Oncology emergency is an acute event, which can quickly threaten patient’s life. This event can be directly or indirectly related to cancer or to its treatments.
Thus, complicated therapeutic procedures for another disease, possibly offering very important patient benefit, are not always offered under the false pretext that the patient is soon going to die from cancer.
However, many patients are cured from their cancer, and if not may benefit from a long remission enjoying good quality of life. Thus, for emergencies, a short multidisciplinary discussion should be set up in order to institute an appropriate therapeutic project for the other disease the cancer patient is suffering from.
On the other hand, the human mind naturally attempts to unite all of the symptoms into one unique disease: but cancer patients may suffer life threatening emergencies from a totally different origin.
Thus, even in a cancer centre, the clinical diagnosis of an emergency situation should include all pathologies and consequently involves good knowledge of internal and emergency medicine.
Sometimes, patients are addressed to the cancer centre by their general practitioner or by local emergency services because patients have been treated there. In fact, it would be wiser to send the patients to a cardiological intensive care unit (or specialised respiratory, metabolic, infectious units, or to a competent surgeon).
A delay may therefore be observed during which patients wait in the emergency room of cancer centre before being sent to the most appropriate hospital for their situation. If not always harmful, this delay is always an unnecessary supplementary discomfort due to further emergency transport.
Decision not to resuscitate :
Contrary to the discussion on the previous page, patients at a terminal stage of their disease and who do not respond to any cancer therapy should not be resuscitated, with the exclusion of a few exceptional circumstances.
There is no use in letting a patient die 'twice' by resuscitating someone we cannot help when he/she is alive again. Failing to resuscitate a dying patient is neither passive nor active euthanasia: it is simply accepting our mortal humanity.
The anticipation of cancer development, patient preparation and dialogue with family, together with clear instructions in the patient’s medical record should avoid futile resuscitation.
However, this ‘do not resuscitate’ decision should never been taken alone. The physician should discuss with the care team and of course with the patient and his/her family.
For the well-informed, pain-relieved patient, death becomes the unfortunately unavoidable friendly end of life which is accepted as a deliverance from the deterioration of the pre-terminal phase.
The patient’s family should be prepared for this evolution and should accept it with loving consideration for the patient.
Some families want to fight up to the very end. Emotionally, they cannot accept that their patient is going to die. Most often, there are many family conflicts behind such refusal (angered child, financial disputes, remorse or reproaches concerning very old deeds, etc…) which can sometimes be resolved through a discreet open dialogue.
On the contrary, other families would like to precipitate events because their patient’s suffering and mainly their own distress become unbearable.
Carers should also be prepared (some refuse to accept reality) and the decision not to resuscitate should be taken after discussion within the team. Specific and precise instructions should be written, dated and signed by the physician who can always be called by the care team if necessary.
Carer loneliness vis-à-vis a dying person may become catastrophic and lead to euthanasia errors (killing the patient by mercy) with considerable future suffering for the carer.
Sudden death:
Cancer is often the reason for sudden death and the patient, once resuscitated, may enjoy prolonged survival for a few months or even be cured. Certain statistics show that the median survival after cardio-respiratory resuscitation is around 6 months, which is higher than the survival observed after sudden deaths accompanying complicated liver cirrhosis or major cardiac insufficiency. On the other hand, in autopsy studies, unknown cancer is rarely responsible for sudden death.
Direct cardiac involvement is not rare with tumour endocarditis (marantic endocarditis) and even direct invasion of the myocardium by bronchial tumours.
Iatrogenic myocardial complications (i.e. induced by therapy) are frequent: exceptionally due to irradiation (the myocardium is a muscle which is resistant to radiotherapy except in the case of major vascular disease), direct myocardic cell involvement by chemotherapy agents such as anthracyclins (in relation to cumulative dosage), coronary endothelial cell involvement induced by cyclophosphamide, coronary spasm during 5-FU infusion, more rarely direct myocardium involvement due to cisplatin and taxans).
Lastly, some therapies may induce a congestive cardiac failure (Interleukin, Interferon, Taxotere).
Fluid accumulation is provoked by the inflammatory reaction which is in turn related to the localised haemorrhage induced by the tumour implant. Generally, diagnosis can be made by echocardiography or chest radiography before any clinical symptoms appear.
Few clinical symptoms are initially observed: slight dyspnoea, imprecise thoracic pain, coughing, lower limb oedema. Then major symptoms appear with massive pain, right cardiac insufficiency, jugular distension, liver pain, and widening of the cardiac image on radiography.
Evolution may accelerate towards terminal diastolic cardiac insufficiency.
Emergency treatment involves the decompression of the pericardium by pericardiocentesis or surgical pericardectomy or derivation.
Aetiological treatment (i.e. chemotherapy) should then be rapidly instituted.
Such life-saving treatment is most useful among patients with chemosensitive tumours (lymphoma, leukaemia) for whom complete remission is possible after such an acute complication.
Pulmonary embolisms are most often massive obstructing more than 50% of the vascular pulmonary bed and result in acute right cardiac insufficiency, with pulmonary hypo-perfusion followed by pulmonary shock. Previous multiple small embolisms may also very quickly produce such symptomatology.
Diagnosis is established by clinical examination, arterial hypoxemia, electrocardiogram (the classical but rare S1-Q3 syndrome), ventilation-perfusion radio-nuclide lung scan (xenon, technetium). Pulmonary angiogram is often too aggressive; new CT scan might be useful.
Treatment includes all the resuscitation procedures, anticoagulant treatment. If the patient’s cancer prognosis is good, a thrombolytic treatment (streptokinase, urokinase) may also be proposed.
In patients with heavy risk of multiple embolism, cava vena umbrellas or filters may be inserted percutaneously under local anaesthesia.
Patients with brain tumours may bleed into the brain or have a massive oedema and cerebral hernia resulting in sudden death.
Patients with long lasting leucopoenia may suffer from sudden septic shock. Thus a patient with a febrile neutropoenia, whose fever does not quickly retrocede with antibiotics, should be hospitalised.
Other causes of sudden death may come from undetected metabolic disorders: major hypercalcaemia, severe hyponatraemia with major dehydration, hyperkaliaemia in relation to renal insufficiency or hypokaliaemia due to massive water loss).
Fractures :
Thus, two simultaneous events occur: an osteolytic bone lesion and a traumatism which can be minimal.
There is no clear correlation between the radiological importance of bone metastases and the occurrence of fractures.
The commonest fracture sites are the vertebrae (pathological collapse with risk of neurological complications), femur (neck but also diaphysis), humerus, ribs, iliac bone and particularly the cotyloid cavity.
When such effort pains occur in cancer patients, x-rays should be quickly performed to verify bone structure (especially the thickness of the cortical bone) in order to possibly propose preventive surgery.
Preventive surgery will be proposed when the cortical bone is profoundly and largely destroyed (2 to 3 cm), when the bone shaft is destroyed over 50% of its width or when radiotherapy does not improve pain (radiotherapy cannot relieve mechanical pain).
Leaving an immobilised patient to suffer in bed and die from confinement complications constitutes a great failure in our capacity to mobilise carers for the patient’s benefit. It is a genuine ethical error.
Orthopaedic action offers very quick relieve of the mechanical aspect of bone pain, and often also of its inflammatory aspect (hyper-pressure is one of the causes of metastatic bone pain and may be relieved by the local bleeding induced by surgery). Secondarily, the surgical procedure can be followed by palliative analgesic radiotherapy.
The psychological impression is of great importance for the patient and his/her family: the idea that carers do not abandon their patients, so ’something can still be done’.
The patient recovers, for a given period of time, a ‘normal’ life and concentrates his/her whole energy on walking or using the restored limb.
After the adversity of fracture and the doubt before a surgical decision, comes a new psychological surge of will and hope.
Among the most frequently proposed procedures: total hip replacement prosthesis, centromedullar or interlocking nails, replacement of a vertebral body with cement, resection of a vertebral lamina with liberation of nerve root, decompression of spinal cord).
Superior vena cava syndrome :
Other frequently responsible cancers are: lymphoma, breast cancer, mediastinal geminal tumours, thymoma and various others.
Due to the anatomical configuration, superior vena cava syndrome is observed four times more frequently on the right.
