sites for primary cancer in children and young adults.
There are two groups of cells in the brain that may form tumours: the glial cells (or true brain cells), from which most of the malignant tumours (cancers) develop; and the non-glial cells or supporting cells (such as cells of the meninges covering the brain or cells of the sheaths surrounding nerves), from which develop the majority of non-malignant (benign) tumours.
Cancers that arise from true brain cells or glial cells are called gliomas. There are a number of different types of gliomas, which range from the more slow-growing types called astrocytoma or oligodendroglioma to more rapid and highly malignant types called medulloblastoma or glioblastoma multiforme. These different types of glioma tend to occur in different parts of the brain in children and adults. They also have other differences: the medulloblastomas (more commonly seen in young people) are usually highly radio-sensitive and are sometimes cured by radiotherapy, but other types are less radio-sensitive, if at all.
Symptoms and signs
Brain cancers tend to cause two types of clinical features:
The common general features of cancer in the brain are due to pressure on and swelling of the brain as a whole. This causes headaches, nausea, vomiting and disturbances of vision due to papilloedema (swelling of the optic nerve at the back of the eye). Other features may include listlessness, tiredness and personality change. The sufferer may progressively withdraw from social contact and gradually become confused and stuporous, and may lapse into coma. In young children the increased pressure may cause the head to enlarge, and hydrocephalus (so-called ‘water on the brain’) may develop.
It should be noted that in children, convulsions or fitting are most often caused by a fever or other less serious problems. Fitting alone is rarely caused by cancer in children. In an adult with no previous history of epilepsy, injury or fitting from another known cause, however, the sudden onset of a fitting attack may be the first sign of a brain tumour.
Focal features are due to the cancer’s interference with the function of a local region of brain. These features will depend upon the site of the tumour. In one place it may be interference with speech, in another it may be loss of movement of an arm or leg and in another it may be loss of feeling or sensation of a part of the body. Tumours in other places may cause local twitching or focal fitting with different sensations, such as sensation of smell or visual hallucinations like the flickering of lights. In other areas tumours may cause disorders of balance, clumsy movement or interference with cranial nerves (the nerves that leave the brain), such as the optic nerves for vision, the nerves that move the eyeball or the facial nerves that move the muscles of the side of the face.
Investigations
The CT and MRI scans have revolutionised investigations for brain tumours. Before these scans were invented, cerebral arteriography (X-rays of arteries supplying the brain), radio-isotope scans and air encephalograms (see Section 2) were used almost routinely, together with a number of other investigations such as the EEG (electroencephalogram), which records brainwave activity. Nowadays, however, the MRI scan in particular usually supplies most of the information that could be obtained by these older investigations and even more precisely. Angiography may still give added information, particularly concerning the accumulation of new blood vessels in the cancer that supply it with blood.
Treatment
Most benign cerebral tumours can be cured by surgical removal, but malignant tumours (brain cancers) are not often curable. For this reason it is vital to determine – usually at operation – whether a tumour in the brain is benign or malignant (cancer). If malignant, it is also important to determine the type of malignancy, as the outlook for some types is better than others and some (such as medulloblastomas) may be curable.
Although most true brain cancers (gliomas) are not curable, most patients can be given considerable relief of symptoms by a number of means. First, certain drugs (corticosteroids) can be used to reduce pressure on the brain and so relieve headaches and other pressure symptoms. Then surgical operation can be carried out to remove most of the cancer, giving further and more prolonged relief of symptoms. Following surgery the use of radiotherapy alone will usually further improve the outlook for a period.
Recent studies have shown that the use of post-operative chemotherapy with radiotherapy has given added benefit, and some apparent cures have been reported, particularly in the case of medulloblastomas.
THE LEUKAEMIAS AND LYMPHOMAS
The leukaemias
Leukaemia is a malignant growth or cancer of blood-forming cells. Leukaemias are divided into two general types according to the kind of blood-forming cell that has become malignant: the lymphoid and myeloid leukaemias.
In lymphoid leukaemia the cells that have become malignant are the bone-marrow cells that normally make the white blood cells called lymphocytes. Lymph nodes and lymphoid tissue are usually involved and become enlarged. In myeloid leukaemia the cells in the bone marrow that normally make the other types of white blood cells (e.g. polymorphs or neutrophils) have become malignant. The spleen usually becomes involved and enlarged.
Leukaemias may be acute or chronic according to whether the disease would tend to run a rapid and fatal course (acute leukaemia) or progress more slowly (chronic leukaemia). The acuteness or chronicity is determined by the maturity of the cell types involved. Thus there are four main types of leukaemia:
It is important to distinguish between the major types of leukaemia as they have quite distinct outlooks and respond differently to different drugs.
Leukaemia occurs throughout the world, but the incidence varies in different countries and in different races. All types of leukaemia are slightly more common in males. The Scandinavian countries and Israel have the highest incidence of leukaemia, and the lowest incidence is in Chile and Japan. In the USA the highest incidence is in Jews and the lowest is in African Americans.
