OHO-33(583-590) 11/18/02 9:30 AM Page 588 BONE MARROW SUPPRESSION 588 Management of fever in a neutropenic patient Fever is common in patients with cancer. Although commonly caused by infection it can also be related to underlying malignancy, blood product transfusion, and pyrogenic medications. Careful evaluation of fever in a neutropenic patient should not take long. Untreated sep- s is in a neutropenic patient can be rapidly fatal. Generally, antibiotics are administered a fter the following simple investigations: (cid:2) Blood cultures (peripheral and central, i f line in situ) (cid:2) Sputum culture (cid:2) Urine analysis and culture (cid:2) Chest X-r ay (cid:2) Swabs from Hickman line exit site (cid:2) Careful physical examination Treatment should then be instituted, with empirical antibiotic therapy, particularly if the patient is toxic or haemodynamically compromised. The widespread adoption of this approach has redu ced the mortality of neutropenic sepsis to less than 10%. Careful observation of the febrile response to antibiotics, coupled with body \202uid cul ture results, will determine adjustment of anti- biotic therapy over the next few days. If the fever is unremitting at 48 hours, or there is any clinical deterioration, an empirical change of antibiotics to a second-line antibiotic regime should be performed. Failure to resolve the fever within 5 days may suggest other oppor- tunistic infections suc h as fungi or parasites such as Pneumocystis carinii. Careful consideration of these diagno ses, in close consultation with a microbiologist, is required before initiation of speci \201c treat- ments, such as amphotericin B, for these infections, since the therapies thems elves are potentially toxic. Often, resolution of neutropenia results in resolution of refractory fever. This process ca n be accelerated by the use of haemopoietic growth factors. OHO-33(583-590) 11/18/02 9:30 AM Page 589 THROMBOCYTOPENIA IN THE CANCER PATIENT 589 Thrombocytopenia in the cancer patient Thrombocytopenia is commonplace in patients receiving cytotoxic chemotherapy. The trigger l evel to transfuse platelets is not always absolute. Spontaneous bleeding is unlikely if pla telets are >20 \227 109/l, but the risk of traumatic bleeding is greater if <40 \227 109/ l. Most clini- cians would transfuse when platelets are <10 \227 109/l. However, if there is active bleeding, many clinicians would transfuse if <50 \227 109/l. Careful consideration of the patient \200\231s vascular status, clotting status, and diseas e risks (e.g. gastric carcinoma) will determine the threshold for transfusion in an individ ual patient. Cross-matching is not required since patients generally receive random, pooled , donor platelets. Some patients may become refractory after repeated transfusions and HLA-matched platelets s hould be used. Four units of fresh platelets, (doubled if platelets greater than three days old), should raise the count to >24 \200\22340 \227 109/l in an adult. Although frequentl y part of the differential diagnosis of refractoriness, HLA allo-immunization is only one o f many causes. Others include the presence of: (cid:2) Anti-platelet antibodies (cid:2) Dis seminated intravascular coagulation (cid:2) Concomitant drugs e.g. septrin (cid:2) Hyperspl enism OHO-33(583-590) 11/18/02 9:30 AM Page 590 BONE MARROW SUPPRESSION 590 Red cell transfusions in cancer patients A low hemoglobin in a patient with cancer is also common and requires careful diagnostic ev aluation. Elimination of obvious causes such as bleeding from a gastrointestinal malignancy are important before repeated red cell transfusions are given. A one-unit blood transfusio n should raise the hemoglobin by approximately 1 g/dl. Transfusion may reduce the platelet count, so platelet transfusion may be required before or after blood transfusion. Red cell transfusion should be based on clinical criteria rather than absolute trigger valu es. The use of erythropoietin to maintain haemo- globin values in patients with cancer, on or off treatment, is unproven. OHO-34(591-598) 11/18/02 9:31 AM Page 591 Chapter 34 Superior vena cava obstruction Etiology 592 Clinical features 593 Differential diagnoses 594 Investigations 595 Treatment 596 Prognosis 597 OHO-34(591-598) 11/18/02 9:31 AM Page 592 SUPERIOR VENA CAVA OBSTRUCTION 592 Etiology The superior vena cava can be obstructed by: (cid:2) External compression (primary tumor or lymph nodes) (cid:2) Thrombus (secondary to compression; also IV catheters) (cid:2) Combin ation of above In cancer patients the commonest cause is external compression by either a p rimary tumor in the right paratracheal region or a second- ary tumor in the paratracheal ly mph nodes. Lung cancer is the commonest tumor to cause superior vena cava obstruction (SVCO), but any tumor spreading to the mediastinal nodes (especially lymphomas) may do so. Other causes inc