Differential diagnoses are rare: idiopathic mediastinal fibrosis, histoplasmosis, venous thrombosis related to a catheter or surgery. In fact, all pathological processes which invade or destroy the lymph structures of the superior mediastinum may provoke an obstruction to the return of venous blood and thrombosis.
Its severity depends on:
The revealing patient complaint is dyspnea, coughing, headache and facial swelling. Then, neck, chest and upper limb swelling is observed. All of these symptoms are worsened when the patient bends forwards. Diagnosis is evident as soon as this is evoked.
In reality, the development of superior vena cava syndrome is rarely acute (most often neglected). Half of the patients reveal their cancer through this syndrome. Chest radiography and thoracic scan are the best imaging procedures before a diagnostic biopsy.
You can view a typical case of superior vena cava with thrombosis and important collateral circulation.
Other palliative measures are semi-seated position, rest, oxygen and short courses of corticosteroids.
A poor response to aetiological and palliative treatment suggests concurrent thrombosis which may require further anticoagulant treatment.
Unfortunately, most superior vena cava syndromes relapse since underlying cancer is not cured by treatment (lung cancer). The use of intravenous stents has been suggested in order to avoid acute complications.
Haemorrhages :
The reasons for bleeding are numerous:
In the stomach, the most frequent cause is haemorrhagic gastritis and peptic ulcer, which complicate treatment by anti-inflammatory drugs, corticosteroids or occurring during septicaemia with renal and hepatic insufficiency.
Direct involvement of the digestive wall is rare (except in the case of primitive lesions). The famous Mallory-Weiss syndrome (haemorrhage due to intense vomiting) is rarely severe.
Haemorrhage of the inferior digestive tract is most often related to a benign intestinal lesion or to treatment side-effects (such as rectal haemorrhage after radiotherapy for gynaecological or urinary cancers). These haemorrhages are difficult to treat (local corticosteroids, cauterisation with laser beam).
The most frequently concerned cancer is epidermoid lung cancer since it invades blood vessels and is highly necrotic.
Another frequent cause of hemoptysis is pulmonary aspergillosis which often occurs in immunodeprived patients (after prolonged chemotherapy).
More rarely, hemoptysis is related to therapy (laser, endobronchial brachytherapy).
Treatment includes very simple measures such as adopting a semi-seated position, oxygenation, aspiration, and a rapid search for the aetiology (bronchosopy if the patient’s status permits).
In terminal hemoptysis, patient anxiety should be relieved (subcutaneous morphine, midazolam), and a carer/family member should remain at the patient’s bedside until sleeping.
If no efficient aetiological treatment is possible (surgery for instance), various techniques have been proposed such as a Fogarty catheter, arterial embolisation, radiotherapy or laser beam.
The main reasons for rupture are post-surgical infection, ligature failure, wound breakdown after radiotherapy and direct tumour invasion of the artery. With the recent progress in surgery and radiotherapy, this complication is becoming rarer.
This rupture never occurs on a healthy mucosa or skin. Most often, a wound infection or tumour infection, exposure of a vessel or vessel necrosis with small revealing haemorrhages are present.
The prophylactic ligature of the internal carotid prevents massive haemorrhage with a potential risk of underlying cerebral ischemia. It avoids the necessity for urgent carotid ligature if massive haemorrhage does occur.
This cataclysmal haemorrhage is a most terrifying event for the patient, the family but also for every unprepared caregiver.
When this event is expected and when no ligature is feasible, the therapeutic procedure should be prepared, in particular the sedative hypnotic drugs to be infused when the cataclysm occurs as well as the thick dressing requried to hide the massive bleeding from the patient and his/her family. In terminal haemorrhage, treatment simply consists in blood vessel compression and patient sedation. Death occurs in a few minutes.
If the haemorrhage occurs when therapeutic solutions are still possible (such as salvage surgery), then treatment should be active with compression and emergency ligature of the carotid artery, with the risk of vascular complications (hemiplegia). A programmed carotid ligature is always easier and more efficient than an emergency ligature.
They require the ligature of one or both external carotid arteries with the constant necessity to maintain the airways free for breathing.
Occasionally, as in internal carotid rupture, massive oral haemorrhage is a terminal event. Patient sedation should be very quickly administered in order to avoid suffocation by patient’s own blood.
Epistaxis is rarely life-threatening and spontaneously stops with nose compression or nose packing.
When epistaxis is posterior, it requires posterior packing during pharyngoscopy.
Bleeding from ethmoidal tumours generally requires adequate surgical treatment or embolisation.
In relapsing massive badder haemorrhages, laser beam, haemostatic irradiation, hypogastric artery embolisation, hypogastric artery surgical ligature or sometimes haemostatic cystectomy have been proposed.
Generally these nodes have been irradiated and suturing the bleeding femoral artery is almost impossible.
Thus, as for carotid artery ruptures, clear measures should be taken in order to minimise the dramatic and
traumatic nature of patient death.
Respiratory emergencies :
Clinical symptoms are hypoxia, dyspnoea, tachycardia, peripheral vasoconstriction, agitation, confusion and even obnubilation with cyanosis leading to respiratory distress.
Acute respiratory insufficiency has many causes ranging from mechanical tracheal disorders to alveoli exchange disorders or neurological disorders altering the respiratory mechanism.
A precise evaluation of the mechanisms of respiratory insufficiency is necessary to decide on a potentially efficient treatment.
Among the various aetiologies:
It associates a very rapidly developing hypoxia, with diffuse multilobular infiltration at chest x-ray, similar to non-cardiogenic pulmonary oedema, with diminution of pulmonary compliance and arteriovenous shunt.
It is a diffuse alveolar disease and a non-specific lung reaction to major aggression.
Such acute respiratory insufficiency requires patient admission into an intensive care unit.
Its prognosis is very poor: nearly 90% of patients with lung cancer, 40% with breast cancer who are admitted into an intensive care unit for respiratory assistance die in the month following their admission. Such a high mortality rate may question the appropriateness of admission of these patients into intensive care units.
In fact, treatment is symptomatic with high oxygen supply which almost always requires endotracheal intubation, multiple aspirations, and machine-assisted ventilation in order to maintain oxygen saturation over 90%. Other cardiovascular rehabilitation measures and antibiotics are also necessary.
Pleural puncture can be both of diagnostic and therapeutic value with a clear improvement of dyspnoea. It can be complicated by pneumothorax, haemorrhage, empyema or cancer cell sowing along the puncture path.
In the case of frequent or rapid relapse, intrapleural chemotherapy may be proposed (if such chemotherapy is potentially effective) or simple talc pleurodesis which will allow the drying of pleural effusion over a long period of time.
Obstructive lesions are manifested by coughing, dyspnoea, stridor, cyanosis, atelectasia and possibly death.
Upper airway obstruction
Upper airway obstruction constitutes a genuine medical emergency.
They are due either to the intrabronchial aspiration of food or saliva, or to tracheal stenosis, tracheomalacia, oedema or a complication related to treated tumours (in particulare oedema).
Diagnosis is evoked by major inspiration difficulties with intercostal muscle retraction and major psychological distress. Acute transformation may be very rapid: the patient becomes cyanosed, unable to speak and extremely agitated before dying within a few minutes.
The endoscopic examination should be carried out quickly in order to find out the cause of the obstruction and to treat it if possible (removal of a foreign body, aspiration of a mucous mass). Occasionally, rapid tracheotomy needs to be performed.
As soon as the risk of asphyxia has been removed, all necessary measures should be taken to avoid any feared relapse of such acute obstruction.
Lower airway obstruction
It is rarely such an acute phenomenon. It is generally due to bronchial carcinoma or a metastatic endobronchial lesion.
The obstruction usually provokes hemoptysis, dyspnoea and fever with obstructive pneumonia.
Fiber bronchoscopy generally allows the evaluation of the endobronchial lesion and consequently the proposal of appropriate treatment (surgery, radiotherapy, chemotherapy or an association).
A symptomatic treatment may also be proposed (laser, endobronchial brachytherapy, endobronchial stent).
The risk involved in lung aspiration of a gastric liquid with a low pH, especially for intubated patients or tube fed patients, is the constitution of alveolar lesions associated with super-infection due to aspirated food.
Massive aspiration can provoke death by suffocation.