The overall incidence of acute lymphocytic and acute myeloid leukaemia is about equal, but there is a distinct age difference. Acute leukaemia accounts for about half of all cancers in children, and acute lymphocytic leukaemia is the most common of all cancers in young children, with a peak incidence between the ages of two and four. The incidence of acute myeloid leukaemia increases with age.
The causes of leukaemia are not known, although some predisposing factors are recognised. The myeloid leukaemias have been linked with ionising radiation, and there is evidence that exposure of a foetus to X-rays during pregnancy is associated with a slightly increased risk of leukaemia developing later in childhood. However, there is no evidence that the normal use of diagnostic X-rays in adults is associated with leukaemia.
Excessive exposure to some chemical agents such as benzene is associated with a slightly increased risk of leukaemia. Acute myeloid leukaemia will also develop a little more often in patients who have had some other form of cancer, including Hodgkin lymphoma or cancer of the ovary.
The use of anti-cancer cytotoxic drugs, and especially the use of these drugs with radiotherapy, also slightly increases the risk of later development of leukaemia.
Familial leukaemia is rare, although some families with multiple cases of leukaemia have been reported. In general the siblings of a child with leukaemia have only a slightly higher risk of developing leukaemia, although if one identical twin develops acute leukaemia the other twin has roughly a 20% chance of developing the disease as well.
People with Down’s syndrome have a 20 times greater risk of developing acute leukaemia than other people. Mothers of advancing age not only have an increased risk of having children with Down’s syndrome, but their non-Down’s children also have a slightly greater risk of developing acute leukaemia.
Viruses are known to cause leukaemia in some animal species, but there is no evidence that this is the case in humans.
The acute leukaemias
Symptoms and signs
The symptoms of acute leukaemia are due to replacement of the normal blood-forming cells of bone marrow by malignant leukaemic cells and infiltration (invasion) of other tissues such as the spleen, lymph nodes, tonsils and sometimes the liver, kidneys, lungs and brain.
Fever, weakness, anorexia (loss of appetite), pallor and infection are common. Infection is especially common in the region of the tonsils or anus, and the lungs may also become infected, causing pneumonia. Sometimes there is pain in bones or joints. The lymph nodes, tonsils and spleen are commonly enlarged, and sometimes the liver and kidneys are enlarged.
There may be signs of bleeding from any site but especially from the gums, the digestive tract or anus. Bleeding in the brain or from the lungs may also occur. Thromboses (clots) may also develop in veins.
Meningitis due to leukaemic cell spread into the meninges (the membranes covering the brain) frequently occurs in patients with acute lymphatic leukaemia unless it is prevented by radiotherapy or chemotherapy.
Investigations
The diagnosis of leukaemia can only be made after careful examination of blood and bone marrow. Blood is taken by a needle from a vein in the arm, and bone marrow is usually taken with a small instrument that is used to puncture a bone of the pelvis (the iliac crest). Bone-marrow biopsy is done with sedation and local anaesthesia. A pathologist then examines the blood and bone marrow for leukaemic cells and for other features of leukaemia. These may include anaemia (with a reduction in numbers of red blood cells); a reduction in the number of normal white blood cells, with an increase in abnormal white cells; and a reduction in the number of platelets (the particles that help blood-clotting).
Patients with acute myeloid leukaemia are usually found to have various abnormalities of chromosomes. Analysis of these may allow some prediction of the outcome of therapy. There may also be changes in blood chemistry, such as increased uric acid (which may be associated with features of acute gout).
Treatment
Encouraging progress has been made in recent years in treatment of the acute leukaemias.
The best opportunity to achieve the maximum cure of leukaemia is when the disease is first diagnosed, as cells that remain after the first treatment tend to develop resistance to drugs. It is therefore important that patients with acute leukaemia be immediately referred for specialist care so that the most effective treatment can be given under expert supervision from the beginning.
Chemotherapy using cytotoxic drugs and cortisone forms the basis of modern treatment. Combinations of effective cytotoxic drugs have produced the best results.
Anti-cancer drugs do not pass in high concentration into the brain. Because after a time most acute lymphatic leukaemic patients will develop the disease in the brain, injections of cytotoxic drugs are given into the meningeal space around the brain. In the case of acute myeloid leukaemia, brain involvement does not occur so often, but this treatment is given immediately if there is any sign that there may be brain or central-nervous-system involvement.
With the best current treatment methods, over 90% of children and about 80% of adults with acute lymphatic leukaemia now achieve complete remission (that is, the disease apparently disappears and the patient feels and looks well again).
With acute myeloid leukaemia good results from chemotherapy have not been as reliable. Recently, in attempts to further improve results, bone-marrow transplantation has been used effectively, especially in people aged under 40. In marrow transplantation the leukaemic cells are destroyed by big doses of chemotherapy and radiotherapy (total body irradiation). This is a dangerous procedure and is only carried out in highly expert departments. The patient is then given injections of bone marrow taken from a matched donor (with similar body cells unlikely to cause a rejection reaction). The best donor is usually a parent or a sibling. More recently bone-marrow cells can be collected from the blood after injection of a bone-marrow-stimulating hormone. This is called granulocyte colony-stimulating factor (G CSF).
