Presenting features Mass, pain and obstruction of: \200 \200 \200 \200 \200 \200 \200 \200 bladder; pelvis; nasopharynx; parameningeal; paratestis; extremity; orbit; intrathoracic. Lymph node involvement is common. Distant metastases are rare. Diagnosis and staging \200 Imaging of primary site: \200 Biopsy for histological molecu lar and cytogenetic analysis. Alveolar RMS characterized by the presence of t(2;13) or t(1; 13). CT scan of chest. Bone marrow aspirates and trephines. Isotope bone scan. Lumbar punct ure (parameningeal primaries). CT, or MRI. \200 \200 \200 Treatment \200 Chemotherapy (6 \200\2239 courses) with ifosfamide or cyclophosphamide, actinomycin, vincri stine, anthracyclines. Surgery is reserved for accessible sites (paratesticular, peripheral ) after 3 \200\2236 courses of chemotherapy. Radiotherapy after surgery for residual tumor and alveolar histology. Prognosis Ranges from <10% survival for bony metastatic disease to >90% for excised parates ticular tumors. Favorable features are: \200 \200 \200 \200 Younger age at diagnosis. Botryoid or embryonal histology. Paratesticular or super \201 ci al head and neck sites. Absence of nodal involvement or distant metastases. Off treatment monitoring Imaging of primary tumor site by US or MRI and CXRs to screen for pulmonary metastatic recurrence. Relapse \200 \200 \200 Second-line chemotherapy. Radiotherapy may be employed at sites not previously irradiated. Outcome for relapse and recurrence is poor. 18_McClure_18.indd 672 11/14/2012 3:51:03 PM GERM CELL tumors 673 Germ cell tumors Germ cell tumors (GCTs) comprise a heterogeneous group of neo- plasms, oft en with mixed histology. They arise from primordial germ cells in gonads or, following aber rant germ cell migration, in midline extrago- nadal sites, including sacrococcygeal, medias tinal, or CNS sites. GCTs are rare occurring in 3 \200\2235 per million children <15yrs of age, with peak inci- dence seen in children aged <3yrs. 10% of girls with ovarian GCTs are found to have an underlying intersex state. The nomenclature of GCTs is complicated. Mature teratoma is benign. Immature teratoma may d isseminate locally. Malignant GCTs: \200 germinoma totipotent; teratoma, yolk sac tumor ( YST), choriocarcinoma (CHC), and embryonal carcinoma (EC) represent more differentiated for ms. Secreting tumors (YST, CHC, some immature teratomas, and mixed tumors) characterized by secretion of AFP and/or hCG, which may be used for diagnosis, monitoring of treatment resp onse, and detection of recurrence. \200 \200 (or seminoma, dysgerminoma, depending on site) is Presenting symptoms Site-dependent. Testicular masses are usually painless. Ovarian tumors present as either painful or painless abdominal mass. Metastases are rarely present at diag nosis (lungs, the commonest site, bone, and bone mar- row). Diagnosis and staging \200 \200 \200 B-hCG in serum (and CSF for CNS disease). Measurement of AFP and Imaging of primary: Biopsy of unresectable tumors (unless unsafe) an d/or imaging and markers suf \201 cient to make diagnosis. CT scan of chest and abdomen. B one marrow and isotope bone scan to look for metastases. US, CT, or MRI. \200 Treatment of extracranial tumors \200 Surgery followed by observation for low risk tumors (e.g. mature/ immature teratoma and gon adal stage I). Note: Testicular tumors should be removed via an inguinal approach. Sacrococcygeal teratoma s should be removed together with the coccyx to reduce risk of malignant relapse. Chemother apy is reserved for intermedi- ate and high risk disease. Prognosis Survival >90% for malig nant extracranial GCTs. 18_McClure_18.indd 673 11/14/2012 3:51:03 PM CHAPTER 18 Oncology 674 Primary liver tumors \200 Hepatoblastoma (HBL) is the commonest primary pediatric hepatic tumor (<1% all cancers), wi th 2/3 of cases in the \201 rst year of life. Hepatocellular carcinoma (HCC) an embryonal (undifferentiated) sarcoma of the liver are rare in children. Serum AFP levels are raised in >80% HBL. Treatment \200 \200 Chemotherapy including platinum drugs and anthracyclines for HBL. Good surgical result is c ritical for long-term survival. Liver transplant is indicated if local resection not possib le. Treatment is the similar for HCC, although they are less sensitive to chemotherapy. Emb ryonal sarcoma is usually treated on soft tissue sarcomas protocols. Prognosis Long-term survival for HBL is >70%, even in presence of lung metastases. Survival for HCC is signi \201 cantly lower. 