lude rup- tured thoracic aortic aneurysm and trauma. OHO-34(591-598) 11/18/02 9:31 AM Page 593 CLINICAL FEATURES 593 Clinical features Symptoms: (cid:2) Swelling of the neck, face, and arms, especially in the morning (cid:2) Headache (c id:2) Visual disturbance SVCO itself does not impair respiration but it is commonly asso- ciated with dyspnoea due t o tracheal or bronchial obstruction/ compression Examination: (cid:2) Fixed engorgement of external and internal jugular veins (cid:2) Collateral veins o ver anterior and lateral chest wall (which drain down) (cid:2) Papilloedema (late feature) OHO-34(591-598) 11/18/02 9:31 AM Page 594 SUPERIOR VENA CAVA OBSTRUCTION 594 Differential diagnoses Heart failure dependent oedema. Tamponade Characteristic symptoms/signs and CXR appearances . External jugular vein compression No facial oedema; no collaterals; usually supraclavicul ar fossa nodes. Jugular veins pulsating not \201xed; other cardiac signs; OHO-34(591-598) 11/18/02 9:31 AM Page 595 INVESTIGATIONS 595 Investigations The clinical diagnosis of SVCO is usually obvious and investigation should be aimed at esta blishing the cause, especially if there is no pre- existing diagnosis of malignancy. Unless the patient has very severe and life-threatening symptoms (e.g. associated stridor) treatm ent should not start until a clear diagnosis (including pathology if possi- ble) has been m ade. Chest x-ray usually shows a right paratracheal mass or other indica- tions of lung can cer or mediastinal lymphadenopathy. It is rarely normal. CT thorax is required only if CXR \201ndings are equivocal or if indicat- ed for the normal investigation of the underlying tumor. Venogram is needed if there is no obvious mass causing external com- pression, or i f thrombolysis or stent insertion are planned. FNA cytology samples should be taken from, f or example, cervical lymphadenopathy. Bronchoscopy is essential if the clinical picture and CXR suggest lung cancer and a histopathological diagnosis is not yet obtained. Mediastinal biopsy (mediastinoscopy, mediastinotomy, mini- thoracotomy, or directed-needle biopsy) is essential if a pathological diagnosis has not been established any other way. There is an i ncreased risk of hemorrhage from these procedures in patients with SVCO, but this is small in experienced hands. OHO-34(591-598) 11/18/02 9:31 AM Page 596 SUPERIOR VENA CAVA OBSTRUCTION 596 Treatment In the majority of cases the treatment is that of the underlying cause and it is important to establish a clear diagnosis (including pathology) before starting. It is unusual for the symptoms to be so severe as to require emergency treatment (unless there is coincident tra cheal com- pression) and the gradual development of collateral circulation means that sympt oms often stabilize. (cid:2) Treatment choices for commonest underlying tumors include: \200\224Small cell lung cancer: chemotherapy (unless physical state very poor); radiotherapy (at relapse following chemotherapy). \200\224Non-small cell lung cancer: surgery is very rarely possible because SVCO is usuall y associated with locally advanced tumor; radical radiotherapy may be possible if the tumor is central but local- ized; for most, palliative radiotherapy is appropriate. \200\224Non -Hodgkin \200\231s lymphoma: usually chemotherapy. (cid:2) Corticosteroids are frequently prescribed (e.g. Dexamethasone 4 mg qds) but there i s no good evidence for their ef \201cacy; anti- tumor effect in lymphoma and Hodgkin \200 \231s disease; helpful if the patient has associated stridor. (cid:2) Thrombolysis is increasingly used as a prelude to stenting. Extensive thrombus in t he SVC and tributary veins may lead to persistent or increasing symptoms and signs despite successful tumor treat- ment. Thrombolysis should only be considered after venography and i f other measures are unlikely to be successful. Where thrombus has formed around a Hickman line (often in association with con- tinuous infusion chemotherapy) removal of the line wil l usually lead to resolution of SVCO. (cid:2) Stenting: an expanding metal stent can be maneuvered into the SVC at the point of s tricture. If an interventional cardiologist with experience can provide a rapid service, th is is now treatment of choice for patients with severe symptoms. OHO-34(591-598) 11/18/02 9:31 AM Page 597 PROGNOSIS 597 Prognosis The prognosis is that of the underlying tumor and its staging. SVCO does not per se imply a worse prognosis, even for patients with lung cancer. OHO-34(591-598) 11/18/02 9:31 AM Page 598 This page intentionally left blank OHO-35(599-604) 11/18/02 9:32 AM Page 599 Chapter 35 Raised intracranial pressure Clinical signs 601 Diagnosis 602 Management 603 Treatment 604 OHO-35(599-604) 11/18/02 9:32 AM Page 600 RAISED INTRACRANIAL PRESSURE 600 The rigid bony skull surrounding the brain is resistant to any increase in the volume of it s