Bone-marrow transplantation involves a number of risks and problems and can only be carried out by appropriately trained experts in specially equipped hospitals, but the results have been most encouraging in this otherwise fatal illness. A further encouraging development is quite new at the time of writing: when a well-matching bone-marrow donor is not available, umbilical-cord blood has been used as an alternative, with good results in children and in some adults.
In recent years treatment with immunotherapy has been further investigated. Although major success has not as yet been achieved, there have been some interesting results that give hope for better treatments becoming available in the future.
During the acute illness there may be special problems of anaemia, lowered resistance to infection, bleeding or even clotting. These may require blood transfusion or platelet transfusion and antibiotics. Aspirin should be strictly avoided as it interferes with blood-clotting.
Chronic myeloid (granulocytic) leukaemia
Chronic myeloid leukaemia can occur at any age, but its highest incidence is between the ages of 30 and 50. Although there is no known cause in most cases, it was found that in Japan five to eight years after the atomic-bomb explosions there was an increase in both acute and chronic myeloid leukaemia.
In chronic myeloid leukaemia there is a great increase in the number of white cells in the blood. This is associated with an increase in the number of cells in bone marrow. There may also be a considerable increase in the numbers of blood platelets (the particles in blood responsible for clotting). The disease is due to a very specific chromosomal abnormality that results in a mutant form of an enzyme called a signal enzyme (tyrosinekinase) that continuously drives cell division.
Symptoms and signs
One of the more common symptoms of chronic myeloid leukaemia is pain in the left upper abdomen due to an enlarged spleen. The spleen is usually easily felt in patients with this disease (a normal spleen cannot be felt with examining fingers). There may also be features of anaemia, tiredness, weight loss or fever. Sometimes, abnormal bruising, bleeding or clotting problems may be the first evidence of the disease.
Investigations
Blood count and a bone-marrow biopsy will usually establish the diagnosis.
Treatment
There are two phases of chronic myeloid leukaemia. The chronic phase is the least dangerous and with modern treatment may last for many months or years before the dangerous acute phase takes over.
During the chronic phase the disease can now be kept under good control and possibly cured in some individuals with the drug Glivec. This is a drug form of the enzyme (called a small-molecule inhibitor) that promotes cancer-cell division (mutated tyrosine-kinase enzyme). The drug is given by mouth and turns off the signal for cell division. With this treatment the blood count returns to normal and the spleen is no longer enlarged. The patient’s response can be monitored by tests searching for the presence of the abnormal chromosome. This test (called a polymerase chain-reaction (PCR) test is looking for minute quantities of the abnormal DNA or genetic material responsible for the cancer-cell change.
An alternative treatment for younger patients who have a compatible donor is bone-marrow transplantation. This can cure some 60–70% of patients. However, it has severe side effects and requires several weeks in hospital.
In some patients a more acute and more dangerous form of this disease will develop, resembling acute myeloid leukaemia. This phase of the disease is more difficult to control. Cytotoxic chemotherapy with cortisone might give control for a period.
Chronic lymphocytic leukaemia
Chronic lymphocytic leukaemia tends to occur in older people of an average age of 60. In this disease there is an overproduction of mature and relatively normal-looking lymphocytes, with increased numbers of lymphocytes in the blood. (Lymphocytes are one of the main types of white cells in the blood. They are in high concentration in lymph nodes and some other tissues.)
Symptoms and signs
The most obvious feature of this cancer is lymph-node enlargement. Enlarged lymph nodes may be felt as lumps in the sides of the neck or in the armpits (axillae) or groins. Enlarged lymph nodes in the abdomen are more difficult to feel, but enlarged lymph nodes in the chest may be detected on a chest X-ray. The spleen and liver may also sometimes be enlarged. The normal bone marrow may be replaced by malignant lymphocytes, and the patient may become anaemic (deficient in red cells) and deficient in the circulating clotting particles called platelets. This may lead to bleeding and clotting problems. Due to the replacement of normal white cells by abnormal white cells, the patient has a decreased ability to combat infection and may also have immunologic abnormalities. Currently the majority of patients are actually diagnosed when asymptomatic (having no symptoms) after a blood count for some other reason. This asymptomatic state may last for many years.
Investigations
Blood count, a bone-marrow biopsy and special immune tests (tests of cell surface markers on the abnormal lymphocytes) will establish the diagnosis.
Treatment
Chronic lymphocytic leukaemia is usually a very slowly progressing disease, and many patients may not need treatment for many years. There is no evidence that the disease can be cured by early treatment, and treatment is usually reserved for episodes of the disease that are causing the patient to feel ill or causing other problems.
Large and conspicuous lymph nodes and a large spleen can be reduced by radiotherapy. If the patient’s general health is poor, treatment with anti-cancer cytotoxic drugs, often with cortisone, will usually cause reduction of enlarged lymph nodes and spleen and improve the bone marrow, and will make the patient feel better. Two cytotoxic anti-cancer drugs are commonly used: chlorambucil and cyclophosphamide. Both are given by mouth. Newer active drugs include the antimetabolite fludarabine and the monoclonal antibody Mabthera.