Most often, after the initial endobronchial aspiration, the patient coughs and ejects most of the inhaled material; however a few hours later, an increasing dyspnoea accompanied by coughing, fever, hypoxemia and pulmonary oedema signifies the onset of an acute respiratory distress syndrome.
Occasionally, the endobronchial inhalation of alimentary liquid remains totally unnoticed and a chronic infection appears a few days later.
Treatment includes respiratory rehabilitation, antibiotics, tracheobronchial aspiration and bronchoscopic washings with physiological fluid.
Metabolic emergencies (1) :
If osteolytic lesions are present, then hypercalcaemia is generally a late phenomenon underlining poor prognosis. Hypercalcaemia induces symptoms that should be corrected with efficient palliative care.
Many hypercalcaemia appear without any osteolytic lesions and are therefore true paraneoplastic syndromes possibly due to several mechanisms:
Untreated hypercalcaemia leads to severe dehydration and possibly to patient death by cardiac rhythm disorders.
However, diphosphonates (in particular intravenous forms) have totally modified such modalities allowing ambulatory treatment over several weeks, with prolonged survival and good quality of life.
The only major point to ensure is correct patient rehydration, if necessary intravenously. Corticosteroids are still useful if hypercalcaemia is very high.
Metabolic emergencies (2):
Hyponatraemia is often observed in preterminal stages of severe disease. Patients excrete the sodium excesses administered in order to correct hyponatraemia and liquid restriction leads to more severe dehydration than that already observed. Surprisingly, if patients are able to resume normal eating, a spontaneous correction of hyponatraemia is observed.
Thus, this preterminal hyponatraemia should be distinguished from an inappropriate secretion of ADH which is a genuine paraneoplastic syndrome (occurring in lung cancer for instance). Hyponatraemia leads to severe neurological disorders and to an exaggerated water excretion by the kidney (excessive urinary osmolality). In such cases, fluid restriction is useful, but more particularly the treatment of cancer, where possible, will improve the clinical situation.
Another frequent cause of hyponatraemia in cancer patients is the presence of oedema leading to a dilution syndrome. Such a clinical situation can be observed when ascitis or major pleural effusion occur. Whereas symptomatic treatment (ascitic puncture, diuretics) may be useful, only aetiological treatment will actually correct hyponatraemia for a reasonably long time.
This syndrome is observed for cancers with very quick tumour growth, important cellular turnover, important tumour burden and great sensitivity to chemotherapy (or radiotherapy) such as leukaemia, high grade lymphoma, small cell lung carcinoma or myeloma.
Uric acid is the final degradation product of purinic nucleic acid: in urine, the acidity transforms the sodium form into uric acid which is not very soluble at this pH level. Crystals appear and provoke an obstructive nephropathy and, secondarily, renal insufficiency. In the case of massive cellular necrosis induced by chemotherapy, we can also observe hyperkaliaemia and hyperphosphataemia with hypocalcaemia, thus involving a risk of cardiac arrhythmia and sudden death.
The urological syndrome generally appears two days after chemotherapy.
Treatment includes massive hydration but more importantly prevention by systematic prophylactic administration of allopurinol a few days before the beginning of chemotherapy. This drug blocks xanthine oxydase and inhibits the formation of uric acid. Another important point is to alkalinise urines and obtain major diuresis through infusion before chemotherapy (at least three litres per day).
Infections and cancer :
Infections are one of the main problems in haematology: around 80% of patients with acute leukaemia, 75% of patients with lymphoma and 50% of those with myeloma will, at some stage, contract severe infection. In solid tissue oncology, infections are less frequent, with the exception of cases of intensive treatment or during the pre-palliative phase.
The infectious risk is only increased when neutropenia falls under 1,000 per mm3, however it becomes very serious under 500 polymorphonuclears (PMN) per mm3 and almost constant when PMN counts are under 100 per mm3. The intensity of nadir (the lowest point on the curve), is far less important for infectious risk than the duration of this nadir. After a few days with a PMN level below 100 per mm3, the infectious risk is almost constant and requires preventive isolation measures.
Occasionally, patients suffer no severe neutropenia but an alteration of their phagocyte functions in relation to chemotherapy, resulting in the same effect.
Neutropenic patients do not express infections in the same manner as patients with normal leukocyte counts: they cannot produce pus or inflammation. For instance, they may have a severe lung infection, without purulent expectoration, but rather rapid respiratory insufficiency with pulmonary lesions which can very quickly become irreversible (necrosis without PMN reaction).
In a similar manner, they do not have pus in their urine but only bacteria. They do not harbour abscesses but necrosing lesions.
The most frequent sites of infection for these patients are: the throat, the lung, the urine, the skin and the perineal regions, and most infectious germs are those generally present in the patient’s body. Preventive measures are therefore most useful, in particular careful body washing.
Among them, those expressed within the cell are the most fearsome.
For instance, bacterial infections with mycobacteria, listeria, nocardia, legionella, but also fungi infections with cryptoccoques, histoplasma, pneumocystis carinii, toxoplasmosis, or viral infections by cytomegalovirus or herpes simplex virus.
The difficulty in performing vaccinations during chemotherapy is also noteworthy.
The obstruction of respiratory airways or digestive tracts also leads to a slowing of normal excreta flow (bronchial retention, intestinal occlusion).
The aggression of digestive or respiratory mucosae by chemotherapy (or radiotherapy) also promotes local super infection.
bacterial infections,
fungal infections,
viral infections,
parasitic infections.
The spectrum of bacterial infections is changing following modifications in hospital eco-systems, in reaction to antibiotic prescriptions.
The following table shows the recent evolution of bacterial infections:
This table shows that 20% of clinically documented infection could not be bacteriologically documented. For 50% of observed fevers, we have no clinical or bacteriological proof of infection.
Certain strains (such as streptococcus viridans or streptococcus beta-haemolytic) may lead to severe septicaemia, with a risk of shock and secondary localised infections resistant to classical penicillin-based drugs.
A precise antibiogram is also necessary to correctly adjust antibiotics.
Techniques identifying bacterial antigens or bacterial DNA allows the shortening of this identification delay to a few hours if necessary.
Fungi Infections :
Fungi infections are complications that are most frequently observed among immunodepressed patients (either after haematological cancer or after an intense chemotherapy regimen or during the preterminal phase).
We can distinguish:
Viral infections :
Viral infections are frequent during anti-cancer treatment and in immunodepressed subjects. Sometimes previous viral infections may reappear.
Parasitic infections :
In this chapter, we will only discuss opportunistic parasitic infections which can be observed in our country and not those observed in subjects residing in countries harbouring endemic parasitic infections.
Main chapters
General considerations :General considerations
Sudden death
Syncope and falls
Fractures and impending fracture syndromes
Medullary compression
Cava superior syndrome
Haemorrhages
Respiratory emergencies
Metabolic emergencies
Infections
Non-cancer-related emergencies
A general tendency among physicians who treat few or no cancer patients is to assimilate, as does the general public, cancer and quick death.Thus, complicated therapeutic procedures for another disease, possibly offering very important patient benefit, are not always offered under the false pretext that the patient is soon going to die from cancer.
However, many patients are cured from their cancer, and if not may benefit from a long remission enjoying good quality of life. Thus, for emergencies, a short multidisciplinary discussion should be set up in order to institute an appropriate therapeutic project for the other disease the cancer patient is suffering from.
On the other hand, the human mind naturally attempts to unite all of the symptoms into one unique disease: but cancer patients may suffer life threatening emergencies from a totally different origin.
Thus, even in a cancer centre, the clinical diagnosis of an emergency situation should include all pathologies and consequently involves good knowledge of internal and emergency medicine.
Sometimes, patients are addressed to the cancer centre by their general practitioner or by local emergency services because patients have been treated there. In fact, it would be wiser to send the patients to a cardiological intensive care unit (or specialised respiratory, metabolic, infectious units, or to a competent surgeon).
A delay may therefore be observed during which patients wait in the emergency room of cancer centre before being sent to the most appropriate hospital for their situation. If not always harmful, this delay is always an unnecessary supplementary discomfort due to further emergency transport.
Decision not to resuscitate :
Contrary to the discussion on the previous page, patients at a terminal stage of their disease and who do not respond to any cancer therapy should not be resuscitated, with the exclusion of a few exceptional circumstances.
