Oncologic Emergencies and Cancer Pain Treatment

Oncologic Emergencies and Cancer Pain Treatment Steven Samoya, M.D. Pain Management Rotation January, 2005 Oncologic Emergencies Oncologic Emergencies in cancer patients may be related directly to the underlying cancer or may result from its treatment Classifications • Pressure or obstruction caused by spaceoccupying lesions • Metabolic or hormonal problems (paraneoplastic syndromes) • Complications of Treatment • Spontaneous • Cancer Pain Treatment Pressure/Obstruction • • • • • • • • • • • Superior Vena Cava Syndrome Pericardial Effusion/Tamponade Intestinal Obstruction Urinary Obstruction Malignant Biliary Obstruction Spinal Cord Compression Cauda Equina Syndrome Increased Intracranial Pressure Seizures Intracerebral Leukocytostasis Hemoptysis Superior Vena Cava Syndrome The clinical manifestation of obstruction of the superior vena cava, with severe reduction in venous return from the head, neck, and upper extremities. SVCS ETIOLOGY: • Lung CA makes up 70% -80% of lung CA is in Right Lung • Lymphoma and metastatic (Breast is highest) • Benign Tumors • Aortic Aneurysm • Thyroid Enlargement • Thrombosis • Fibrosing Mediastinitis (radiation/histoplasmosis) SVCS PRESENTATION/SYMPTOMS: Dyspnea (most common), neck/facial swelling, cough, hoarseness, headaches, nasal congestion, epistaxis, hemoptysis, dysphagia, pain, dizziness, syncope, lethargy. Bending down may exacerbate SVCS PRESENTATION/PHYSICAL FINDINGS: Dilated neck veins, increased collateral veins over anterior chest wall, cyanosis, edema of face, arms, chest. Severe cases include proptosis, glossal and laryngeal edema, mental obtundation. SVCS DIAGNOSIS: • Essentially Clinical • Recent onset tends to be MALIGNANCY except a SVC thrombosis • CXR: Widened superior mediastinum • CT: Most reliable view of mediastinum -diminished/absent opacificaton of central venous structures with prominent collateral venous circulation SVCS DIAGNOSIS: For those with NO history of malignancy, a detailed evaluation is necessary to rule out benign causes and to determine a specific tumor histology to direct the appropriate therapy Mediastinal irradiation before a biopsy precludes proper interpretation of specimen in half of patients SVCS TREATMENT/MANAGEMENT: • Goal is to relieve symptoms and cure the primary cause(s) • Combined therapy produces the best results with relief occurring in 7-10 days • Radiation therapy is the primary treatment due to NON small cell CA of lung and other metastatic SOLID tumors SVCS TREATMENT/MANAGEMENT: • Chemotherapy for malignancy due to SMALL cell carcinoma of lung or lymphoma • Follow chemo with radiation because these tumors tend to recur • Surgery may provide immediate relief in benign cases. • Transluminal Angioplasty may be used and anticoagulation/fibrinolytics in cases of thrombosis caused by central line catheters SVCS • The absolute emergency that occurs is TRACHEAL OBSTRUCTION. • Diuretics with a low salt diet, head elevation, and oxygen may produce temporary symptom relief Pericardial Effusion/Tamponade FACTS: • Found in 5-10% of patients with CA • Most frequent in lung, breast, leukemia/lymphoma • Often due to irradiation. TWO TYPES: 1. Acute inflammatory-effusive 2. Chronic effusive PERICARDIAL EFFUSION/TAMPONADE DIAGNOSTIC FINDINGS: • SXS: dyspnea, cough, chest pain, orthopnea and weakness • Physical Findings: Pleural Effusion, sinus tachycardia, jugular venous distension, hepatomegaly, peripheral edema, and cyanosis PLEURAL EFFUSION/TAMPONADE DIAGNOSTIC: • paradoxical pulse, diminished heart sounds, pulsus alternans and friction rub are LESS common in malignant disease than in nonmalignant • CXR and ECG: ABNORMAL in 90%, but half of these are NONspecific • Echo: The most helpful diagnostic test • Cytologic exam of pericardial fluid is diagnostic in most patients PERICARDIAL EFFUSION/TAMPONADE TREATMENT: • Malignant pericardial effusions call for pericardiocentesis with or without the introduction of sclerosing agents, the creation of pericardial window, complete pericardial stripping, cardiac irradiation, or systemic chemo • Acute pericardial tamponade with life-threatening hemodynamic instability requires immediate drainage of fluid via pericardiocentesis or subxyphoid pericardiotomy SVC Syndrome vs. Tamponade TAMPONADE: • Pericardial