18_McClure_18.indd 674 11/14/2012 3:51:03 PM OTHER RARE tumors 675 Other rare tumors Up to 5% of malignancies in childhood are very rare. They include: \200 \200 Epithelial or adult-type tumors, (e.g. carcinomas and melanoma). Embryonal tumors (e.g. rha bdoid tumors). Malignant melanoma Risk factors include: \200 \200 \200 \200 \200 \200 pre-existing conditions; giant congenital naevi; dysplastic naevus syndrome; xeroderma pigm entosum; albinism; immunosuppressive diseases. Most cases arise on healthy skin and may be related to sun exposure. Surgery is the mainsta y of treatment. Survival around 90% for local disease; 25% for metastatic disease. Rhabdoid tumors \200 \200 Highly aggressive tumors that arise in kidneys or CNS. In the CNS, they appear histological ly similar to PNETs, but sometimes associated with tumors outside the CNS. Treatment includ es surgery, chemotherapy, and radiotherapy. Long- term survival is rare. Phaeochromocytoma Tumors in the adrenal medulla and sympathetic ganglia are usually spo- ra dic, but may be associated with von Hippel \200\223Lindau disease and multiple endocrine ne oplasia types 2a and 2b (see b p.440). They present with en- docrine manifestations, (e.g. hypertension, excessive sweating) or a mass. Less than 10% of phaeochromocytomas are malign ant. Investigations Plasma and urine catecholamine levels are usually raised. Treatment Surgery after -adrenergic antagonists to control sympathetic symptoms. Nasopharyngeal carcinoma The commonest epithelial cancer in children. It is found in teenag ers and associated with antibodies to EBV: \200 \200 B interferon. Treatment involves chemotherapy, radiotherapy, and 770%. Overall survival at 5yrs Other carcinomas These carcinomas are rare. \200 (predominantly the papillary variant and associated with Thyroid exposure to radiation). Ma y present with asymmetrical nodular goiter (see b pp.420 \200\223421). Adrenal carcinoma (s een in young adults with occasional occurrences in older children). May present with precoc ious puberty, inappropriate virilization in females (see b p.480). 18_McClure_18.indd 675 11/14/2012 3:51:03 PM CHAPTER 18 Oncology 676 Langerhans cell histiocytosis Langerhans cell histiocytosis (LCH) is a disorder of unknown cause with a wide range of presentations. It is not a malignant condition, but may behave l ike one in its severest forms. Usually managed by pediatric on- cologists. Langerhans cells are normally found in skin, lymph nodes, and airways. LCH results from mon oclonal proliferation and accumulation of histio- cytes, with the characteristics of Langer hans cells, in skin, bone, pituitary, CNS, lungs, intestines, spleen, or bone marrow. It ma y manifest as single- or multisystem disease. Single-system disease is usually con \201 ne d to bone, occasionally to skin, and seen more in older children. The natural history varie s from spontaneous resolution to repeated recurrence, or death. Note: LCH was previously known as \200\230histiocytosis X \200\231, which was sub- divided into eosinophilic granuloma, Letterer \200\223Siwe disease, and Hand \200\223 Sch ller \200\223Christian disease Incidence Approximately 1 in 200,000 children affected each year. Presentation Depends on site of disease, but may include: \200 \200 Pain or lump associated with isolated bony disease (most common). Skin rash (widespread mac ular \200\223papular or mimicking seborrhoeic dermatitis of the scalp). Discharge from the ear. Diabetes insipidus. Systemic disturbance (fever, malaise, anorexia, and failure to thr ive). \200 \200 Diagnosis Biopsy with con \201 rmation of Birbeck granules (or positivite CD1a or S100 imm unohistochemistry). Diagnosis can be made without biopsy in the presence of characteristic pituitary/hypothalamic abnormality, where biopsy considered too hazardous, or of lytic bone lesions with clinical features suggesting spontaneous resolution. Further investigation Suspected LCH should be fully staged to identify possible multisystem disease. Investigations should include skeletal survey, abdominal ultra- sound, early morn ing urine for osmolality, FBC and \201 lm, coagulation stud- ies, and liver enzymes. Treatment \200 Single system LCH, usually involving bone or skin, frequently resolves spontaneously or fol lowing biopsy/surgical curettage, but may require topical or intralesional steroids in pers istent or recurrent cases. Multisystem LCH, seen mainly in young patients (aged <2yrs), req uires treatment with steroids and chemotherapy (vinblastine, etoposide, or methotrexate). Prognosis >80% survive long-term without signi \201 cant sequelae. Survivors of multisyst em or CNS disease may have lasting disabilities. 