There is no use in letting a patient die 'twice' by resuscitating someone we cannot help when he/she is alive again. Failing to resuscitate a dying patient is neither passive nor active euthanasia: it is simply accepting our mortal humanity.
The anticipation of cancer development, patient preparation and dialogue with family, together with clear instructions in the patient’s medical record should avoid futile resuscitation.
However, this ‘do not resuscitate’ decision should never been taken alone. The physician should discuss with the care team and of course with the patient and his/her family.
For the well-informed, pain-relieved patient, death becomes the unfortunately unavoidable friendly end of life which is accepted as a deliverance from the deterioration of the pre-terminal phase.
The patient’s family should be prepared for this evolution and should accept it with loving consideration for the patient.
Some families want to fight up to the very end. Emotionally, they cannot accept that their patient is going to die. Most often, there are many family conflicts behind such refusal (angered child, financial disputes, remorse or reproaches concerning very old deeds, etc…) which can sometimes be resolved through a discreet open dialogue.
On the contrary, other families would like to precipitate events because their patient’s suffering and mainly their own distress become unbearable.
Carers should also be prepared (some refuse to accept reality) and the decision not to resuscitate should be taken after discussion within the team. Specific and precise instructions should be written, dated and signed by the physician who can always be called by the care team if necessary.
Carer loneliness vis-à-vis a dying person may become catastrophic and lead to euthanasia errors (killing the patient by mercy) with considerable future suffering for the carer.
Sudden death:
General considerations
Sudden death can be defined as death occurring without any warning within one or two hours. Since cerebral hypoxia leads to irreversible disorders in around 5 minutes, it is of utmost importance that the decision to resuscitate the patient or not be taken as quickly as possible.Cancer is often the reason for sudden death and the patient, once resuscitated, may enjoy prolonged survival for a few months or even be cured. Certain statistics show that the median survival after cardio-respiratory resuscitation is around 6 months, which is higher than the survival observed after sudden deaths accompanying complicated liver cirrhosis or major cardiac insufficiency. On the other hand, in autopsy studies, unknown cancer is rarely responsible for sudden death.
Main causes of sudden death
Myocardial disease
Many cancers have the same aetiological factors (tobacco, high animal fat consumption, sedentary life, obesity, alcohol) as other diseases due to coronary arteriosclerosis, arteritis or cerebral vascular disease. Thus, ventricular fibrillation or massive cardiac infarction may often be the cause of sudden death syndrome. If the patient is in clinical remission and/or has a good possibility of being cured or relieved for a long period of time, he/she should receive the same cardiological resuscitation as a non-cancer patient.Direct cardiac involvement is not rare with tumour endocarditis (marantic endocarditis) and even direct invasion of the myocardium by bronchial tumours.
Iatrogenic myocardial complications (i.e. induced by therapy) are frequent: exceptionally due to irradiation (the myocardium is a muscle which is resistant to radiotherapy except in the case of major vascular disease), direct myocardic cell involvement by chemotherapy agents such as anthracyclins (in relation to cumulative dosage), coronary endothelial cell involvement induced by cyclophosphamide, coronary spasm during 5-FU infusion, more rarely direct myocardium involvement due to cisplatin and taxans).
Lastly, some therapies may induce a congestive cardiac failure (Interleukin, Interferon, Taxotere).
Pericardial tamponade
Malignant pericardial effusion is the main cause of pericardial tamponade during cancer. It is generally due to metastatic lesions: lung cancer, breast cancer, oesophageal cancer, lymphoma, leukaemia, melanoma or secondary mesothelioma.Fluid accumulation is provoked by the inflammatory reaction which is in turn related to the localised haemorrhage induced by the tumour implant. Generally, diagnosis can be made by echocardiography or chest radiography before any clinical symptoms appear.
Few clinical symptoms are initially observed: slight dyspnoea, imprecise thoracic pain, coughing, lower limb oedema. Then major symptoms appear with massive pain, right cardiac insufficiency, jugular distension, liver pain, and widening of the cardiac image on radiography.
Evolution may accelerate towards terminal diastolic cardiac insufficiency.
Emergency treatment involves the decompression of the pericardium by pericardiocentesis or surgical pericardectomy or derivation.
Aetiological treatment (i.e. chemotherapy) should then be rapidly instituted.
Such life-saving treatment is most useful among patients with chemosensitive tumours (lymphoma, leukaemia) for whom complete remission is possible after such an acute complication.
Pulmonary embolism
Massive pulmonary embolism is an under-recognised cause of sudden death. Cancer patients have two to three times more thrombosis and embolism than non-cancer patients. Most pulmonary emboli are multiple, originating from deep veins from lower limbs, pelvis or central venous catheters.Pulmonary embolisms are most often massive obstructing more than 50% of the vascular pulmonary bed and result in acute right cardiac insufficiency, with pulmonary hypo-perfusion followed by pulmonary shock. Previous multiple small embolisms may also very quickly produce such symptomatology.
Diagnosis is established by clinical examination, arterial hypoxemia, electrocardiogram (the classical but rare S1-Q3 syndrome), ventilation-perfusion radio-nuclide lung scan (xenon, technetium). Pulmonary angiogram is often too aggressive; new CT scan might be useful.
Treatment includes all the resuscitation procedures, anticoagulant treatment. If the patient’s cancer prognosis is good, a thrombolytic treatment (streptokinase, urokinase) may also be proposed.
In patients with heavy risk of multiple embolism, cava vena umbrellas or filters may be inserted percutaneously under local anaesthesia.
Miscellaneous causes of sudden death
Massive haemorrhage (exteriorised or not) frequently occurs for head and neck cancer, lung cancer, oesophageal or gastric cancer.Patients with brain tumours may bleed into the brain or have a massive oedema and cerebral hernia resulting in sudden death.
Patients with long lasting leucopoenia may suffer from sudden septic shock. Thus a patient with a febrile neutropoenia, whose fever does not quickly retrocede with antibiotics, should be hospitalised.
Other causes of sudden death may come from undetected metabolic disorders: major hypercalcaemia, severe hyponatraemia with major dehydration, hyperkaliaemia in relation to renal insufficiency or hypokaliaemia due to massive water loss).
Fractures :
General considerations
Pathological fractures result from the loss of mechanical bone sustaining functions in relation to their metastatic involvement.Thus, two simultaneous events occur: an osteolytic bone lesion and a traumatism which can be minimal.
There is no clear correlation between the radiological importance of bone metastases and the occurrence of fractures.
The commonest fracture sites are the vertebrae (pathological collapse with risk of neurological complications), femur (neck but also diaphysis), humerus, ribs, iliac bone and particularly the cotyloid cavity.
Impending fractures
Quite frequently, fractures are preceded by bone pain which may occur at rest but is most severe when the bone structure responds to a load (like walking, sitting, wearing an object). This is called the pre-fracture syndrome.When such effort pains occur in cancer patients, x-rays should be quickly performed to verify bone structure (especially the thickness of the cortical bone) in order to possibly propose preventive surgery.
Preventive surgery will be proposed when the cortical bone is profoundly and largely destroyed (2 to 3 cm), when the bone shaft is destroyed over 50% of its width or when radiotherapy does not improve pain (radiotherapy cannot relieve mechanical pain).
Orthopaedic surgery
Orthopaedic surgery should be proposed when the life expectancy is longer than one or two months and when no absolute contra-indications exist (such as major respiratory insufficiency, terminal cardiac insufficiency) although some acts could be performed under local anaesthesia.Leaving an immobilised patient to suffer in bed and die from confinement complications constitutes a great failure in our capacity to mobilise carers for the patient’s benefit. It is a genuine ethical error.
Orthopaedic action offers very quick relieve of the mechanical aspect of bone pain, and often also of its inflammatory aspect (hyper-pressure is one of the causes of metastatic bone pain and may be relieved by the local bleeding induced by surgery). Secondarily, the surgical procedure can be followed by palliative analgesic radiotherapy.
The psychological impression is of great importance for the patient and his/her family: the idea that carers do not abandon their patients, so ’something can still be done’.
The patient recovers, for a given period of time, a ‘normal’ life and concentrates his/her whole energy on walking or using the restored limb.
After the adversity of fracture and the doubt before a surgical decision, comes a new psychological surge of will and hope.