Unlike chronic myeloid leukaemia, chronic lymphatic leukaemia does not degenerate into an acute type of leukaemia. However, it may occasionally change into a lymphoma-like disease, as described below.
The lymphomas
The lymphomas are a group of malignant diseases (cancers) of the tissues that constitute the body-defence system called the reticuloendothelial or immune system. That is, the lymphomas arise in lymph nodes or in lymphoid tissue elsewhere, such as the tonsils, the spleen, the wall of the stomach or bowel, the liver, lung, kidneys or skin.
There are two main types of lymphoma: Hodgkin lymphoma (previously called Hodgkin’s disease) and the so-called non-Hodgkin lymphomas (NHL).
Currently about 12% of cases are Hodgkin lymphoma. The incidence of this disease has remained stable, while that of non-Hodgkin lymphoma has progressively increased over recent decades. The reasons for this are not clear.
Lymphomas are the sixth most common cause of death from cancer in Australia and commonly occur in young people. The average age is about 30 for Hodgkin lymphoma and a little over 40 for non-Hodgkin lymphoma.
The causes of most lymphomas are not known. Viruses are known to be a cause of lymphomas in some animals but, with one exception, they have not been found to be a significant cause of lymphoma in humans. A lymphoma called Burkitt’s lymphoma, which is uncommon in most countries but is common in children in tropical Africa and New Guinea, has been found to be associated with infection by the Epstein-Barr virus. This same virus causes glandular fever, and it has been found that in Western societies people who have suffered from glandular fever have a slightly increased risk of developing a lymphoma later in life. On the other hand, doctors and nurses who specialise in caring for people with lymphoma have not been found to have any increased risk of developing the disease.
It is well recognised that people with a deficiency of the immune system, especially AIDS patients, but also others (such as people who have had a kidney transplant and are given drugs to suppress the rejection of the transplanted kidney), have an increased risk of developing a lymphoma. There is also a slightly increased tendency to develop lymphomas in some families, but this may be due to a hereditary tendency towards immune deficiency.
Hodgkin lymphoma
Symptoms and signs
The most common sign of this disease, especially in young people, is enlarged lymph nodes, usually in one side of the neck. The nodes are rubbery and movable and usually feel distinctly different to the hard enlarged nodes that may result from secondary spread from other cancers.
Sometimes other symptoms are present: malaise (a general feeling of ill health), fever or weight loss. Occasionally pain in swollen lymph nodes following drinking alcohol is a feature.
The disease usually progresses from the site of origin (most commonly lymph nodes in the neck) to other lymph nodes nearby, then to lymph nodes in the chest or abdomen, to the spleen, and eventually to the liver and bone marrow. The earlier the disease is detected before it has spread widely, the greater the likelihood of cure by modern treatment.
Investigations
In order to decide on the best treatment for a patient it is important to find out as accurately as possible which lymph nodes and which organs are involved with this form of cancer. If this disease is suspected, the doctor performs a thorough examination of the patient, including all lymph-node areas, spleen, liver and chest. CT scans of the chest and abdomen can reveal enlarged lymph nodes, and this is complemented by PET scanning if it is available. Blood counts are also done, including tests relating to malignancy, such as the erythrocyte sedimentation reaction (ESR) and serum lactate dehydrogenase (serum LDH) tests.
The doctor then makes sure of the diagnosis by having the most obvious and easily removed lymph node excised by a surgeon and examined under a microscope. Any patient who has a non-tender lymph node greater than 2–3 cm in diameter remaining enlarged for more than four to six weeks without an obvious cause should have that node removed and examined. This will allow diagnosis or exclusion of lymphomas or other serious disease. In Asia or Africa tuberculosis sometimes mimics all the clinical features of lymphoma. Examination of excised lymph nodes will distinguish the diseases. A bone-marrow biopsy may be done in certain patients.
Treatment
Previously patients with Hodgkin lymphoma had an abdominal operation to determine how advanced the lymphoma was and what tissues were diseased. That operation involved removing some lymph nodes and often the spleen, and possibly a biopsy of the liver, all to be examined microscopically. It is now virtually never performed, due to the accuracy of CT and PET scanning.
Treatment of Hodgkin lymphoma depends on the stage of the disease and includes chemo/radiotherapy or chemotherapy alone. Treatment must be given by experts experienced in treating this disease, usually in multidisciplinary teams in specialised centres. It is now possible to cure the majority of patients.
In general limited areas of disease are best treated by an initial course of combination chemotherapy followed by radiotherapy to the areas of original disease. Modern linear accelerators are the most appropriate equipment for radiation therapy. The exact doses, techniques of delivery and field of irradiation are planned using sophisticated computer technology.
For more widespread disease treatment usually involves more extensive courses of combination chemotherapy. Again, to achieve best results and to keep toxicity to a minimum (see Section 2), treatment should be given by experts who are familiar with the use of these drugs and experienced in treating lymphomas. There have been considerable improvements in the chemotherapies available, with a reduction in immediate and long-term toxicity.