18_McClure_18.indd 676 11/14/2012 3:51:03 PM HAEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS 677 Haemophagocytic lymphohistiocytosis A rare condition that may be p (familial haemophagocyti c/eryth- rophagocytic lymphohistiocytosis, FHL or FEL) or s to infection (sHLH). Characteri zed by accumulation of phagocytic mononuclear cells, rather than dendritic or antigen-prese nting cells as seen in LCH. \200 Presenting features: (2 out of 3 cell lines \200\224red cells, white cells, and platelets). Neurological symptoms relating to increased CSF cell counts and protein sometimes seen. Th ere may also be lymphadenopathy, skin rash, jaundice and oedema, and hepatic dysfunction. B iochemistry: raised serum transaminases and ferritin levels. Other investigations to consid er: testing. include fever, splenomegaly, and cytopenia shows raised triglycerides and low \201 brinogen, sometimes include viral, immunological, and genetic Treatment Recovery may be spontaneous in sHLH with resolution of infection, but FHL is fata l without treatment. Steroids, etoposide, IT methotrexate may stabilize the disease. Alloge neic BMT is required for cure. Overall survival is 750%. 18_McClure_18.indd 677 11/14/2012 3:51:03 PM CHAPTER 18 Oncology 678 Chemotherapy May be given as adjuvant treatment (following surgery), or neoadjuvant treatme nt (before surgery). Combinations of drugs used to increase ef \201 cacy, reduce developme nt of resistance, and limit single organ toxicity. Maximizing dose intensity (treatment fre quency) increases ef \201 cacy. \200 vomiting, myelosuppression, alopecia, and Short-term side-effects: mucositis (in \202 ammation of mucous membranes). Long-term effec ts: effects variable and, in general, less than effects of radiotherapy. on organ function (kidneys, gonads, hearing, heart) Antimetabolites Structural analogs of chemicals found in the intermedi- ate steps in the sy nthesis of nucleic acids and proteins. They include: \200 6-thioguanine (6TG), cytarabine (ara-C), 6-mercaptopurine (6MP): \202 udarabine (used in leukemia, NHL). methotrexate (MTX) used in leukemia, NHL, and OS. Side-effects include renal toxicity (MTX), myelosuppression, hepatotoxic- ity, and mucositi s. Anti-tumor antibiotics Originally isolated from bacteria and fungi, they have antibiotic an d anti-tumor activity. They include the following: \200 daunorubicin, doxorubicin, idarubicin, mitoxantrone, Anthracycline: epirubicin used in leukemia, NHL, HL, neuroblastoma, Wilms \200\231, sarcoma . Side-effects \200\224myelotoxicity, alopecia, mucositis, cardiotoxicity. Bleomycin used i n Hodgkin \200\231s disease, GCTs. pulmonary toxicity. Actinomycin D (dactinomycin) used in Wilms \200\231 tumor, soft tissue and ES. Side-effects \200\224myelotoxicity (mild), hepat otoxicity. Side-effects \200\224include Epipodophyllotoxins semi-synthetic analogs of podophyllotoxin. They stabilize normally tran sient DNA \200\223protein complexes by inhibition of topoisomerase I or II: \200 Etoposid e (VP16 ): inhibits topoisomerase II. Used in leukemia, NHL, neuroblastoma, sarcoma, GCTs, CNS tumors, palliative chemotherapy (low dose). Side-effects \200\224include hypotension, m yelotoxicity, alopecia, hepatotoxicity, mucositis, s leukemia. Topotecan, ironotecan inhibi t topoisomerase I. Used in neuroblastoma, sarcoma, and CNS tumors. Vinca alkaloids Bind to tubulin, interfering with mitotic spindle: \200 Vincristine. Used in leukaemias, NHL, Hodgkin \200\231s disease, CNS tumors, Wilms \200\231 , sarcoma. Side-effects include neurotoxicity. Vinblastine. Used in Hodgkin \200\231s disea se, anaplastic large cell lymphoma. Side-effects include myelotoxicity and mucositis. Vinor elbine, new to pediatric practice, causes mild myelosuppression. 18_McClure_18.indd 678 11/14/2012 3:51:03 PM CHEMOTHERAPY 679 Alkylating agents Covalent binding to DNA, to prevent replication and transcription: \200 Cyclophosphamide, ifosfamide: neuroblastoma, high risk Wilms \200\231, CNS tumors. Melphala n, busulphan: Chlorambucil (Hodgkin \200\231s disease) Lomustine (CCNU): used in leukemia, lymphoma, sarcoma, \200 \200 used in neuroblastoma, ES. used in CNS tumors. Side-effects \200\224myelosuppression, alopecia, mucositis, tubular nephropathy (ifos), bla dder toxicity (cyclo), encephalopathy (ifos), late effects on fertil- ity, s leukemia (CCNU ). Platinum compounds Permanent cross-linking of DNA and inhibition of DNA synthesis. Cisplati n, carboplatin. Used in sarcoma, neuroblastoma, CNS tumors. Side-effects \200\224high emetogenicity, nephrotoxicity, ototoxicity, neurotox- icity (mainly cisplatin), myelotoxicity (carboplatin). Other agents \200 Side-effects \200\224 Dacarbazine (DTIC) methylates nucleophilic sites. mucositis, myelotox icity, hepatic dysfunction, local pain, \200\230 \202 u-like \200\231 symptoms). Procarba zine: once activated in vitro. Side-effects \200\224myelotoxicity, reduced fertility. L-asp araginase: malignancies, e.g. ALL. Side-effects \200\224hypersensitivity, coagulopathy, rar ely pancreatitis. Amsacrine: Hydroxyurea: Steroids: as well as symptom control and reductio n of oedema particularly around CNS tumors, have direct anti-tumor effects in hematological malignancies. originally MAOI, but found to be antitumour. Methylates depletes pool of asparagine, needed by some \200 \200 complex with DNA and topoisomerase II. analog of urea; inhibits DNA synthesis. Safe administration of chemotherapy Chemotherapy