contents, with any such change readily leading to a rise in intra-cranial pressure and di splacement of structures. Elevated intra-cranial pressure is characterized in its early sta ges by headache and vomiting, often worse in the morning. With increasing pressure there is drowsiness, heralding a more rapid neurological deteriora- tion. Changes in pressure can s ometimes be more gradual with memory loss and behavioral dif \201culties. OHO-35(599-604) 11/18/02 9:32 AM Page 601 CLINICAL SIGNS 601 Clinical signs In addition to any focal neurological de \201cit, clinical signs suggesting a rise in intr acranial pressure include bradycardia, systemic hyperten- sion, and papilloedema. The latte r may be dif \201cult to identify in its early stages and may be suggested by optic nerve head swelling, blurring of disc margins, and loss of the normal retinal venous pulsa- tion. Speci \201c neurological localizing features should be sought \200\224 Parinaud \200\231s syndrome, (paralysis of conjugate upward gaze), for example, is suggestive of a lesion in the pineal region. The three commonest causes of increased intracranial pressure are: (cid:2) A space-occupying lesion (tumor, abscess, haematoma) (cid:2) Hydrocephalus (due to obstruction of cerebrospinal \202uid (CSF) circulation) (cid:2) Benign intra-cranial hypertension It should be remembered that patients with malign ancy are at risk of developing non-malignant space-occupying lesions (abscesses, haematoma) as a consequence of treatment. Of neoplastic brain dis- order processes, approximately 50% are due to secondary metastases, the remainder encompassing the range of primary brain tum ors, of which gliomas are the commonest. Brain tumors can produce a rise in intracranial pressure either through mass effect or by t he production of hydrocephalus. Hydro- cephalus as a consequence of malignancy is seen more commonly in primary brain tumors, notably pineal tumors and medulloblastoma. OHO-35(599-604) 11/18/02 9:32 AM Page 602 RAISED INTRACRANIAL PRESSURE 602 Diagnosis (cid:2) Clinical (cid:2) Contrast-enhanced CT scan \200\224mass effect \200\224ventricular dilatation OHO-35(599-604) 11/18/02 9:32 AM Page 603 MANAGEMENT 603 Management Early management: (cid:2) High-dose steroids \200\224dexamethasone, 16 mg daily IV mannitol (100 ml 20% solution over 1 \200\2232 hours) (cid:2) Further management: (cid:2) Steroids if poor prognosis (cid:2) Palliative whole-brain radio therapy \200\224little evidence of bene \201t (cid:2) Hormone manipulation \200\224breast and prostate cancers If solitary, consider surgical resection (cid:2) OHO-35(599-604) 11/18/02 9:32 AM Page 604 RAISED INTRACRANIAL PRESSURE 604 Treatment Primary CNS tumors presenting with raised intracranial pressure require a tissue diagnosis. Ventricular shunting may be used in patients with hydrocephalus due to lesions situated in areas dif \201cult to access surgically. However, if at all possible histological con \201rmation should be sought, as it has a major bearing on the therapeutic approach. High-grade gliomas may occasionally have a substantial cystic com- ponent that, even in the setting of recurrent disease, may be drained, leading to rapid resolution of elevated intr a-cranial pressure. Patients with malignant meningitis can present with features sug- gesting raised intracrani al pressure and often have associated cranial nerve palsies. This is often an ominous devel opment in epithelial tumors, but may also occur in some primary CNS tumors, espe- cially me dulloblastoma and pineal region tumors; MRI may demon- strate meningeal tumor deposits. The diagnosis can otherwise be con \201rmed by lumbar puncture, seeking malignant cells in th e CSF, although this must be preceded by CT scan to exclude hydrocephalus. OHO-36(605-610) 11/18/02 9:32 AM Page 605 Chapter 36 Stridor Etiology 607 Diagnosis 608 Treatment 609 OHO-36(605-610) 11/18/02 9:32 AM Page 606 STRIDOR 606 Stridor is the term applied to the high pitched musical noise produced by turbulent air \202ow through narrowed upper airways. It is caused by partial obstruction of the airway ei ther in the region of the larynx or inferiorly in the trachea or major bronchi. Because of the anatomy of the larynx, obstruction above or at the level of the vocal cords pro- duces predominantly inspiratory stridor, whereas obstruction in the subglottis or trachea causes biphasic stridor. OHO-36(605-610) 11/18/02 9:32 AM Page 607 etiology 607 Etiology Stridor can be due to benign or malignant causes. Non-malignant causes may include inhaled foreign body, tracheal stenosis (e.g. post- tracheostomy), or bilateral vocal cord palsy (e .g. post-thyroid surgery). Malignant causes may be: Intrinsic Bulky or extensive primary tumors of the upper airway, larynx, hypopharynx, subgl ottis, and trachea. Bronchial tumors arising in a proximal bronchus invading the carina wil l produce similar