Non-Hodgkin lymphoma (NHL)
Like Hodgkin lymphoma, this group of diseases begins in reticuloendothelial or lymphatic tissues (the immune defence system) and is most commonly found in lymph nodes. However, the first indication of NHL may be the enlargement of, or lumps in, the spleen, tonsils or other organs such as the stomach, bowel, lung, bone or skin.
Non-Hodgkin lymphoma is not just one disease but a complex and wide range of diseases. The particular type of lymphoma depends upon the predominant type of malignant cells involved and their behaviour. The key issue is the type of lymphoma. They usually fall into three main classes according to their clinical behaviour or level of aggressiveness: low-grade, intermediate and high-grade forms.
Investigations
Diagnosis is usually made by surgical removal of an enlarged lymph node or biopsy of a lump in another tissue with microscopic examination.
Non-Hodgkin lymphomas tend to behave according to the predominant type of malignant cell. As with Hodgkin lymphoma, operations involving the removal and examination of potentially affected tissues are rarely needed. In the non-Hodgkin lymphomas the disease tends to involve a number of tissues other than lymph nodes, and the best form of treatment will depend upon the predominant type of malignant cell rather than the types of tissue involved. However, investigations similar to those for Hodgkin lymphoma are usually required. These include full blood count, CT scan of chest and abdomen, bone-marrow biopsy, liver biopsy and, increasingly, PET scans as they become more widely available (see Section 2).
Treatment
Just as for Hodgkin lymphoma, treatment of the non-Hodgkin lymphomas is by radiotherapy, chemotherapy or both. However, depending on the type of lymphoma, different plans of radiotherapy or different programs of chemotherapy are used. It is therefore essential that the patient be treated by a team of experts who can best determine the type and extent of disease and arrange the most appropriate plan of treatment.
In general, radiotherapy is best used for localised disease. With the non-Hodgkin lymphomas, however, there is a considerable risk that the disease is present in more than one site or in more than one tissue, and treatment by general body chemotherapy (systemic chemotherapy) is usually required. Sometimes the use of one cytotoxic agent only will achieve good results, but in general the best results are achieved when a combination of two or more cytotoxic drugs is used.
Over recent years the results of treatment of most non-Hodgkin lymphomas have improved significantly with modern treatment regimens. This is especially the case for some specific types of lymphoma. For some younger patients, even with advanced disease, very-high-dose toxic treatment followed by a bone-marrow transplant may be used with a good chance of success. A major improvement in treatment outcome has been the result of the development of a genetically engineered antibody directed against the lymphoma cells. This is produced using biotechnology industrial processes using mouse cells to produce a humanised antibody. The antibody is named Mabthera (ritiximab) and is used in combination with chemotherapy. The results of treatment for some of the early-stage lymphomas can be excellent, with a high cure rate, particularly for the so-called diffuse large B cell lymphomas.
SOFT-TISSUE SARCOMAS
The soft tissues are those that surround the bones of the body. They include muscles, fat, fascia, nerves, tendons, blood vessels and lymphatic vessels. A malignant tumour of one of these tissues is a ‘sarcoma’. However, the general term ‘cancer’ is often used to include sarcomas as they are a malignancy in many ways similar to cancer.
The majority of soft-tissue tumours are not malignant; it is only when they are malignant that the term sarcoma applies. Most tumours of fatty tissue are lipomas; when one of these is malignant, it is called a liposarcoma. Similarly, most tumours of fibrous tissue are benign and are called fibromas, and most tumours of nerves are benign and are called neuromas. Most blood-and lymph-vessel tumours are benign and are called angiomas.
Thus, sarcomas are classified according to the type of tissue from which they arise and the type of tissue they most resemble. A fibrosarcoma is a malignant tumour or cancer of fibrous tissue; a liposarcoma is a malignant tumour or cancer of fatty tissue; a neurofibrosarcoma is a malignant tumour or cancer of nerve tissue; a malignant fibrous histiocytoma (MFH) is a sarcoma of histiocytes (the protective cells most often found in soft tissues); and a synovial sarcoma is a malignant tumour of the synovial membrane that lines joints and tendon sheaths.
A myosarcoma is a malignant tumour of muscle. Myosarcomas may be further classified as rhabdomyosarcoma or leiomyosarcoma. A rhabdomyosarcoma is a malignant tumour of a voluntary muscle (that is, one of the muscles of the body over which we have movement control, such as those in our arms, legs, abdomen, back, head and neck, and the muscles used in breathing). A leiomyosarcoma is a malignant tumour of involuntary muscle (that is, one of the muscles over which we have no conscious control, such as the muscle in the wall of the stomach or bowel, and the muscles in the wall of the uterus or the wall of large blood vessels).
An angiosarcoma is a malignant tumour of blood or lymph vessels. In the case of blood vessels it is called a haemangiosarcoma, or in the case of lymphatic vessels it is called lymphangiosarcoma.
Soft-tissue sarcomas occur in people of all ages from birth to old age, but they are much less common than true cancers. Soft-tissue sarcomas make up only about 2% of malignant tumours.