should only be given by individuals fully trained in the avoidance and management of the complications, working in centers fully equi pped and accredited to support chemotherapy. Route \200 Intravenous: from peripheral access greatest with vinca alkaloids and anthracyclines. IT: u sually for treatment or prophylaxis of CNS disease in leukemia, NHL, and some CNS tumors: s afety arrangements for IT treatment are paramount. central venous access is preferred. Risk of extravasation Dosage Usually calculated according to surface area. Intravenous \202 uid to prevent tumo r lysis syndrome (see b p.684) is required with certain drugs (e.g. ifosfamide, cisplatin, methotrexate). Mesna is given with cyclo- phosphamide and ifosfamide to protect from bladde r in \202 ammation. Monitoring The type and level of monitoring depend on agents used. This may include periphe ral blood cell counts, GFR measurement, echocardio- gram before and between courses of chem otherapy. 18_McClure_18.indd 679 11/14/2012 3:51:03 PM CHAPTER 18 Oncology 680 Stem cell transplant High dose therapy This involves the delivery of myeloablative doses of chemotherapy and/or radiotherapy, followed by rescue with haemopoietic stem cells. The lat ter may be autologous (from patient) or allogeneic (from sibling, unrelated donor, or haplo -identical from parent). Indications for use in treatment of childhood malignancy: \200 Selected high-risk leukemia and relapsed ALL (from allogeneic donor). High risk solid tumor s, including metastatic neuroblastoma, and high risk ES (autologous). Stem cells are harvested from bone marrow or peripheral blood by leu- copheresis following \200\230mobilization \200\231 with granulocyte colony stimulating factor (G-CSF). Conventional BMT is used for allografts. Peripheral blood stem cell transplants (PBSCT) are favored for autografts. This offers advantages including less risk of tumor contamination, more rapid engraftment, less severe infections, avoidance of anesthetic. Conditioning for BMT involves myeloablative radiotherapy or chemotherapy. The aim is to achieve a state of c omplete remission prior to conditioning. Monoclonal antibod- ies are used to suppress immun e function of donor T-lymphocytes against recipient. Outcome Allografts carry greater risk, with approximately 10% procedure-related mortality. Morbidity and mortality from stem cell transplant are due to: \200 \200 \200 \200 \200 graft failure; infection mucositis; veno-occlusive disease of the liver. multi-organ failur e related to the conditioning regimen. s to profound immune suppression; Graft vs host disease (GVHD) GVHD is a particular risk. It may affect any organ system but commonly skin, liver and the gastro-intestinal system. Ciclosporin A or tacrolimus are give n as prophylaxis and steroids, monoclonal antibodies and other immunosuppressants may be em ployed in treatment. 18_McClure_18.indd 680 11/14/2012 3:51:03 PM RADIOTHERAPY 681 Radiotherapy In the use of ionizing radiation to kill cancer cells, dose and fractiona- tio n (number of treatments to deliver a total dose) vary according to the nature of the tumor and tolerance of the tissue. Strategies to increase therapeutic success include: Conformal radiotherapy: sparing surroun ding tissue. Hyperfractionation and acceleration. Targeted radiotherapy with speci \201 c isotopes, e.g. I neuroblastoma, Radiosurgery (high dose single fraction), brachytherapy (di rect application of radionuclides to tumor). Protons (reduced dose to non-target tissues): currently limited availability in pediatrics. matching beam to 3D shape of target and so \200 131MIBG for Indications \200 Selected cases of Hodgkin \200\231s disease, neuroblastoma, Wilms \200\231 tumor, soft tiss ue and ESs, most subgroups of CNS tumors. Limited bene \201 t in OS, extracranial GCTs, NH L. In leukemia limited to treatment of CNS and testicular disease and to conditioning for B MT. Symptom control in palliative care, e.g. bony metastases, spinal cord compression. \200 Preparation for radiotherapy \200 \200 Planning, by combination of CT and MRI scanning. Immobilization using masks/shells, tattoos as markers; sedation or general anesthesia for youngest children. Protection of surroundin g tissues, e.g. gonads, using lead shields. Play therapists have a central role in this pro cess. \200 Side-effects \200 Acute effects include nausea and vomiting, cutaneous erythema and desquamation, diarrhea, m yelosuppression, pneumonitis, hepatitis. Toxicity is potentiated by actinomycin D or anthra cyclines. Late effects on growth, CNS, heart, lungs, kidneys, liver (see b p.688). Surgery Surgical interventions for solid tumors include the following. \200 chemotherapy and/or radiotherapy may be curative Biopsy only: without further surgery, e.g. HL, NHL, RMS, GCTs. Resection, primary or follow ing chemotherapy. Completeness of excision in \202 