symptoms. (cid:2) (cid:2) Extrinsic Thyroid tumors, especially anaplastic thyroid car- cinoma; any tumor caus ing mediastinal lymphadenopathy e.g. Hodgkin \200\231s disease, non-Hodgkin \200\231s lymph oma, or metastatic carcinoma. OHO-36(605-610) 11/18/02 9:32 AM Page 608 STRIDOR 608 Diagnosis (cid:2) Clinical (cid:2) Features of underlying malignancy e.g. goiter, clubbing, weight lo ss (cid:2) Chest X-ray \200\224widening of mediastinum (lymphadenopathy) \200\224primary lung cancer Indirect laryngoscopy (mobility of cords) (cid:2) (cid:2) Fibreoptic nasoendoscopy (cid:2) Bronchoscopy \200\224biopsy/cytology (cid:2) CT sc an (cid:2) Mediastinoscopy OHO-36(605-610) 11/18/02 9:32 AM Page 609 TREATMENT 609 Treatment Treatment is dependant upon the underlying cause. However, in most cases of malignant strid or (particularly if severe) high-dose steroids (e.g. dexamethasone 12 \200\22316 mg) should be given in an attempt to reduce peri-tumoural oedema and relieve airway obstruction. The need for supplemental oxygen may be assessed using pulse oximetry. In severe cases of laryn geal obstruction due to an upper airway tumor or anaplastic thyroid carcinoma, emergency tr acheostomy may be required to preserve the airway before appropriate treatment is initiated . Tumor debulking using laser may be helpful in bulky exo- phytic laryngeal tumors before t reatment commences. Treatment of stridor due to mediastinal lymph node compression is dependant on the nature o f the underlying tumor type. Patients with non-small cell lung cancer should receive urgent palliative radio- therapy. There is anecdotal concern that radiotherapy may worsen peri-tu moural oedema initially, and all such patients should receive steroids. Those with small ce ll lung cancer or lymphoid malignancies will usually respond to chemotherapy. There may be little gained in utilizing radiotherapy initially in such patients. However, in urgent circ umstances, with severe respiratory distress, radiotherapy may be initiated in the absence o f histology. In cases of recurrent malignancy affecting the trachea, laser fulgura- tion, endoluminal st enting, or high dose-rate endoluminal brachy- therapy may provide useful palliation. OHO-36(605-610) 11/18/02 9:32 AM Page 610 This page intentionally left blank OHO-37(611-618) 11/18/02 9:32 AM Page 611 Chapter 37 Acute blood loss Assessment 613 Treatment 614 Gynecological hemorrhage 615 Head and neck hemorrhage 616 Gast rointestinal hemorrhage 617 OHO-37(611-618) 11/18/02 9:32 AM Page 612 ACUTE BLOOD LOSS 612 Massive blood loss (haemoptysis) is often a rapidly terminal event in patients with lung ca ncer, usually caused by erosion of major intrathoracic blood vessels by the primary tumor. Other causes include pulmonary or endobronchial metastases. Non-malignant causes, such as p ulmonary embolism or pulmonary infection, should also be considered in a patient suffering from neoplasia. OHO-37(611-618) 11/18/02 9:32 AM Page 613 ASSESSMENT 613 Assessment The \201rst thought should be whether active resuscitation is indicated. For the patient in the terminal phase of illness, adequate sedation may be more appropriate. Should resusci tation be deemed appropriate, an immediate assessment of haemodynamic stability should be m ade and evidence of coagulopathy sought. A low platelet and \201brinogen level with eleva ted \201brinogen degradation products (FDPs) is indica- tive of disseminated intravascula r coagulation. CXR and broncho- scopy will help to localize lesions within the major airway s and pulmonary parenchyma. An assessment of the patient \200\231s general condition and \201tness should be made to dictate the extent of resuscitation that is appropriate. OHO-37(611-618) 11/18/02 9:32 AM Page 614 ACUTE BLOOD LOSS 614 Treatment Adequate volume replacement with crystalloids, followed by blood, should be given. In patie nts with cardio-respiratory impairment, titration against central venous pressure may be ne cessary. Replace- ment of platelets and clotting factors will be needed in some patients. S peci \201c therapy will be dictated by the individual situation. Radiation therapy can be effective in stopping bleeding from most tumor sites. A short fractionated course, such as 20 Gy in \201ve fractions, or even a single fraction of 8 Gy, can be given. Endoscopic brachytherapy can be a useful tool, especially in patients previously treated by radiation. Bleeding can also be treated endo- scopically in accessible sites. Endoscopic s clerotherapy can sometimes be useful for bleeding from larger vessels; smaller vessel bleed ing may respond to laser treatment with the Nd: YAG laser. In severe, recalci- trant cases, bronchial angiography and selective arterial embolization may be necessary. OHO-37(611-618) 11/18/02 9:32 AM Page 615 gynecological hemorrhage 615 Gynecological hemorrhage Primary or recurrent neoplasms of the uterus, cervix, vagina, or