In general sarcomas have a tendency to recur locally after surgical excision and also to spread. While most cancers tend to spread via the lymph vessels to lymph nodes before they spread to lungs or other body organs, most sarcomas tend to spread via blood vessels to lungs rather than to lymph nodes.
Classification-pathological types
Fibrosarcoma
Fibrosarcomas develop in the fascia or fibrous tissue that covers and surrounds muscles, nerves and other tissues and is distributed widely throughout the body. Thus a fibrosarcoma may develop almost anywhere in the body, especially in a limb or in the tissues of the trunk. One very fibrous and slow-growing type of fibrosarcoma, called a desmoid tumour, has a tendency to grow into nearby tissues and to recur locally after surgical excision but rarely spreads to other organs. Other more cellular and less fibrous types have a greater tendency to spread.
Liposarcoma
These tumours develop from fatty tissue and may arise anywhere in the body where fat is present. They tend to vary from a low-grade malignancy likely to recur locally after removal but unlikely to spread to a high-grade malignancy in which both local recurrence and secondary spread to lungs is common.
Rhabdomyosarcoma
This malignant tumour presents as a swelling in voluntary muscle, especially in muscles in the limbs, and is the sarcoma most likely to spread to lymph nodes.
Leiomyosarcoma
This malignant tumour may occur at any site where there is smooth muscle, including the wall of the stomach, bowel or uterus, or the wall of large blood vessels.
Neurofibrosarcoma
This malignant tumour may develop in any nerve. Tumours of the nerve sheath are termed ‘malignant peripheral nerve sheath tumours’, while those originating in the actual nerve fibre may be termed ‘primitive neuroectodermal tumours’ or ‘neuroblastomas’ or ‘ganglioneuroblastomas’.
Malignant fibrous histiocytoma (MFH)
These tumours most commonly develop in muscles, fascia or fatty tissues in limbs. They are firm, rounded tumours rather like liposarcomas or fibrosarcomas. If they are sited deep in the muscle, they may become quite large before they are noticed as they cause few symptoms until a lump is felt.
Angiosarcoma
These malignant tumours may develop in relation to blood vessels or lymph vessels as enlarging vascular masses (clumps containing partly formed blood vessels). They are softish tumours that may contain either blood or lymphatic fluid. Prior to effective antiviral therapy an unusual form of blood-vessel tumour was seen in the skin and gastrointestinal tract of patients with AIDS, called Kaposi’s sarcoma. It is very rare today but is occasionally seen in elderly males of Mediterranean ethnicity.
Synovial sarcoma (synovio sarcoma or malignant synovioma)
This tumour of the synovial membrane is often highly aggressive and malignant, and occurs most commonly in limbs near joints or in association with the sheaths around muscle tendons.
Symptoms and signs
Sarcomas occasionally develop from previously benign tumours of a similar type. Occasionally a previously benign lipoma, for example, will begin to enlarge, showing evidence of a malignant liposarcoma. More often, however, these cancers arise as a local swelling from no apparent pre-existing abnormality. Usually the lump is not painful, although sometimes there is some pain. Occasionally the swelling develops at a site of recent injury. It is more likely, however, that in most cases the injury drew attention to a lump that was already present.
Rarely the first evidence of a soft-tissue sarcoma is found in a chest X-ray showing as secondary lung cancer.
Investigations
The examining doctor will first ask about the lump, especially how long it has been present and if, when and how rapidly it started to enlarge. The lump is measured, the local draining lymph nodes and other lymph nodes examined and a chest X-ray and full blood count performed. An MRI scan, ultrasound and angiography (see Section 2) may also give more information about the tumour, particularly the degree of invasion or compression of surrounding tissues. MRI scans provide more information in this regard than CT scans. The definitive diagnosis is made by a biopsy of the tumour for microscopic examination. The role of PET scanning is still being investigated.
Treatment
The standard treatment of soft-tissue sarcoma is surgical excision. As the risk of local recurrence is high, the surgeon must remove a great deal of apparently normal tissue around the tumour to be as sure as possible that all of the malignant cells have been removed. In some circumstances large tumours in a limb may require amputation. This can sometimes be avoided by using induction (neoadjuvant) chemotherapy or chemo/radiotherapy to shrink the tumour prior to surgery.
In some specialised clinics the chemotherapy can be given by regional infusion into a supplying artery (as in the case of sarcoma in a limb), with good responses in shrinking the cancer. Amputation has been avoided in 80% of patients who would have previously been treated this way. Similar responses are seen if the chemotherapy is given over an hour or so in a ‘closed circuit infusion’, and even better responses have been reported when the immunologic agent TNF is included in the closed circuit.
Although these cancers are usually not particularly sensitive to radiotherapy, chemo/radiotherapy followed by local surgery may allow resection of large cancers, especially in the head, thorax, abdomen or pelvis. Liposarcomas and malignant fibrous histiocytomas are the most common of the soft-tissue sarcomas encountered in this way.