Among the most frequently proposed procedures: total hip replacement prosthesis, centromedullar or interlocking nails, replacement of a vertebral body with cement, resection of a vertebral lamina with liberation of nerve root, decompression of spinal cord).
Superior vena cava syndrome :
Aetiology
Superior vena cava syndrome is related to cancer in almost 90% of cases and especially to lung cancers (among them small cell carcinoma).Other frequently responsible cancers are: lymphoma, breast cancer, mediastinal geminal tumours, thymoma and various others.
Due to the anatomical configuration, superior vena cava syndrome is observed four times more frequently on the right.
Differential diagnoses are rare: idiopathic mediastinal fibrosis, histoplasmosis, venous thrombosis related to a catheter or surgery. In fact, all pathological processes which invade or destroy the lymph structures of the superior mediastinum may provoke an obstruction to the return of venous blood and thrombosis.
Clinical presentation
Its onset is generally insidious.Its severity depends on:
- rapidity of the obstructive process,
- thrombosis syndrome,
- precise location of the obstruction,
- possibility and rapidity of the constitution of collateral circulation.
The revealing patient complaint is dyspnea, coughing, headache and facial swelling. Then, neck, chest and upper limb swelling is observed. All of these symptoms are worsened when the patient bends forwards. Diagnosis is evident as soon as this is evoked.
In reality, the development of superior vena cava syndrome is rarely acute (most often neglected). Half of the patients reveal their cancer through this syndrome. Chest radiography and thoracic scan are the best imaging procedures before a diagnostic biopsy.
You can view a typical case of superior vena cava with thrombosis and important collateral circulation.
Treatment
Most cancers, which are discovered via this syndrome, are more and less chemosensitive (small cell lung cancer, lymphoma, germ tumours). Chemotherapy is therefore the choice treatment. In less chemosensitive tumours, radiotherapy may be a good palliative option.Other palliative measures are semi-seated position, rest, oxygen and short courses of corticosteroids.
A poor response to aetiological and palliative treatment suggests concurrent thrombosis which may require further anticoagulant treatment.
Unfortunately, most superior vena cava syndromes relapse since underlying cancer is not cured by treatment (lung cancer). The use of intravenous stents has been suggested in order to avoid acute complications.
Haemorrhages :
General considerations
Haemorrhage is the third most frequent cause of cancer death (after organ failure due to tumour invasion and infectious complications) and the second among patients with haematological disorders.The reasons for bleeding are numerous:
- Lesion of a vascular vessel (capillary or larger vessel),
- Diffuse superficial bleeding which occurs after thrombocytopenia (iatrogenic or not), particularly in the case of associated infection,
- Bleeding related to abnormally low level of coagulation factors (intravascular coagulation).
Acute gastro-intestinal haemorrhages
Although these haemorrhages are quite frequent (either due to cancer, haemostasis abnormalities or local ulcerations), they are rarely massive enough to threaten the patient’s life.In the stomach, the most frequent cause is haemorrhagic gastritis and peptic ulcer, which complicate treatment by anti-inflammatory drugs, corticosteroids or occurring during septicaemia with renal and hepatic insufficiency.
Direct involvement of the digestive wall is rare (except in the case of primitive lesions). The famous Mallory-Weiss syndrome (haemorrhage due to intense vomiting) is rarely severe.
Haemorrhage of the inferior digestive tract is most often related to a benign intestinal lesion or to treatment side-effects (such as rectal haemorrhage after radiotherapy for gynaecological or urinary cancers). These haemorrhages are difficult to treat (local corticosteroids, cauterisation with laser beam).
Massive hemoptysis
Massive bronchial haemorrhage (hemoptysis) is rarely involved in patient death in lung cancer. The flooding of the bronchial tubes is far more life-threatening than the actual quantity of blood lost.The most frequently concerned cancer is epidermoid lung cancer since it invades blood vessels and is highly necrotic.
Another frequent cause of hemoptysis is pulmonary aspergillosis which often occurs in immunodeprived patients (after prolonged chemotherapy).
More rarely, hemoptysis is related to therapy (laser, endobronchial brachytherapy).
Treatment includes very simple measures such as adopting a semi-seated position, oxygenation, aspiration, and a rapid search for the aetiology (bronchosopy if the patient’s status permits).
In terminal hemoptysis, patient anxiety should be relieved (subcutaneous morphine, midazolam), and a carer/family member should remain at the patient’s bedside until sleeping.
If no efficient aetiological treatment is possible (surgery for instance), various techniques have been proposed such as a Fogarty catheter, arterial embolisation, radiotherapy or laser beam.
Carotid artery rupture
Rupture of the internal carotid artery remains a frequent complication in head and neck cancers.The main reasons for rupture are post-surgical infection, ligature failure, wound breakdown after radiotherapy and direct tumour invasion of the artery. With the recent progress in surgery and radiotherapy, this complication is becoming rarer.
This rupture never occurs on a healthy mucosa or skin. Most often, a wound infection or tumour infection, exposure of a vessel or vessel necrosis with small revealing haemorrhages are present.
The prophylactic ligature of the internal carotid prevents massive haemorrhage with a potential risk of underlying cerebral ischemia. It avoids the necessity for urgent carotid ligature if massive haemorrhage does occur.
This cataclysmal haemorrhage is a most terrifying event for the patient, the family but also for every unprepared caregiver.
When this event is expected and when no ligature is feasible, the therapeutic procedure should be prepared, in particular the sedative hypnotic drugs to be infused when the cataclysm occurs as well as the thick dressing requried to hide the massive bleeding from the patient and his/her family. In terminal haemorrhage, treatment simply consists in blood vessel compression and patient sedation. Death occurs in a few minutes.
If the haemorrhage occurs when therapeutic solutions are still possible (such as salvage surgery), then treatment should be active with compression and emergency ligature of the carotid artery, with the risk of vascular complications (hemiplegia). A programmed carotid ligature is always easier and more efficient than an emergency ligature.
Massive oral haemorrhages
They occur when a tumour of the base of the tongue erodes the small branches of the external carotid artery.They require the ligature of one or both external carotid arteries with the constant necessity to maintain the airways free for breathing.
Occasionally, as in internal carotid rupture, massive oral haemorrhage is a terminal event. Patient sedation should be very quickly administered in order to avoid suffocation by patient’s own blood.
Epistaxis
Epistaxis (nose bleeding) is very frequent during aplastic chemotherapies especially during leukaemia induction treatment.Epistaxis is rarely life-threatening and spontaneously stops with nose compression or nose packing.
When epistaxis is posterior, it requires posterior packing during pharyngoscopy.
Bleeding from ethmoidal tumours generally requires adequate surgical treatment or embolisation.
Massive haematuria
It is a rare event which occurs:A massive bladder haemorrhage requires the maintenance of a correct urinary circuitry in order to avoid hydronephrosis: fitting of a double tract urinary catheter, bladder washing, hydration, transfusions and cystocopy to confirm diagnosis.
- In massive bladder involvement by a bladder or prostate cancer
- After toxic chemotherapy (alkylating agents such as cyclophosphamide or ifosfamide in relation to their bladder-toxic metabolite acrolein),
- After BCG cystitis for a superficial bladder tumour,
- After post-radiotherapy cystitis (related to the dose delivered to the bladder)
- In case of various severe coagulation disorders.
In relapsing massive badder haemorrhages, laser beam, haemostatic irradiation, hypogastric artery embolisation, hypogastric artery surgical ligature or sometimes haemostatic cystectomy have been proposed.
Femoral artery rupture
It is a rare complication due to the invasion of the femoral artery by a metastatic inguinal node from the penis, vulva or a tumour from an inferior limb.Generally these nodes have been irradiated and suturing the bleeding femoral artery is almost impossible.
Thus, as for carotid artery ruptures, clear measures should be taken in order to minimise the dramatic and
traumatic nature of patient death.
Respiratory emergencies :
Acute respiratory insufficiency
In acute respiratory insufficiency, an important fall in arterial oxygen pressure is observed with a major increase of C02 pressure.Clinical symptoms are hypoxia, dyspnoea, tachycardia, peripheral vasoconstriction, agitation, confusion and even obnubilation with cyanosis leading to respiratory distress.
Acute respiratory insufficiency has many causes ranging from mechanical tracheal disorders to alveoli exchange disorders or neurological disorders altering the respiratory mechanism.