vulva may present with rec urrent small bleeds or with massive life- threatening hemorrhage. Haemorrhagic metastases m ay also cause varying degrees of bleeding. Massive hemorrhage may be the terminal event in patients with end-stage disease. Vaginal packing can be a useful holding measure while more de \201nitive treatment is deci ded. Bleeding originating from the uterus or cervix is best treated with brachytherapy. A c entral tube is inserted into the uterine cavity and two ovoids are inserted into the vagina l fornices. The applicators are then loaded with caesium 137. External- beam radiotherapy c an be integrated at a later date if indicated. Vaginal bleeding more commonly arises from haemorrhagic metas- tases. A vaginal tube can be inserted and subsequently loaded with caesium or external-beam radiotherapy can be offered , usually to a dose of 20 Gy in four or \201ve fractions. In severe cases, surgical ligat ion of the branches of the internal iliac artery may be required. OHO-37(611-618) 11/18/02 9:32 AM Page 616 ACUTE BLOOD LOSS 616 Head and neck hemorrhage Bleeding in head and neck cancer can vary from small recurrent bleeds of no haemodynamic im portance to the so-called \200\230carotid blow out \200\231 caused by erosion of the inter nal carotid artery. The latter is fatal in a matter of minutes. A warning \200\230herald b leed \200\231 can sometimes occur prior to such an event. Recurrent small bleeds arise as a result of degradation of small intra-tumoural blood vesse ls. This symptom can sometimes be the presenting complaint. Bleeding can arise from the muc osal surfaces, from skin ulceration, or can be stomal following surgical treatment. Signi \201cant bleeds arise from major vessel erosion (arterial or venous). This can occur in recurrent disease, often following surgery to the neck or in the advanced neglected pri mary. Signi \201cant bleeds from the neck most often arise following malignant in \201ltr ation of major neck vessels by metastatic lymphadenopathy. Treatment Recurrent small bleeds can sometimes be managed by CO2 laser. Only vessels smalle r than 0.5 mm will respond to such treatment. Slightly larger vessels will coagulate in res ponse to Nd: YAG laser treatment. Should active resuscitation be appropriate, volume replac ement with crystalloids and blood will be necessary. Radiation treatment is the mainstay of palliative therapy in these cases: it often stops bl eeding within a matter of days. Occasional patients presenting with haemodynamically signi \201cant hemorrhage may be candidates for more aggressive therapy. Even patients with T3/T 4 lesions can attain a \201ve-year survival rate of up to 25%. OHO-37(611-618) 11/18/02 9:32 AM Page 617 GASTROINTESTINAL hemorrhage 617 Gastrointestinal hemorrhage Acute blood loss in gastrointestinal cancers is less common than chronic bleeding resulting in iron de \201ciency. It can occur as the pre- senting feature or in the terminal phase of illness in the heavily pre- treated patient. Hemorrhage occurs most often from the prima ry tumor or as a result of its local extension. Previous chemotherapy and clotting factor d e \201ciency, in the case of hepatic impairment, may exacerbate bleeding. Endoluminal meta stases are a rare cause of acute blood loss and metastases to the small bowel can occur in malignant melanoma. Presentation may be with haematemesis, melaena, or fresh rectal bleeding, depending on the site of the lesion. Treatment Speci \201c therapy will be dictated by the individual situation. Radiation ther apy can be effective in stopping bleeding from most sites in the GI tract, although mobile organs (stomach or small bowel) are more dif \201cult to irradiate. Occasional patients presenting with an acute GI bleed from a local- ized cancer may be treated surgically. OHO-37(611-618) 11/18/02 9:32 AM Page 618 This page intentionally left blank OHO-38(619-624) 11/18/02 9:33 AM Page 619 Chapter 38 Obstruction Intestinal obstruction 620 Urinary tract obstruction 622 OHO-38(619-624) 11/18/02 9:33 AM Page 620 OBSTRUCTION 620 Intestinal obstruction Etiology Predominantly associated with pelvic cancers and most commonly found in ovarian (6 \200\22342%), cervical (5%), and colonic cancers (10 \200\22330%). Cause is either intra-l uminal disease (more common in colonic cancer) or extra-mural compression. In ovarian and c ervical cancers there are often multiple levels of obstruction. Obstruction in a patient wi th previous cancer may also be due to non-malignant causes (such as adhesions or gross cons tipation). Obstruction may be complete, subacute, or functional; it may be intermittent. Functional ob struction may be caused by a cancer- related or drug-related (vincristine) autonomic neurop athy, by direct involvement of the mesenteric plexus, or through ileus (e.g. due to perfora tion). Presentation (cid:2) Symptoms \200\224nausea, vomiting, colicky