uences subsequent adjunctive treatment, e.g. bone tumors, Wilms \200\231 tumor, hepatoblastoma, and most CNS tumors. Management of the acute abdomen in neutropenic patients. Raised ICP and spinal cord compression. Tunnele d central venous lines for chemotherapy. \200 \200 18_McClure_18.indd 681 11/14/2012 3:51:03 PM CHAPTER 18 Oncology 682 Acute care All pediatric oncology treatment centers should have clear local guide- lines fo r supportive management, which should be referred to for details. This section should not b e regarded as a substitute for such guidelines. Fever should be treated as an emergency. Im munocompromised children may succumb to overwhelming sepsis within hours. Greatest risk is as- sociated with the nadir white cell count (typically at around 10 days) for most regimen s. In the absence of neutropenia, central venous line infec- tion should be considered, par ticularly if there are symptoms (e.g. rigors) associated with line \202 ushing. Febrile neutropenia Fever (temperature >38 C) with neutrophil count <1.0 \227 109/L, lead ing to increased risk of bacterial infections. Complicates chemotherapy, spinal radiotherap y, bone marrow disease. Causes \200 \200 \200 Skin or GI bacterial \202 ora. Greatest risk from Gram \200\223ve organisms, including G ram-+ve organisms may be associated with central venous catheters. Pseudomonas. Examination Include inspection of the skin, mouth, IV line sites, surgical sites, and the p erianal area. Investigation \200 \200 FBC and differential count, CRP. Culture of blood, urine, stool, swabs of throat, nose, sus picious skin lesions, or central line exit sites. CXR/AXR if indicated by symptoms or signs . Treatment \200 Broad spectrum antibiotics should be commenced infection with Gram \200\223ve bacilli (cid :1) may be fatal within hours. Antibiotic choice will vary by institution and local resista nce patterns, but must include adequate cover for Pseudomonas and Gram-+ve organisms. Inclu de anaerobic cover in the presence of abdominal pain, diarrhea, or mucositis. Appropriate a gents may include: \200 without delay as Ceftazidime, cipro \202 oxacin, meropenem, gentamicin, amikacin, piptazobactam (Gram \200 \223ve cover). Vancomycin, teicoplanin (Gram +ve organisms, including coagulase- negative s taphylococci). Metronidazole, meropenem (anaerobic cover). Antibiotic choice should be reviewed according to results of cultures. 18_McClure_18.indd 682 11/14/2012 3:51:03 PM ACUTE CARE 683 Infection Viral infections in immunocompromised patients \200 VZV: immune globulin. Active chickenpox or shingles should be treated aggressively with IV aciclovir. HSV: if in contact and non-immune, give prophylactic aciclovir or zoster may cause painful oral ulceration; treat early. Other viruses \200 CMV, RSV, and adenovirus may all cause pneumonitis, associated with high morbidity and mort ality, especially in BMT patients. Fungal infections \200 Consider in prolonged febrile neutropenia and treat promptly. Mortality remains high, but r educed with newer therapeutic agents. Clinical spectrum includes pulmonary aspergillosis, h epatic candidiasis, abscess formation. Risk is highest during intensive chemotherapy, such as re-induction for relapsed leukemia and following BMT. Treatment includes \202 uconazol e (limited cover), itraconazole, amphotericin B (liposomal formulation for reduced toxicity ), voriconazole, and caspofungin. Prophylaxis is used in high risk treatment regimens. Pneumocystis pneumonia (PCP) \200 associated with prolonged immunosuppression; Interstitial pneumonitis: presents with tachyp noea, dry cough, low oxygen saturation readings. Prophylaxis (patients on chemotherapy last ing over 6mths): co-trimoxazole, monthly pentamidine nebulizers, or dapsone. high dose co-t rimoxazole, steroids in severe cases. Treatment: 18_McClure_18.indd 683 11/14/2012 3:51:03 PM CHAPTER 18 Oncology 684 Acute care: biochemistry Tumor lysis syndrome This involves lysis of malignant cells on sta rting chemotherapy, releasing intracellular contents, exceeding renal excretory capacity an d physiologi- cal buffering mechanisms. Abnormalities include: \200 \200 \200 \200 Hyperuricaemia. Hyperkalaemia. Hyperphosphataemia and reciprocal hypocalcaemia. Dehydration , leading to risk of acute renal failure. Mainly seen in ALL, NHL (especially B cell), occasionally AML, rarely solid tumors (e.g. ge rm cell, neuroblastoma). May occur spontaneously or be precipitated by single dose of stero ids or chemotherapy. Risk is increased with high white count, bulky disease, pre-existing r enal impairment or in \201 ltration. Management Key is prevention and monitoring. \200 e.g. 2.5% or 5% dextrose in 0.45% saline at 3.0L/m2/ Hyperhydration: day 24h before starting treatment, and continued for least 48hr after treat ment started. Avoid added potassium. Ensure good renal output, with diuretic (furosemide) i f necessary. Allopurinol reduces urate precipitation, use urate oxidase in high risk cases. Hyperkalaemia: resonium, dextrose/insulin, haemo \201 ltration. Hyperphosphataemia/hypoca lcaemia: extreme cases; avoid calcium unless symptomatic (tetany, seizures). \200 may need treatment with salbutamol, calcium increase \202 uids; haemo \201 ltration in Other biochemical disturbances Hypercalcaemia Rarely complicates malignancy (usually dissem inated), e.g. rhabdomyosar- coma. Manage with hyperhydration (normal saline) and frusemide; bispho- sphonates more effective than steroids or calcitonin. Renal toxicity Due to chemotherapy or antibiotics. \200 Cisplatin (glomerular function, M g Mg2+, PO4 Amphotericin B (glomerular toxicity and heavy potassium loss), aminoglycosides, vancomycin. 2+ loss), ifosfamide (tubular losses of 2+, bicarbonate), high dose methotrexate. Particular care needed when any of these drugs used in combination. 18_McClure_18.indd 684 11/14/2012 3:51:03 PM ACUTE CARE: OTHER 685 Acute care: other The acute abdomen Possible causes in the oncology patient include the fol lowing. \200 s to gastritis or ulceration. Risk factors include Gastric hemorrhage: high dose steroids and raised ICP. Pancreatitis: Neutropenic enterocoli tis or typhlitis (Greek typhlon = caecum): bacterial invasion (clostridium, pseudomonas) le ads to in \202 ammation, full thickness infarction and perforation, sepsis, and bleeding. It is associated with leukemia. Symptoms of pain +/ \200\223 fever may be masked by concomi tant steroids (e.g. in ALL induction). The key to management is early, appropriate antibiot ic cover on \201 rst suspicion and early involvement of surgeons. Mortality is high. \200 complicating treatment with steroids or L-asparaginase. Hematological support Blood products should be leucodepleted to reduce viral transmission a nd incidence of reactions. The latter are treated with antihistamine and/or steroid. Irradi ated products should be used to prevent transfusion asso- ciated GVHD around the time of st em cell harvesting, following trans- plant, during treatment with \202 udarabine, and for patients with Hodgkin \200\231s disease. \200 Threshold for blood transfusion: usually a hemoglobin level of 7 or 8g/ dL, but teenagers a re often symptomatic at higher levels. (Caution if high count leukemia, longstanding anemia , or heart failure). should be maintained above 10 \227 109/L if well, 20 \227 109/L if P latelets: febrile or for minor procedure (e.g. LP), 30 \227 109/L if brain tumor, and 50 \227 109/L after signi \201 cant bleed or for major surgery. These thresholds should be ov erridden where there is bleeding. Nausea and vomiting Chemotherapy varies in its emetogenicity: oral antimetabolites and vin- cristine require no prophylaxis; cisplatin and ifosfamide require multiple agents. Aim to prevent severe symptoms. \200 \200 \200 First-line: Second-line: Dexamethasone: tumors. Other agents: cases, nabilone, methotrimepr azine or chlorpromazine can help. domperidone or metoclopramide. ondansetron (5HT antagonist). useful adjunct, but not in ALL/NHL induction or CNS cyclizine useful in children with CNS tumors. In severe 18_McClure_18.indd 685 11/14/2012 3:51:03 PM CHAPTER 18 Oncology 686 Nutrition and mucositis Good nutritional status is essential for recovery, but is compromised by the presence of ma lignancy, direct effects of treatment, and mucositis and infection: \200 A dietitian is central to successful nutrition. Support should include making appetizing me als available at all times, calorie supplementation, treatment of mucositis, and use of par enteral nutrition when enteral route inadequate. Chemotherapy-induced mucositis leads to or al ulceration, pain, and diarrhea. Good mouth care (involving basic oral hygiene and antise ptic mouthwashes) helps prevent some infective complications. Prompt treatment with analges ia allows maintenance of oral intake for as long as possible. 18_McClure_18.indd 686 11/14/2012 3:51:04 PM URGENT CARE 687 Urgent care Emergency treatment needed for acute complication of tumors, e.g.: \200 Leuka emias with high peripheral white blood cell count, leading to hyperviscosity. SVC or airway obstruction caused by mediastinal masses. Raised ICP. Spinal cord compression. \200 \200 Hyperviscosity \200 \200 Risk of sludging of venous blood in cerebral vessels. Associated with very high count ALL ( WBC >200 \227 109/L). Prevention \200 \200 \200 Cautious transfusion. Prompt ALL treatment: h Leucopheresis may relieve symptoms. ydration, urate oxidase, chemotherapy. SVC and upper airway obstruction \200 \200 May present with dyspnoea, chest discomfort, hoarseness, cough. Findings in SVC obstruction : veins on upper chest wall, venous dilatation of optic fundi. plethora, facial swelling, engorgement of Causes \200 SVC obstruction: \200 \200 Airway compromise: \200 \200 \200 \200 upper mediastinal tumors (particularly T cell NHL or ALL); occasionally neuroblastoma. thoracic ES; peripheral PNET; rhabdomyosarcoma; malignant GCT. Management \200 Sedation/anesthesia for diagnostic purposes unsafe in SVC obstruction. Empirical treatment based on imaging and non-invasive investigations may need to be used before biopsy con \201 rmation of diagnosis. Presence of pleural effusion, common in T-cell NHL, exacerbates symptoms but tap may relieve symptoms and provide diagnosis. Spinal cord compression \200 \200 Presentation: Causes: infection, osteomyelitis, abscess). Multidisciplinary input vital: an d biopsy should precede steroids to avoid tumor lysis under anesthetic. Perform other essen tial diagnostic procedures (e.g. LP, BM) under same anesthetic if possible. back pain; gait, sensory, bladder, and bowel disturbance. neuroblastoma, sarcoma, lymphoma, CNS tumors (also urgent MRI and surgical decompression Raised intracranial pressure See b p.653. (cid:1) Neurosurgical emer- gency. High dose dexa methasone pre-operatively. 18_McClure_18.indd 687 11/14/2012 3:51:04 PM CHAPTER 18 Oncology 688 Principles of follow-up Follow-up after completion of treatment is focused on disease recur rence and long-term adverse effects of cancer and its treatment. Monitoring for disease recurrence This involves clinical review, combined with imaging or l aboratory testing to pick up pre-symptomatic recurrence, which may be amenable to fur- ther attempts at curative treatment. For example: \200 \200 \200 \200 \200 CXRs and abdominal US: MRI scans: CNS tumors. Urine VMA and HVA: Serum AFP and hCG: Periphe ral blood counts: Hodgkin \200\231s disease. neuroblastoma. GCTs. leukemia. Monitoring for late effects of treatment This is a growing discipline, since there is now a childhood cancer survivor for every 900 adults. Monitoring is focused on the following. Late effects of radiotherapy May occur months or years after treatment has been completed. Sequelae usually progressive and irreversible, and will depend on sites, dose, mode of trea tment, and age of patient at time of treatment. Growth sequelae \200 \200 \200 Direct effects on epiphyseal plates. Growth hormone de \201 ciency from hypothalamic/pitui tary damage. Muscle damage and avascular necrosis of bone. CNS sequelae \200 \200 \200 Somnolence and tiredness. Hypothalamic and pituitary damage. Intellectual effects: memory. Radiation myelitis. Eyes: commonly reduced numeracy and short-term \200 cataracts, retinal damage. Other organ system sequelae Gonads: infertility/hypogonadism. \200\230Second \200\231 primary malignancies Risk of 4 \200\2236% of occurrence within rad iotherapy \201 eld. Common second malignancies include solid tumors occurring in the \201 eld of radiotherapy, as well as non-melanoma skin cancers. Epithelial tumors predomina te. Late effects of chemotherapy Sequelae depend on age at the time of exposure, drugs and dose s (see b p.678). Well recognized long-term toxicities include: \200 \200 \200 Cardiotoxicity following anthracyclines. Nephrotoxicity following platinum drugs and alkyla ting agents. Pulmonary \201 brosis following bleomycin. 18_McClure_18.indd 688 11/14/2012 3:51:04 PM PRINCIPLES OF FOLLOW-UP 689 \200 \200 Impaired fertility following alkylating agents. Ototoxicity following antibiotics. Second m alignancies related to chemotherapy include and myelodysplastic syndrome associated with to poisomerase II inhibitors and alkylating agents. s leukemia Fertility \200 This is affected by gonadotoxic chemotherapy and by radiotherapy \201 elds that impinge o n the gonads. The younger the patient when treated, the better the prognosis for future fer tility. More spermatic recovery is seen after chemotherapy than radiotherapy. Risk of gonad otrophin de \201 ciency greatest for radiotherapy directed towards suprasellar and nasopha ryngeal tumors, but fertility may be preserved with aid of pulsatile gonadotrophin-releasin g hormone (GnRH) therapy. Quality of survival It is understood that the long-term effects of treatment go beyond the purely physical consequences of treatment and this is an evolving area of clinical research . Cancer survivors (and their family members) are at increased risk of impaired psychosocia l wellbeing. Risk is not clearly as- sociated with a speci \201 c cancer type or treatment and is likely to be multi- factorial in origin. Survivors are also at increased risk for n eeding special education and, as they enter adulthood, unemployment or underemploy- ment. 18_McClure_18.indd 689 11/14/2012 3:51:05 PM CHAPTER 18 Oncology 690 Palliative care Around 30% of children with cancer will die, mostly from progressive di- se ase. Death from complications of treatment is more likely to be swift, with limited opportu nity for preparation. Palliative care is the active total care of patients whose