A precise evaluation of the mechanisms of respiratory insufficiency is necessary to decide on a potentially efficient treatment.
Among the various aetiologies:
- Pulmonary infection related to cancer or to its therapy (chemotherapy)
- Alveolar pneumonia in relation to bacteria, virus, fungi, after radiotherapy or chemotherapy
- Carcinomatous lymphangitis,
- Swallowing disorders and endobronchial fluid aspiration,
- Multiple embolism,
- Atelectasia in relation to a bronchial tumour,
- Brain metastases or cerebral oedema with compression of respiratory centres,
- Quadriplegia,
- Pneumothorax,
- Metastatic pleural effusion,
- Major opioid intoxication with hypoventilation and hypercapnia,
Acute respiratory distress
A fulminating form of respiratory insufficiency syndrome may occur either spontaneously or after lengthy evolution of existing respiratory insufficiency.It associates a very rapidly developing hypoxia, with diffuse multilobular infiltration at chest x-ray, similar to non-cardiogenic pulmonary oedema, with diminution of pulmonary compliance and arteriovenous shunt.
It is a diffuse alveolar disease and a non-specific lung reaction to major aggression.
Such acute respiratory insufficiency requires patient admission into an intensive care unit.
Its prognosis is very poor: nearly 90% of patients with lung cancer, 40% with breast cancer who are admitted into an intensive care unit for respiratory assistance die in the month following their admission. Such a high mortality rate may question the appropriateness of admission of these patients into intensive care units.
In fact, treatment is symptomatic with high oxygen supply which almost always requires endotracheal intubation, multiple aspirations, and machine-assisted ventilation in order to maintain oxygen saturation over 90%. Other cardiovascular rehabilitation measures and antibiotics are also necessary.
Pleural effusion
Cancer is the most frequent cause of massive pleural effusion which may be complicated by cardiovascular decompensation. Pleuresia is generally a sign of the incurability of lung cancers (however not for lymphoma or other highly chemosensitive cancers).Pleural puncture can be both of diagnostic and therapeutic value with a clear improvement of dyspnoea. It can be complicated by pneumothorax, haemorrhage, empyema or cancer cell sowing along the puncture path.
In the case of frequent or rapid relapse, intrapleural chemotherapy may be proposed (if such chemotherapy is potentially effective) or simple talc pleurodesis which will allow the drying of pleural effusion over a long period of time.
Acute airway obstruction
We can distinguish obstruction of the upper airways (hypopharynx, larynx, trachea down to the carena) and lower airways (bronchial and lower airway).Obstructive lesions are manifested by coughing, dyspnoea, stridor, cyanosis, atelectasia and possibly death.
Upper airway obstruction
Upper airway obstruction constitutes a genuine medical emergency.
They are due either to the intrabronchial aspiration of food or saliva, or to tracheal stenosis, tracheomalacia, oedema or a complication related to treated tumours (in particulare oedema).
Diagnosis is evoked by major inspiration difficulties with intercostal muscle retraction and major psychological distress. Acute transformation may be very rapid: the patient becomes cyanosed, unable to speak and extremely agitated before dying within a few minutes.
The endoscopic examination should be carried out quickly in order to find out the cause of the obstruction and to treat it if possible (removal of a foreign body, aspiration of a mucous mass). Occasionally, rapid tracheotomy needs to be performed.
As soon as the risk of asphyxia has been removed, all necessary measures should be taken to avoid any feared relapse of such acute obstruction.
Lower airway obstruction
It is rarely such an acute phenomenon. It is generally due to bronchial carcinoma or a metastatic endobronchial lesion.
The obstruction usually provokes hemoptysis, dyspnoea and fever with obstructive pneumonia.
Fiber bronchoscopy generally allows the evaluation of the endobronchial lesion and consequently the proposal of appropriate treatment (surgery, radiotherapy, chemotherapy or an association).
A symptomatic treatment may also be proposed (laser, endobronchial brachytherapy, endobronchial stent).
Aspiration pneumonitis
It is a common life-threatening syndrome for aged bedridden people, confused patients or patients suffering from swallowing disorders as well as those fed with naso-gastric tubes in supine position.The risk involved in lung aspiration of a gastric liquid with a low pH, especially for intubated patients or tube fed patients, is the constitution of alveolar lesions associated with super-infection due to aspirated food.
Massive aspiration can provoke death by suffocation.
Most often, after the initial endobronchial aspiration, the patient coughs and ejects most of the inhaled material; however a few hours later, an increasing dyspnoea accompanied by coughing, fever, hypoxemia and pulmonary oedema signifies the onset of an acute respiratory distress syndrome.
Occasionally, the endobronchial inhalation of alimentary liquid remains totally unnoticed and a chronic infection appears a few days later.
Treatment includes respiratory rehabilitation, antibiotics, tracheobronchial aspiration and bronchoscopic washings with physiological fluid.
Metabolic emergencies (1) :
Hypercalcaemia
Hypercalcaemia is a common manifestation among cancer sufferers: 20 – 40 % of multiple myeloma, 35% of lung cancers, 24% of kidney cancers, 8-10% of breast cancer. Hypercalcaemia generally underlines the poor prognosis of cancer, although new therapies may offer longer patient survival.Physiopathological mechanisms
There are two different circumstances, whether osteolytic lesions are present or not.If osteolytic lesions are present, then hypercalcaemia is generally a late phenomenon underlining poor prognosis. Hypercalcaemia induces symptoms that should be corrected with efficient palliative care.
Many hypercalcaemia appear without any osteolytic lesions and are therefore true paraneoplastic syndromes possibly due to several mechanisms:
There is no clear relationship between the presence of bone metastases and the elevation of serum calcium: some diffuse metastases, with major mechanical complications, never produce hypercalcaemia, whereas some very evolutive hypercalcaemia, difficult to reduce, have normal imaging even with gammagraphy and RMI.
- Production of proteins which bind to the parathormone receptor (PTH-like): in the tumour DNA, a gene expresses a polypeptide (PTH-RP or parathormone related protein) with 70% homology with normal parathormone. This gene is normally expressed in mammary tissue during lactation.
- Myeloma tumour cells produce a factor that stimulates osteoclasts (or OAF: Osteoclast Activating factor) which can be produced by in vitro stimulated normal leukocytes. OAF is one member of a larger family of factors called lymphokines, with lymphotoxine (produced by activated lymphocytes) and TNF (tumor necrosis factor or cachectine) produced by normal monocytes. Both factors stimulate osteoclasts.
- Several lymphoma, bone tumours or sarcoma can induce hypercalcaemia by transforming normal 25-hydroxy-vitamine D into 1,25 – dydroxy- vitamine D (the final active metabolite of vitamine D).
Symptoms
The main symptoms of hypercalcaemia are:Diagnosis is made by calcaemic dosage which should systematically be requested in the case of doubt.
- Anorexia, thirst, constipation or even occlusion,
- Consciousness disorders: fatigue, somnolence, lethargy, coma
- More or less intense dehydration, initially extra-cellular then intra-cellular.
Untreated hypercalcaemia leads to severe dehydration and possibly to patient death by cardiac rhythm disorders.
Biological diagnosis
Malignant hypercalcaemia is easy to distinguish from other forms of hypercalcaemia: generally blood phosphorus is normal or elevated (as opposed to hyperparathyroidism).Treatment
Several treatment modalities have been proposed depending on the clinical severity of hypercalcaemia.However, diphosphonates (in particular intravenous forms) have totally modified such modalities allowing ambulatory treatment over several weeks, with prolonged survival and good quality of life.
The only major point to ensure is correct patient rehydration, if necessary intravenously. Corticosteroids are still useful if hypercalcaemia is very high.
Metabolic emergencies (2):
Hyponatraemia
Cancer patients frequently suffer from hyponatraemia, the physiopathology of which is not always clearly understood. Generally, it is fortuitously discovered on a systematic ionogram. However, hyponatraemia increases patient fatigue and can possibly be complicated by somnolence or seizures.Hyponatraemia is often observed in preterminal stages of severe disease. Patients excrete the sodium excesses administered in order to correct hyponatraemia and liquid restriction leads to more severe dehydration than that already observed. Surprisingly, if patients are able to resume normal eating, a spontaneous correction of hyponatraemia is observed.