pain, constipation, increased bowel sounds (cid:2) Signs \200\224distension, dehydration, splash, bowel sounds variable \200\224gastric outlet obstruction \200\224large volume projectile vomiting \200\224larg e bowel obstruction; faeculent vomiting Investigation Erect and supine plain abdominal views may con \201rm the diagnosis and will show constipation if present. Where the diagnosis is not clear, contrast barium studies ma y be indicated. If surgery is a possibility and there is doubt about the number of levels o f obstruction or the site of the lesion, MRI can be helpful. Appropriate resuscitation will be guided by clinical and biochemical assessment of dehydration and electrolyte disturbanc e. Treatment options First-line therapy is surgical if active treatment is appropriate. Intrav enous \202uids and nasogastric suction are usually instigated but are not normally necess ary if surgery is not an option. The patient may not wish surgery or, due to the extent of disease, surgery may not be appropriate. Laser therapy may be useful to debulk obstructing oesophageal, gastric, and rectal carcinomas. However, this approach requires repeated treat ments. Plastic tubes or expandable metal stents OHO-38(619-624) 11/18/02 9:33 AM Page 621 INTESTINAL OBSTRUCTION 621 can also be considered and are generally of use in oesophageal or oesophago-gastric lesions . Medical management Inoperable intestinal obstruction can be managed medically. This may per mit the patient to be cared for at home. The patient can eat and drink small amounts. Treat ment approaches vary dependent upon whether subacute obstruction or complete obstruction is pre- sent. The aim is to remove the debilitating feeling of nausea and to reduce the frequ ency of vomiting to a level acceptable to the patient. The symptoms to be palliated are nausea, vomiting, pain, and con- stipation. Oral medicatio n is poorly absorbed in gastro-intestinal obstruction and the subcutaneous or rectal route should be used. Pain For colic, an anti-spasmodic \200\224buscopan 80 \200\223120 mg over 24 hours via cont inuous subcutaneous infusion \200\224is usually effective. Avoid pro- kinetic antiemetics ( metoclopramide) if colic a problem. Pain from cancer or metastases usually requires parente ral analgesics (e.g. diamorphine given subcutaneously over 24 hours via a syringe driver, o r transdermal fentanyl). Nausea and vomiting If partial obstruction without colic is present, metoclopramide, 80 \200\223120 mg over 24 hours sc, may stimulate effective bowel motility. This can be combin ed with high-dose dexamethasone, 16 mg/24 hours, to reduce peri-tumor oedema and to also se rve as an antiemetic. As vomiting is controlled, introduce oral laxatives as tolerated. If obstruction is complete or if colic is present, cyclizine, 100 \200\223 150 mg/24 hours sc, is given with buscopan. Haloperidol, 5 \200\22315 mg/ 24 hours, is a suitable alternati ve. Haloperidol, cyclizine, and hyoscine are all miscible with diamorphine in a driver syri nge. Methotrimeprazine is a highly speci \201c 5HT2 antagonist and has inhibitory effects on ot her emetic pathway receptors. It is a useful alternative to the aforementioned antiemetics and is also miscible with diamorphine. If vomiting persists then octreotide, 300 \200\22360 0 mg/ 24 hrs via continuous sc infusion \200\224a somatostatin analog \200\224can be used. This drug is antisecretory and promotes reabsorption of elec- trolytes and, hence, water fr om the bowel. Effectively this decom- presses the dilated bowel. In dif \201cult cases a nasogastric tube should be considered for short- term use. If all else fails to control the vomiting and it is distressing to the patient, then a venting gas trostomy must be considered, taking into account the patient \200\231s prognosis, current c ondition, and, above all, their own wishes. With a gastrostomy in situ, the patient can tak e oral liquids which can be drawn off via the gastrostomy, as needed. OHO-38(619-624) 11/18/02 9:33 AM Page 622 OBSTRUCTION 622 Urinary tract obstruction Etiology The following are the most common causes of urinary obstruction in patients with c ancer: (cid:2) Carcinoma of the prostate or bladder when the urethra or ureteric ori \201ces become occluded (cid:2) Carcinoma of the cervix or other carcinoma involving the pelvis obstructing the lower ureter (cid:2) Para-aortic nodes or retroperitoneal tumor compressing the ureters (cid:2) Transitional cell carcinoma of one or both ureters (cid:2) Fibrosis following surge ry, chemotherapy, or radiotherapy Symptoms The gradual onset of unilateral ureteric obstruction is often asympto- matic, only diagnosed radiographically as hydronephrosis. Acute ureteric obstruction may cause painful spasm or dull aching in the \202ank, and the pain may radiate in the distribution of the L1 nerve root. Bilateral gradual obstruction becomes symptomatic as