With some sarcomas the risk of secondary spread to the lungs is considerable, and there may be virtue in also giving a postoperative course of adjuvant chemotherapy (see Section 2) to reduce this risk. It appears this may only be of value, however, when the primary sarcoma is located on a limb. In some patients isolated metastases such as those in the lung may be surgically excised.
MALIGNANT TUMOURS OF BONE AND CARTILAGE
Osteosarcoma
A malignant tumour of bone-forming cells is called an osteosarcoma. This is an uncommon but highly malignant form of cancer and tends to affect children and young adults, with the highest incidence between ten and 25 years of age. The cause of osteosarcoma in young people is not known, although it does occur most often in the growth plates (the growing centres) near the bone ends while the patient is still growing.
A rare and incurable osteosarcoma sometimes develops in old people in the site of a chronic bone disease called osteitis deformans (Paget’s disease of bone).
Symptoms and signs
Osteosarcoma usually first develops as a painful swelling near the end of a bone in a child or young adult. This may be associated with overlying redness and sometimes a fever. The swelling may be tender and may at first look like an acute infection in the bone. This sarcoma tends to spread to the lungs early in its course, so best results are achieved if it is diagnosed and treated as soon as possible.
Investigations
Bone X-rays often show a typical appearance of the disease from which a preliminary diagnosis of osteosarcoma can be made. More precise information can be learned from CT studies or MRI studies. PET scanning is still under investigation. However, diagnosis depends on a bone biopsy in which a small piece of the tumour is taken for microscopic examination. Chest CT scans are carried out to look for metastases in the lungs.
Treatment
Prior to the development of effective adjuvant chemotherapy osteosarcoma was fatal in the majority of patients. Treatment was by early amputation of an affected limb, sometimes in combination with radiotherapy, but death usually resulted due to the development of secondary cancer in the lungs.
The outlook has been greatly improved with modern chemotherapy. Nowadays cytotoxic drugs are given as induction (or neoadjuvant) chemotherapy (see Section 2) from the time of diagnosis up to surgery. Not long ago amputation was usually used to remove the primary sarcoma followed by chemotherapy to eradicate any microscopic secondary cancers in the lungs. From a 20% cure rate improvement in survival has increased to over 50%. A further advance has been limb conservation. Instead of amputation, after chemotherapy it is possible in many patients to locally resect the remaining cancer mass. An internal prosthesis made of special metal or plastic is then used to reconstruct the limb. In some specialised centres the induction chemotherapy is given via a cannula inserted into the artery directly supplying the tumour. This combined treatment is very effective in curing more than half of the patients with osteosarcoma, and in 80% of these cases the cure is achieved without amputating the limb.
In some clinics the pre-operative chemotherapy is not given into the artery supplying the limb but is given systemically (into a vein). This is an easier method of giving chemotherapy, and the results of treatment are possibly as good as with intra-arterial chemotherapy for this cancer.
Osteoclastoma (central giant cell tumour of bone)
This cancer occurs most commonly in the ends of the long bones of middle-aged adults. It is a cancer of low-grade malignancy, in that it does not often spread to other organs or tissues but tends to develop locally and commonly recurs locally after attempts at removal.
Symptoms and signs
The first evidence of this tumour is usually swelling, often with pain. It may be first noticed due to a fracture of the weakened bone.
Investigations
X-rays or CT or MRI scans will usually show a typical appearance of this tumour, but diagnosis is established by the surgeon taking a biopsy specimen and having it examined by a pathologist under the microscope.
Treatment
If possible, the tumour is removed surgically. If it is inadequately removed, radiotherapy may be given post-operatively.
A recurrent tumour tends to be more malignant, however, and treatment by amputation may be required.
Ewing’s tumour
This is an uncommon malignant tumour that occurs most often in the shafts of the long bones of adolescents and young adults between the age of ten and the late teenage years. Although it occurs in bones, it is not truly a tumour of bone cells but a tumour of connective tissue in bone.
Symptoms and signs
Pain, swelling, fever and anaemia are common features of Ewing’s tumour, so much so that a diagnosis of infection (osteomyelitis) may be considered. Sometimes lesions are present in more than one bone.
Investigations
X-rays of the bone often show the laminated ‘onion peel’ appearance that is typical of Ewing’s tumour. Further useful information may be gained from CT or MRI studies or from isotope scans. Biopsy and microscopic examination will establish the diagnosis.
This is a tumour where, if available, PET scans may be especially helpful to detect any centres of malignant growth in bones at other sites and to see evidence of a response to chemotherapy and radiotherapy treatment.
Treatment
Standard treatment by surgery (usually amputation) has rarely cured this highly malignant tumour. Adjuvant chemotherapy is critical in preventing metastatic disease.
With modern treatment using chemotherapy, radiotherapy and possibly local surgical excision significantly better results are now being achieved.