Thus, this preterminal hyponatraemia should be distinguished from an inappropriate secretion of ADH which is a genuine paraneoplastic syndrome (occurring in lung cancer for instance). Hyponatraemia leads to severe neurological disorders and to an exaggerated water excretion by the kidney (excessive urinary osmolality). In such cases, fluid restriction is useful, but more particularly the treatment of cancer, where possible, will improve the clinical situation.
Another frequent cause of hyponatraemia in cancer patients is the presence of oedema leading to a dilution syndrome. Such a clinical situation can be observed when ascitis or major pleural effusion occur. Whereas symptomatic treatment (ascitic puncture, diuretics) may be useful, only aetiological treatment will actually correct hyponatraemia for a reasonably long time.
Tumour lysis syndrome
The term tumour lysis syndrome covers the quick appearance in blood of intra-cellular products (nuclear acid metabolites) after the death of a great number of cancer cells due to efficient chemotherapy.This syndrome is observed for cancers with very quick tumour growth, important cellular turnover, important tumour burden and great sensitivity to chemotherapy (or radiotherapy) such as leukaemia, high grade lymphoma, small cell lung carcinoma or myeloma.
Uric acid is the final degradation product of purinic nucleic acid: in urine, the acidity transforms the sodium form into uric acid which is not very soluble at this pH level. Crystals appear and provoke an obstructive nephropathy and, secondarily, renal insufficiency. In the case of massive cellular necrosis induced by chemotherapy, we can also observe hyperkaliaemia and hyperphosphataemia with hypocalcaemia, thus involving a risk of cardiac arrhythmia and sudden death.
The urological syndrome generally appears two days after chemotherapy.
Treatment includes massive hydration but more importantly prevention by systematic prophylactic administration of allopurinol a few days before the beginning of chemotherapy. This drug blocks xanthine oxydase and inhibits the formation of uric acid. Another important point is to alkalinise urines and obtain major diuresis through infusion before chemotherapy (at least three litres per day).
Infections and cancer :
Infections are one of the main problems in haematology: around 80% of patients with acute leukaemia, 75% of patients with lymphoma and 50% of those with myeloma will, at some stage, contract severe infection. In solid tissue oncology, infections are less frequent, with the exception of cases of intensive treatment or during the pre-palliative phase.
Main factors involved in increased infection risk
Many factors are implied in this increased infection risk:Neutropenia
Neutropenia is almost always induced by anti-cancer therapy, in particular chemotherapy. In order to obtain maximal efficiency, the dosage of modern chemotherapy (even in an adjuvant setting) is calculated in order to be just under the risk of febrile neutropenia, so that approximately 80 to 90% of the patients can be treated without severe neutropenia. Of course, since this is a statistical gamble, around 10 to 20% of patients will suffer, at least once after one course of chemotherapy, from febrile neutropenia or possibly an infectious episode.The infectious risk is only increased when neutropenia falls under 1,000 per mm3, however it becomes very serious under 500 polymorphonuclears (PMN) per mm3 and almost constant when PMN counts are under 100 per mm3. The intensity of nadir (the lowest point on the curve), is far less important for infectious risk than the duration of this nadir. After a few days with a PMN level below 100 per mm3, the infectious risk is almost constant and requires preventive isolation measures.
Occasionally, patients suffer no severe neutropenia but an alteration of their phagocyte functions in relation to chemotherapy, resulting in the same effect.
Neutropenic patients do not express infections in the same manner as patients with normal leukocyte counts: they cannot produce pus or inflammation. For instance, they may have a severe lung infection, without purulent expectoration, but rather rapid respiratory insufficiency with pulmonary lesions which can very quickly become irreversible (necrosis without PMN reaction).
In a similar manner, they do not have pus in their urine but only bacteria. They do not harbour abscesses but necrosing lesions.
The most frequent sites of infection for these patients are: the throat, the lung, the urine, the skin and the perineal regions, and most infectious germs are those generally present in the patient’s body. Preventive measures are therefore most useful, in particular careful body washing.
Cellular immune dysfunction
Certain cancers, but to a greater extent, certain chemotherapies can lead to the severe depression of cellular immunity. Hence, since T lymphocytes and monocytes cannot be activated, numerous infectious factors will develop.Among them, those expressed within the cell are the most fearsome.
For instance, bacterial infections with mycobacteria, listeria, nocardia, legionella, but also fungi infections with cryptoccoques, histoplasma, pneumocystis carinii, toxoplasmosis, or viral infections by cytomegalovirus or herpes simplex virus.
Humoral immune dysfunction
These disorders are mainly observed in haematological syndromes (myeloma, Waldenström’s disease). Hypogammaglobulinaemia or specific deficiencies in producing antibodies do not allow the humoral immune response and the adherence of germs through antibodies.The difficulty in performing vaccinations during chemotherapy is also noteworthy.
Local factors
Local mechanical factors induced by tumours may be responsible for the breach of natural anatomical barriers (for instance: local skin invasion, digestive tract invasion, respiratory airway invasion).The obstruction of respiratory airways or digestive tracts also leads to a slowing of normal excreta flow (bronchial retention, intestinal occlusion).
The aggression of digestive or respiratory mucosae by chemotherapy (or radiotherapy) also promotes local super infection.
Intra-corporeal foreign bodies
The presence of intravenous catheters, urinary catheters, tracheostomy, ureterostomy is an open door to germs. Prevention of infection during the fitting of intravenous catheters or devices requires rigorous surgical asepsis, high quality post-surgical care as well as surgical asepsis during the use of these devices, with, if possible, a delay between fitting and first use allowing sufficient healing time.Study of the main 'cancer' infections
Only a few infections, frequently observed among cancer patients, will be revised here:bacterial infections,
fungal infections,
viral infections,
parasitic infections.
Bacterial infections:
The spectrum of bacterial infections is changing following modifications in hospital eco-systems, in reaction to antibiotic prescriptions.
The following table shows the recent evolution of bacterial infections:
Type of infection | ||
Bacteriologically documented infection | 30% | |
| 50% | |
| 32% | |
| 16% | |
| 2% | |
Clinically documented infection | 20% | |
Fever of unknown origin | 50% | |
TOTAL | 100% |
This table shows that 20% of clinically documented infection could not be bacteriologically documented. For 50% of observed fevers, we have no clinical or bacteriological proof of infection.
Main identified bacteria
Pseudomonas aeruginosa (ou pyocyanic bacillus)
Even if the modern and new antibiotics can almost always control this infection, pseudomonas remains one of the most feared bacteria in oncology.
The most dangerous form is pulmonary infection with a diffuse infiltrate, dyspnoea, coughing and a risk of toxic shock.
However, pseudomonas aeruginosa is also found in urine, skin infections, central venous catheter infection or perinea infections where gangrenous forms are the most arresting.
It is one of the most important hospital germs which resides in all humid zones and is transported by carers from one patient to another, hence the importance of hygiene procedures.
This is a gram negative bacillus, frequently present in hospitals. It is often present on central catheters and pulmonary infections are the most common site, although many other infections have also been described. The same risk of toxic shock exists as with other gram negative bacilli.Being one of the most dangerous nosocomial germs, it is regularly monitored by health authorities controlling hospitals.
Xanthoma maltophilia
This microbe family is among the most widespread opportunistic bacteria. Present everywhere in nature, it is present in damaged tissue or central catheters in immunodepressed patients. Almost every organ can be the site of infection, but septic shock is relatively rare. This bacteria would appear to become resistant to usual antibiotics.Acinebacter
Salmonella may induce classical gastro-intestinal disease like typhoid fever, however in immunodepressed patients (such as cancer patients on chemotherapy), other sites have been observed such as the lung, urine, peritoneal infections, meningitis or osteomyelitis. This bacterium has become resistant to classical chloramphenicol and requires new fluoroquinolones or cephalosporins.Salmonella
These bacteria are still highly pathogenetic in oncology. They usually provoke pneumonia or septicaemia with possible rapid lethal evolution. Recently, streptococci have become resistant to standard antibiotics and require a precise antibiogram adjustment.Streptococci
Certain strains (such as streptococcus viridans or streptococcus beta-haemolytic) may lead to severe septicaemia, with a risk of shock and secondary localised infections resistant to classical penicillin-based drugs.