the serum urea rises a bove 25 mmol/l, ultimately leading to anuria and renal failure, with lethargy, drowsiness, confusion, nausea, and twitching. Investigations Selective use of abdominal ultrasound, IVU (contraindicated in uraemic patie nt), cystoscopy and retrograde ureteric studies, isotope renogram (assesses function of eac h kidney), and CT scan of the abdomen are helpful. CT of the abdomen with IV contrast as a single modality provides most information by de \201ning any extra-ureteric pathology. Treatment options Bladder outlet obstruction causes symptoms of acute urinary reten- tion o r chronic obstruction, with over \202ow incontinence relieved by urethral or suprapubic ca theterization. Palliative transurethral resec- tion of a prostate or bladder tumor may be n ecessary to provide symptomatic relief. Ureteric decompression can be accomplished by: (cid:2) Percutaneous nephrostomy with or without antegrade stenting (cid:2) Cystoscopy and retrograde placement of an internal ureteric stent OHO-38(619-624) 11/18/02 9:33 AM Page 623 URINARY TRACT OBSTRUCTION 623 Percutaneous nephrostomy is a temporary measure, appropriate in the following speci \201c circumstances: (cid:2) Undiagnosed malignant disease (cid:2) Prostatic or cervical primary, with an available treatment modality with reasonable chance of response Patients with advanced cancer can gain symptomatic bene \201t from nephrostomy/ureteric st ent insertion. However, since a nephrostomy drain may remain in situ for several months, it is prone to dislodge- ment, infection, and leakage around the site. Double pigtail ureteri c stents can be inserted in preference to a long-term nephrostomy. Complications of these i nclude transient bacteremia, urosepsis, haem- orrhage, and obstructive encrustations. OHO-38(619-624) 11/18/02 9:33 AM Page 624 This page intentionally left blank OHO-39(625-634) 11/18/02 9:33 AM Page 625 Chapter 39 Biochemical crises Introduction 626 Malignant hypercalcaemia 627 Hyponatraemia 630 Hyperkalaemia 631 Renal tub ular dysfunction 632 Hyperglycaemia and hypoglycaemia 633 Summary 634 OHO-39(625-634) 11/18/02 9:33 AM Page 626 BIOCHEMICAL CRISES 626 Introduction Cancer and its treatment can cause a wide range of metabolic problems: (cid:2) Hypercalcaem ia (cid:2) Hyponatraemia (cid:2) Hyperkalaemia (cid:2) Renal tubular dysfunction (cid:2) Hy perglycaemia (cid:2) Hypoglycaemia The early symptoms of biochemical abnormalities may be s ubtle and easily confused with those of the underlying disease process. However, they undou btedly adversely affect quality of life and, when severe, may be life-threatening and prese nt as an oncological emergency. OHO-39(625-634) 11/18/02 9:33 AM Page 627 MALIGNANT HYPERCALCAEMIA 627 Malignant hypercalcaemia (cid:2) Complicates 5 \200\22310% of all cancers (cid:2) Especially associated with breast, myeloma, and squamous cell carcinoma of lung If \201ltered, calcium load increases \201ve-fold; kidney cannot excr ete and hypercalcaemia occurs (cid:2) (cid:2) Calcium above 3.0 mmol/L leads to dysfunctional GI tract, CNS, and kidneys (cid:2) Effective treatment improves quality of life Pathophysiology Mechanisms involved in the pathogenesis of malignant hyper- calcaemia inclu de increased bone resorption (osteolysis) and systemic release of humoral hypercalcaemic fa ctors, with or without evidence of metastatic bone disease. Local osteolytic hypercalcaemia is attrib- uted to tumor cell production of cytokines, particularly interleukins and tumor necrosis factors (TNF), prostaglandins, and growth factors, which stimulate prostaglandin function, while parathyroid hormone-related peptide (PTHrP) is the best characterized humor al mediator of hypercalcaemia. In some tumors, such as squamous cell cancers, humoral mech- anisms are dominant, while in others, for example multiple myeloma and lymphoma, osteolysis predominates. In breast cance r, both osteo- lysis and humoral mechanisms appear to be important. Dehydration is also an important contributory factor; calcium is a potent diuretic causing salt and water loss. In myeloma, renal impairment may also develop from deposition of Bence \200\223Jones protei ns. Some lymphomas produce active metabolites of vitamin D that increases the intestinal ab sorption of calcium. Clinical features (cid:2) Renal failure (cid:2) Cardiac arhythmias (cid:2) Non-malignant causes \200\224measu re PTH: inappropriately high in hyperparathyroidism, undetectable in malignancy Management The basic principles of management involve rehydration to restore glomerular fun ction and the use of drugs to inhibit osteoclastic bone OHO-39(625-634) 11/18/02 9:33 AM Page 628 BIOCHEMICAL CRISES 628 Table 39.1 Symptoms and signs of hypercalcaemia Symptoms Signs Gastrointestinal Nausea Vomiting Anorexia Constipation Renal Polyuria Dehydration Thirst Uraemia Hypercalciuria Nephrocalcinosis Neurological Lethargy