disease is no longer curable. It needs to embrace physical, emotional, social, and spiritual needs of children and their fami- lies. Chemotherapy, radiotherapy, and surgery may still be used f or pallia- tion and control of symptoms. Breaking bad news It is extremely important to be honest with an open approach, avoiding fa lse hope. What to tell the child is always dif \201 cult; many families tend to be over-pr otective. This risks loss of their child \200\231s trust when the truth can no longer be hi dden. Organization of care There are few pediatricians specializing in palliative care: \200 Location: prefer a hospice and a minority the acute hospital ward. A multiprofessional appr oach is required and will vary according to needs and organization of local healthcare. The Association for Children with Life threatening or Terminal Conditions (ACT; www.act.org.uk ) has played a central role in the development of pediatric palliative care as a specialty in the UK. Bereavement support should be considered part of the role of the palliative care team and may be provided by various disciplines within the team, depending on local arrang ements. most children die at home, through family preference; some Symptom control Anticipated symptoms will depend on the diagnosis. Symptom control measures may be pharmacological or non-pharmacological. Aim to cor- rect the underlying cause, e.g. constipation, infection. Good communica- tion and consideration of psychosocial and spirit ual factors will contribute to good control. Pain \200 Oral route is effective for most, until the terminal phase, when SC infusion, often in comb ination with anti-emetics, sedatives, and anticonvulsants may be preferred. The transdermal route is used for some agents. Different agents suit different types of pain, e.g. in \202 ammatory and neuropathic pain, muscle spasm, and raised ICP. Combining different agent s is more effective than escalating dose of one. 18_McClure_18.indd 690 11/14/2012 3:51:05 PM PALLIATIVE CARE 691 World Health Organization (WHO) three step analgesic ladder (see b pp.890, 1018). \200 \200 \200 Step 1: Step 2: Step 3: +/ \200\223 adjuvants. non-opioid +/ \200\223 adjuvants (e.g. paracetamol, NSAID); weak opioid (e.g. codeine) + no n-opioid +/ \200\223 adjuvants; strong opioid (e.g. morphine, fentanyl) + non-opioid Adjuvants are additional drugs used in pain management. They include: \200 analgesics that relieve pain in speci \201 c circumstances, such as gabapentin for neuropa thic pain, anti-spasmodics (hyoscine, glycopyrronium), muscle relaxants (diazepam), cortico steroids, bisphosphonates; drugs to control adverse analgesic effects, e.g. laxatives, anti emetics. Other symptoms \200 Nausea , vomiting: domperidone, cyclizine (particularly for raised intracranial pressure), methotrimeprazine, haloperidol, ondansetron, metaclopramide. Convulsions, cerebral irritati on: Spinal cord compression: bowel management. Terminal restlessness: Dyspnoea opioids, ben zodiazepines, oxygen, steroids. Excess secretions: hyoscine, glycopyrronium. diazepam, meth otrimeprazine, amitriptyline. Anxiety, depression: anticipate by prescribing laxatives when starting opioids; Constipation: select least constipating opioids (e.g. fentanyl); may nee d high enemas. Bowel obstruction: antispasmodics, stool softeners, rectal preparations to r educe impaction, octreotide to reduce secretions and vomiting. Sweating, from advanced dise ase fever or drugs: cimetidine, NSAIDs. Pruritus: cimetidine if due to disease, antihistami ne if opiate induced (anemia, hemorrhage, bruising): transfuse (blood Hematological +/ \200 \223 platelets) only for symptomatic improvement and for quality of life; topical tranexami c acid or adrenaline for troublesome mucosal bleeding. \200 diazepam, midazolam. dexamethasone, radiotherapy, bladder and \200 midazolam. : non-pharmacological measures (position, play therapy, fan), \200 \200 \200 \200 18_McClure_18.indd 691 11/14/2012 3:51:05 PM This page intentionally left blank 693 Chapter 19 Infectious diseases Introduction 694 The child with fever 696 Fever: examination and assessment 698 Fever: mana gement (green features) 700 Fever: management (red or amber features) 701 Prolonged fever o f unknown cause 702 Common infections characterized by rash 704 Exanthem 1: measles 706 Exa nthem 2: group A streptococcus 707 Exanthem 3: rubella 708 Exanthem 4: enteroviruses 708 Ex anthem 5: parvovirus 709 Exanthem 6: human herpes virus 6 709 Rash: chickenpox and zoster 7 10 Rash: infectious mononucleosis 711 Lyme disease 712 Mumps 713 Bacteraemia and shock 714 Kawasaki disease 716 Skin and soft tissues 718 Meningitis 720 Mycobacteria 722 Tropical inf ections 723 Immunode \201 ciency disorders 724 Human immunode \201 ciency virus 726 Immun izations 728 19_McClure_19.indd 693 11/14/2012 3:51:52 PM CHAPTER 19 Infectious diseases 694