Multiple myeloma
This is a malignant tumour of plasma cells, occurring in the bone marrow. Normal plasma cells are derived from lymphocytes, and their role is to produce antibodies in response to infection or vaccination. The malignant plasma cells often produce a single type of antibody-like protein molecule. This is called a paraprotein and can be measured in the blood by special electophoretic tests. The abnormal plasma cells may be scattered through the bone marrow, crowding out the normal (haemopoeitic) marrow that produces red cells, white cells and platelets. This may cause the patient to become anaemic and at risk of infection or bleeding. In some patients the paraprotein may damage the kidneys. Also the plasma cells may form a large number of tumours growing inside bones. These can cause so-called lytic lesions or areas where bone has been dissolved away, resulting in severe pain or even fracture of major bones. If a patient has only one such lesion, this is called a plasmacytoma.
Multiple myeloma most often affects adults over the age of 50, and its cause in most patients is not known. However, radiation exposure is a risk factor, and the disease, for unknown reasons, is more common in African Americans.
Investigations
X-rays may show typical ‘punched out’ or lytic areas in bones. A blood count is taken, as the patients are usually found to have anaemia. The presence of a paraprotein, together with a bone-marrow biopsy, will confirm the diagnosis.
The urine is also examined for a segment of the paraprotein (Bence-Jones protein), which, if present, indicates a diagnosis of multiple myeloma. This protein is also a risk factor for kidney damage.
Treatment
Solitary plasmacytomas are surgically removed, followed by local radiation therapy. Younger patients (i.e. those less than 65–70 years old) can be treated with high-dose chemotherapy and haemopoietic cell support with a cytokine called granulocyte colony-stimulating factor (G CSF) to build up the blood. This can result in disease remission and survival for several years in some patients. This therapy is relatively toxic, however, and requires some weeks in hospital. For older or frailer patients treatment with simpler forms of therapy, including intermittent courses of high-dose cortisone drugs, can be effective. Thalidomide has also been shown to be of value in this disease. It appears to inhibit small-blood-vessel formation in the marrow, thus inhibiting growth of the abnormal plasma cells.
Chondrosarcoma
Chondrosarcoma is a malignant tumour of cartilage and most often affects middle-aged adults. This tumour may develop on any bone, especially at the ends of long bones or in the bones of the pelvis. It is usually first noticed as a slow-growing painful lump on a bone, often near a large joint.
Investigations
X-rays will often show the typical appearance of a chondrosarcoma, but a biopsy is required to establish the diagnosis. CT or MRI studies will help show the exact position, nature and extent of the tumour.
Treatment
If possible, radical surgical excision of the tumour and adjacent bone is carried out. This may require amputation of a limb.
These sarcomas are not sensitive to standard radiotherapy or to chemotherapy, but as they are slow growing and usually do not spread until late in the disease, treatment by radical surgery usually results in cure.
METASTATIC (SECONDARY) CANCER
A secondary or metastatic cancer is a cancer that is growing in an organ or tissue some distance away from the tissue or organ in which it originated. Benign tumours tend to grow very slowly and remain localised to the tissues in which they arise, whereas malignant tumours (cancers) tend to grow more rapidly, to grow into surrounding structures and damage them, and to spread into tissues or organs away from the original or primary site of development.
To spread to distant sites, the malignant cells usually grow into blood vessels or lymph vessels, and clumps of cells break off and are carried by the bloodstream or the lymphatic vessels to a distant organ or tissue, or to lymph nodes, where they may grow as secondary tumours. The spreading cancer cells can be thought of as ‘seeds’ being transported along blood or lymph vessels to a new ‘soil’, where they may take root and grow. Malignant cells may also sometimes spread along nerve sheaths, or across body cavities such as the abdominal cavity or a pleural cavity in the chest.
The most common site for the secondary spread of cancers is via lymph vessels into lymph nodes. First they grow in lymph nodes near the original cancer and then spread into lymph nodes further away. The next most common sites are the lungs or the liver, which they access through the bloodstream.
Other common sites of secondary spread are to bones, under the skin or to the ovaries. No tissue is exempt from developing a secondary cancer. This includes the thyroid, adrenal and other glands, the bowel, brain, spinal cord, limbs, testes, uterus, skin, bladder or kidneys. It should be noted, though, that some organs and tissues tend to have a relatively low incidence of secondary growth of most cancers for no obvious reason. These include the spleen and muscles.
The likelihood of a tumour spreading to a particular site depends very much on the type of tumour and its place of origin. Stomach, pancreas and bowel cancers, for example, tend to spread first to abdominal lymph nodes and to the liver. Breast cancer tends to spread to nearby lymph nodes, usually first to nodes in the armpit and then to more distant lymph nodes, to the liver, lungs and bone. Prostate cancer tends to spread to nearby lymph nodes and to bone. Skin cancer and cancers in the mouth and throat tend to spread to nearby lymph nodes; the exception is BCC, which rarely spreads anywhere other than into surrounding tissues. Melanoma, on the other hand, tends to spread early not only to lymph nodes but to almost any other organ or tissue in the body.
Sarcomas do not usually spread to lymph nodes first: they are more likely to first spread via the bloodstream to the lungs.
More detail about the spread of each different type of cancer has been discussed under the relevant headings earlier in this section. The treatment of secondary cancer depends on the type and site of origin of the particular cancer; treatment has similarly been discussed under the individual headings in this section.