Muscular weakness Drowsiness Stupor Weakness Confusion Disorientation Dysarthria Visual disturbance Diminished re \202exes Pain resorption. Where possible, speci \201c anti-tumor therapy should be instituted. Occasiona lly, the secretion of humoral factors by a primary tumor results in hypercalcaemia, and in such cases the serum level may be corrected by surgical removal of the tumor. Typically how - ever, the malignancy is advanced and treatment is palliative. Absorption of calcium from the gut is usually reduced in patients with malignant hypercalca emia and, except for the rare patient with lymphoma (usually T cell) associated with raised levels of vitamin D metabolites. They should be encouraged to eat what they like, when the y like, irrespective of the food \200\231s calcium content. Immobilization should be avoide d where possible as this may precipitate hyper- calcaemia, since the lack of weight-bearing induces increased osteo- clastic activity while reducing bone formation. Dehydration is an inevitable feature of symptomatic hypercalcaemia and it is essential to r ehydrate with 3 \200\2234 litres of 0.9% normal saline to restore glomerular function and i ncrease urinary excretion of calci- um. Rehydration will relieve many of the symptoms of hy percal- caemia but will rarely achieve total control. Prior to the 1990s, speci \201c treatment of hypercalcaemia relied main- ly on the use of calcitonin and mithramycin as inhibitors of osteoclast action, but these have largely been superceded by bisphosphonates. OHO-39(625-634) 11/18/02 9:33 AM Page 629 MALIGNANT HYPERCALCAEMIA 629 Corticosteroids have been widely used in the treatment of hyper- calcaemia but, except in s teroid-responsive tumors, add little to the response achieved by intravenous rehydration. ( cid:2) Selective inhibitors of osteoclast activity (cid:2) Agent of choice in hypercalcaemi a \200\224pamidronate, clodronate (cid:2) Highly effective (90% normocalcaemia) (cid:2) Usu ally normocalaemic in 3 \200\2237 days (cid:2) Side-effects \200\224transient fever, hypoca lcaemia IV route needed in acute situation (cid:2) (cid:2) Later, oral maintenance therapy. OHO-39(625-634) 11/18/02 9:33 AM Page 630 BIOCHEMICAL CRISES 630 Hyponatraemia A fall in the serum sodium to less than 130 mmol/l is associated with weakness, confusion, headache, drowsiness, and seizures. In cancer, the likely reason for hyponatraemia is the e ctopic tumor production of antidiuretic hormone (ADH). Small cell lung cancer is the most c ommonly associated malignancy, but carcinoid tumors, lymphoma, leukemia, and pancreatic can cers may also be responsible. Cytotoxic drugs used in the treatment of cancer, particularly ifosfamide, vin- cristine, and high-dose cyclophosphamide, may also stimulate ADH producti on. Other causes for hyponatraemia include pneumonia and raised intracranial pressure. Investigation will reveal continued renal excretion of sodium with an inappropriately high urinary sodium concentration, with the uri- nary osmolality exceeding that of the plasma. Treatments include a restricted \202uid intake of around 500 \200\223700 mls per day, dem eclocycline (which inhibits the action of ADH on the renal tubule), and, rarely, for severe life-threatening situations, the slow and closely monitored infusion of hypertonic (3%) sa line. OHO-39(625-634) 11/18/02 9:33 AM Page 631 HYPERKALAEMIA 631 Hyperkalaemia Renal failure is probably the most frequent cause of hyperkalaemia, but in cancer managemen t other causes should be considered. Most important, and usually preventable, is the tumor lysis syndrome that accompanies the rapid breakdown of malignant cells in response to effec tive chemotherapy. Tumor lysis is most likely in the manage- ment of high-grade lymphomas, leukemia, and trophoblastic and germ cell tumors, where the lysis of many millions of cells results in release of intracellular products, notably potassium and phosphate, into the ci rculation, along with urate generated by the breakdown of cellular proteins. Urate crystals may precipitate in the renal tubules causing acute urate nephropathy if appropriate precau tions are not taken. Prevention of tumor lysis is the key to management and patients who are predicted to respon d rapidly to chemotherapy should be vigorously hydrated intravenously, urinary pH should be maintained in the alkaline range by administration of sodium bicarbonate, and urate nephro pathy prevented by pre-treatment of the patient with allopurinol. Severe, and particularly acute, hyperkalaemia may cause cardiac dys- rhythmias and cardiac arrest. Emergency management is required and this should include intravenous rehydration wi th glucose, insulin, and sodium bicarbonate to correct acidosis and drive potassium into th e intracellular space, and intravenous administration of 10% calcium gluconate. In occasion al situations, haemodialysis may be necessary.