Extravasation is leakage of intravenous drugs from a vein into the surrounding tissue.
Presentation
Extravasation may present during the administration of chemotherapy or later, with pain and swelling at the site • Th e typical biochemical picture is
of hyperuricaemia, hyperkalaemia,
hyperphosphataemia, hypocalcaemia, lactic acidosis and renal failure.
Prevention
• Early diagnosis requires a high level of
suspicion. In patients at particular risk, routine uric acid and electrolyte measurements are sensible. Correct any pre-existing electrolyte abnormalities.
• Hydrate the patient with at least 3 L of normal saline per 24 hours to maintain urine output greater than 100 mL per hour with or without a loop diuretic to maintain urate clearance. • Give oral sodium bicarbonate to alkalise the
urine and prevent urate nephropathy in acidic conditions.
• If low-risk, give allopurinol 100 mg/m 2 every 8
hours to prevent hyperuricaemia.
• If high-risk (pre-existing hyperuricemia or renal impairment, high tumour burden, high sensitivity to chemotherapy), give rasburicase 200 μg/kg o.d.
• Unfortunately, despite these treatments, 14% of patients will still develop renal problems (Bessmertny et al. , 2005 ).
Treatment
• Aggressive hydration is required.
• Th erapy for hyperkalaemia includes cation exchange resins binding potassium (sodium polystyrene sulphonate), calcium gluconate, sodium bicarbonate to correct acidosis and dextrose/insulin injection.
• Th erapy for hyperphosphataemia and
hypocalcaemia involves oral phosphate binders (aluminium hydroxide 30 mL q.d.s.) and calcium gluconate (10 mL i.v. injection).
• Th erapy for hyperuricaemia involves sodium bicarbonate to maintain urine pH > 7.0 and allopurinol 600–800 mg/day.
• When severe TLS develops, intensive care support and continuous monitoring are necessary. • Renal dialysis is required if hyperphosphataemia,
symptomatic hypocalcaemia, persistent hyperkalaemia, hyperuricaemia and anuria/ oligouria, acidosis or volume overload develops.
Table 8.5 Cytotoxic agents classifi ed according to the type of reaction they typically produce
Class of
drug Defi nition Examples
Vesicant Capable of causing pain, infl ammation, blistering, necrosis Anthracyclines Vinca alkaloids Paclitaxel Streptozocin Mechlorethamine Oxaliplatin Mitomycin Irritant Capable of causing irritation and infl ammation
Platinum compounds Etoposide Irinotecan Topotecan Flurouracil Non-irritant Non-irritant Cyclophosphamide
Ifosfamide Bleomycin Fludarabine Gemcitabine Methotrexate
8: Acute oncology 1: oncological emergencies
Treatment
Experience from case reports and small series has resulted in the publication of guidelines for the pre- vention and treatment of extravasation (Goolsby and Lombardo, 2006 ). Th ere are some general principles for the management of extravasation, together with specifi c measures for each chemotherapy drug. Initial management should include the following.
• Stop infusion, disconnect tubing, but leave i.v. cannula in situ .
• Attempt aspiration of vesicant and administer antidote (see Table 8.7 ) if appropriate. • Keep limb elevated with either cold or warm
compression as indicated (see Table 8.7 for examples).
• Ensure adequate analgesia is provided. • Provide full documentation and monitoring
(consider using a photograph record). • Estimate the amount of extravasated drug. • Consider immediate surgical opinion in cases
of extravasation of a vesicant drug or when conservative treatment fails to improve symptoms or tissue damage occurs.
• Arrange appropriate follow up: telephone contact or day case review .
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Table 8.6 Risk factors for extravasation
Factor Description
Vein physiology Fragile, small, sclerosed Pharmacological Duration and chemotherapy
dosage exposure to tissue Physiological SVCO, lymphoedema,
peripheral neuropathy, phlebitis
Radiotherapeutic Previous local radiotherapy, radiation recall reactions Mechanical Needle insertion technique,
multiple venepuncture sites
Adapted from Goolsby and Lombardo ( 2006 ).
Table 8.7 Antidotes for extravasation
Drug Antidote/treatment
Anthracyclines Topical DMSO 50% Topical hydrocortisone cream 1%
Cold compress Mitomycin As for anthracyclines Vinca alkaloids Infi ltrate the site with
hyaluronidase (1500 units of hyaluronidase in 1 mL of water for injection) using 0.2 mL injections over and around the aff ected area
Warm compress Topical NSAID cream Platins and
Taxanes
Infi ltrate site with hyaluronidase Warm compression
Anti-metabolites Topical hydrocortisone cream Cold compress
DMSO, dimethyl sulfoxide. For more details see Allwood and Stanley ( 2002 ).
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Chapter
in the last 20 years and most of this decrease is likely to be due to improved detection of the primary site using techniques such as histopathology, immunohis- tochemistry and cross-sectional imaging, which have resulted in patients not being registered as having can- cer of unknown primary.
Hospital Episode Statistics (HES) data for England (06–07) recorded a total of 25,318 episodes of care for patients with a diagnosis of cancer of unknown primary representing 308,359 NHS bed-days. Th e majority of patients were fi rst admitted as an emergency.
Deaths from CUP account for 7% of all cancer deaths ( http://www.cancerresearchuk.org/cancer- info/cancerstats/ , accessed December 2014). However, in the absence of a standard defi nition, the true rate may be underestimated.
Th e median age at diagnosis is 65–70 years, but patients presenting with a midline distribution of poorly diff erentiated carcinoma have a median age of 39 years (Casciato, 2006 ; and Kramer et al ., 2008 ).
In patients whose primary site is subsequently identifi ed, the commonest primary sites are the pan- creas (20–26%), lung (17–23%), liver (3–11%), large bowel (4–10%), stomach (3–8%), kidney (4–6%), ovary (3–4%), prostate (3–4%) and breast (2%) (Kramer et al ., 2008 ).
It is important to consider the possibility of poten- tially curable malignancies, such as germ cell tumours or lymphoma, and the investigation of patients with cancer of unknown primary is therefore likely to include biopsy with immunohistochemistry to identify the cell lineage, if possible. Investigations are determined by the site of cancer, the patient’s symptoms, and the general condition of the patient; however, an exhaus- tive diagnostic work-up is not usually justifi ed because it is unlikely to infl uence the outcome of treatment.
Introduction
Cancer of unknown primary origin is a condition in which a patient has metastatic tumour without an identifi ed primary source (NICE, 2010 ). Cancer of unknown primary is an imprecise term, and it is oft en applied to patients in whom limited investi- gations have been performed. To clarify this, NICE clinical guideline CG104 has used the terms ‘meta- static malignancy of uncertain origin’ (MUO), ‘provi- sional carcinoma of unknown primary’ (provisional CUP) and ‘confi rmed carcinoma of unknown pri- mary (confi rmed CUP)’ as summarised in Table 9.1 (NICE, 2010 ).
For those patients whose primary tumour is iden- tifi ed, treatment should continue as for that individual tumour site. But if a primary tumour is not identi- fi ed aft er the initial investigation, treatment has to be empirical and based on research in patients whose pri- mary tumour is known. Th is chapter focuses on the investigation of patients presenting with malignancy of unidentifi ed primary origin (MUO) and the treat- ment possibilities for those whose primary tumour is not identifi ed aft er initial investigation.