These bacteria are usually situated on the skin and contaminate the patient after a surgical procedure or an invasive procedure performed with doubtful asepsis. However, often no precise cause is found to explain staphylococcal septicaemia.Staphylococci
A precise antibiogram is also necessary to correctly adjust antibiotics.
Often related to an alimentary contamination (such as fresh cheese or milk), the listeria infection is dangerous in immunodepressed patients, involoving septicaemia, meningitis, encephalitis or endocarditis. The identification of the bacteria can sometimes prove to be difficult. Most strains are sensitive to ampicillin and other classical antibiotics.Listeria
Bacteria identification
Direct microscopic examination of specimens, with Gram and Ziehl colorations, is always requested. Such examination may offer positive results thus allowing immediate treatment.
Most culture techniques give results in 24 hours (usual media) to 48 hours (specific media).Techniques identifying bacterial antigens or bacterial DNA allows the shortening of this identification delay to a few hours if necessary.
Fungi Infections :
Fungi infections are complications that are most frequently observed among immunodepressed patients (either after haematological cancer or after an intense chemotherapy regimen or during the preterminal phase).
We can distinguish:
- Classical fungi infections which can occur in healthy subjects (including cryptococcosis or histoplasmosis).
- Opportunistic infections which are very rare in healthy subjects (including aspergillosis or systemic candidosis),
Candidiasis
Candida albicans is one of the most frequent fungal infections in oncology. Two factors explain its development:
The sites of external infection are numerous: mouth, oesophagus, urine, genital tract with painful symptoms in each location.
- The immune depression consecutive to chemotherapy (or radiotherapy),
- The large use of antibiotics which select this mycosis.
Systemic candidiasis is manifested by pulmonary lesions, urinary or renal lesions, other atypical lesions (liver, spleen, articulation, eye, meninx, heart). This generalised infection has no specific characteristics.
The systematic research for candida albicans enables its discovery: blood culture, serological reactions are not always significant. Enolase detection by the ELISA technique appears promising.
Often clinicians should decide to treat a patient presenting with fever resistant to antibiotics and persistent neutropenia.
Treatment may be difficult. Many strains are now resistant to fluconazole and an association of amphotericin B with flucytosine may be necessary despite their iatrogenic risks.
Aspergillosis
Aspergillosis is becoming more and more frequent in immunodepressed patients treated by chemotherapy and simultaneously treated by high dose corticosteroids (particularly in haematology). Aspergillus fumigatus remains the most common strain.
Generally, Aspergillus fumigatus provokes a pulmonary lesion such as necrosing bronchopneumonia, with hemoptysis, solitary lung abscess or miliary lesions.
Diagnosis is evoked by chest x-ray or scanner and confirmed either by sputum analysis (or after bronchial aspiration) or by aspergillus antigen serology using the ELISA technique.
General dissemination is possible, potentially involving all organs, and includes venous thrombosis and multiple central neurological involvements.
Treatment is difficult, using amphotericin, possibly in liposomial form, or itraconazole. Treatment of residual sterile lung cavity may require secondary surgical excision.
In immunodepressed patients, preventive isolation avoids the majority of contaminations.
Cryptococcosis
Cryptococcus neoformans essentially infects immunodepressed subjects, but is generally acquired before hospitalisation.
The most frequent pathology involves isolated pulmonary lesions with no symptoms except permanent fever. Pulmonary images are not specific and diagnosis requires the isolation of yeast cells either on bronchial sputum or on alveolar washing.
The disseminated form may be severe with meningo-encephalitis, involving headache, confusion, very disparate neurological symptoms and intracranial hypertension. Radiological examinations are not conclusive. Diagnosis may be evoked through research for circulating antigens (latex test).
A particular form is cryptococcome (or cerebral pseudo-tumour).
Lastly, diffuse skin lesions (ulcerating nodules) and diffuse parenchymatous lesions (bone, kidney, prostate, liver) have been described.
Treatment involves amphotericin, flucytosin and fluconazole.
Histoplasmosis
Histoplasma capsulatum generally provokes benign pulmonary disease. In immunodepressed subjects, disseminated forms may be observed, involving every organ and, in particular, the skin.
The diagnosis is made by direct isolation of the fungi or by immunodiffusion or specific immunoelectrophoresis.
Although most healthy persons do not require treatment, immunodepressed patients will require amphotericin or itraconazole.
Viral infections :
Viral infections are frequent during anti-cancer treatment and in immunodepressed subjects. Sometimes previous viral infections may reappear.
Herpes simplex
Even in healthy people, the herpes simplex virus provokes numerous infections. In immunodepressed patients, these infections may become very severe (after chemotherapy or a medullar graft).
The usual locations (mouth, gum, lips, genital and perianal parts or any other skin region) may become much larger, painful pr even haemorrhagic (if simultaneous thrombocytopaenia exists) and can also involve the digestive tract (oesophagus).
Ocular forms (keratitis) are frequent.
Other locations include encephalitis with necrosis (diffuse lesions, temporal lesions).
Diagnosis is made on clinical examination.
Treatment is based on acyclovir either in local preparations or by general intravenous infusion.
Herpes zoster
During antimitotic treatment, herpes zoster frequently appears, with a typical burning pain situated on the hemi-belt or along a nervous path, followed a few days later by vesicle eruption on a localised dermatoma.
It generally heals with no major problem, but may be complicated by local moderate haemorrhages and more rarely by local necrosis. Post-zoster neurological pains are frequent.
Herpes zoster infection should lead to the stopping of chemotherapy.
Otherwise generalised forms have been described, with visceral, hepatic, adrenal, lung and brain lesions.
Diagnosis is made on clinical examination.
Treatment by acyclovir should be administered as early as possible in order to avoid post-zoster pains which are difficult to relieve.
Cytomegalovirus
Infection generally involves the lung, liver and digestive tract.
Pulmonary and hepatic lesions can be severe.
Diagnosis is based on specific serologic examinations.
Treatment includes ganciclovir and foscarnet.
Respiratory syncitial virus
This viral infection is a community acquired or nosocomial pneumonia.
The respiratory symptoms are acute: fever, coughing, sinusitis, interstitial pneumonia which can lead to rapid pulmonary insufficiency.
This infection is generally seen in profoundly immunodepressed patients.
Treatment with ribavirine should rapidly be instituted.
Progressive multifocal leukoencephalopathy
This is a rare disease probably related to a slow papova virus which is most often observed in AIDS patients but sometimes in severely immunodepressed patients with leukaemia or lymphoma.
The neurological deterioration, due to progressive demyelination is rapid, involving ataxia, blindness and various paresis, progressing towards death within 3 to 4 months.
A few therapeutic successes have been reported with cytosine arabinoside therapy.
Hepatitis
Hepatitis is frequent in oncology and most often related to blood transfusions (hence explaining the interest of growth factors such as erythropoietin).
All forms of hepatitis can be observed (A, B and C).
Fulminans hepatitis with hepatic failure is rare.
Hepatitis (especially hepatitis C) may develop spontaneously in chronic infection, cirrhosis and hepatocellular carcinoma.
Parasitic infections :
In this chapter, we will only discuss opportunistic parasitic infections which can be observed in our country and not those observed in subjects residing in countries harbouring endemic parasitic infections.
Pneumocystis carinii
Pneumocystis carinii provokes pneumonia generally related to reactivation of latent infection but occasionally representing acquired infection. It is observed in immunodepressed patients (such as AIDS sufferers or after intensive chemotherapy).
The clinical onset is insidious: coughing, progressively severe dyspnoea, cyanosis.
Clinical examination is non significant and radiological x-ray pictures are non specific (interstitial diffuse reticular images).
Some authors propose a Gallium gammagraphy. Diagnosis is made by alveolar washings during bronchoscopy or pulmonary biopsy.
Treatment is difficult and involves pentamidine, and an association of sulfamethoxazole-trimethroprime and atovaquone.
Toxoplasmosis
This is a rare complication seen in immunodepressed patients after intensive chemotherapy or during Hodgkin’s disease.
Neurological involvement includes meningoencephalitis with confusion, headache, vomiting, seizures and various pareses.
Cerebral CT scan is normal. RMI scan shows disperse zones of demyelination.
Diagnosis is based on serologic findings (specific IgM by ELISA technique).
Treatment involves various drugs: pyrimethamine, sulfadiazine, cotrimoxazole and spiramycine.