fluid pressure is elevated/jugular vein distended initially but returns to normal as the fluid is withdrawn SVC SYNDROME: • Pericardial fluid pressure is normal and jugular venous pressure (which is high) is unaffected by the pericardiocentesis. Intestinal Obstruction ETIOLOGY: • Common problem in advanced cancer (colorectal and ovarian most common). • Ileus can be caused by vincristine and is usually reversible PRESENTATION/DX: • Pain is most common symptom (colicky) • Vomiting can be intermittent or continuous • Abdominal distension with tympany, ascites, visible peristalsis, high-pitched bowel sounds, tumor masses • KUB (erect): may reveal multiple air-fluid levels and dilatation TREATMENT: • Cecal dilation of more than 12 to 14 cm is considered a surgical emergency because of high likelihood of rupture • Overall prognosis of CA patient with obstruction is POOR/median survival 3-4 months Urinary Obstruction ETIOLOGY: • Prostatic or Gynecologic malignancies (cervical carcinoma) • Radiation therapy to pelvic tumors may cause fibrosis and subsequent ureteral obstruction. • Bladder outlet obstruction usually due to prostate and cervical CA SIGNS/SXS: • Flank pain (most common), persistent UTI, persistent proteinuria, hematuria in patients with CA should ALERT PHYSICIAN • Total Anuria or anuria alternating with polyuria may occur • SLOW, CONTINUOUS rise in serum creatinine value necessitates IMMEDIATE evaluation in patients with CA. Renal U/S is best way to ID hydronephrosis Urinary Obstruction TREATMENT: • Bilateral obstruction of ureters or bladder outlet obstruction requires immediate attention • Internal ureteral stent placement under local • Percutaneous nephrostomy for drainage • Suprapubic cystostomy for drainage in the case of bladder outlet obstruction due to malignancy Malignant Biliary Obstruction ETIOLOGY: • Caused by a primary carcinoma arising in the pancreas, ampulla of Vater, bile duct, or liver or by METS disease to the periductal lymph nodes or liver parenchyma. Most common are GASTRIC, COLON, BREAST, LUNG Jaundice, light-colored stools, dark urine, pruritis, weight loss due to malabsorption. Pain and secondary infection are uncommon in malignant biliary obstruction. U/S, CT, Percutaneous transhepatic or endoscopic retrograde cholangiography (ERCP) ID the site and nature of the biliary obstruction PRESENTATION/SXS: • DIAGNOSIS: • TREATMENT: • • Palliative Intervention indicated ONLY in patients with disabling pruritus resistant to medical treatment, severe malabsorption, or infection. Stenting under radiographic control, surgical bypass, or xrt treatment based on site of obstruction (proximal vs distal), type of tumor, and general condition of the patient. Spinal Cord Compression FACTS: • Occurs in 5-10% of patients with CA • Epidural tumor is the first manifestation of malignancy in about 10% of patients • Lung CA is the most common primary (breast and prostate follow) • Metastatic tumor involves the vertebral column more often than any other part of the bony skeleton Spinal Cord Compression • • • • Thoracic spine, lumbosacral, then cervical (70-20-10) Breast/Prostate produce MULTIPLE lesions Lung Carcinoma produce SINGLE lesion Cord injury occurs when mets to vertebral body or pedicle enlarge and compress the underlying dura, or by direct extension of a paravertebral lesion through the intervertebral foramen (lymphoma, myeloma or pediatric neoplasm) • Rarely, hematogenous spread to parenchyma of cord occurs Spinal Cord Compression SIGNS/SXS: • Localized back pain is most common initially, and tenderness due to involvement of vertebrae by tumor • Pain usually present for days/months before neuro findings appear. Exacerbated by cough/sneeze • DIFFERENTIATED from disc disease by the fact that this pain is WORSE WHEN SUPINE (disc is worse when sitting) Spinal Cord Compression PHYSICAL EXAM FINDINGS: • Pain on straight leg raising, neck flexion, vertebral percussion may help to locate level of lesion • Numbness/paresthesias in extremities or trunk • Loss of sensation to pinprick, vibration and proprioception can occur • Weakness, spasticity, abnormal muscle stretching • Loss of sphincter tone occurs later/distended bladder Management of CA patient with Back Pain BACK PAIN NORMAL Neuro Exam Suspcious for Myelopathy MRI Plain Spine Radiographs High-Dose Dexamethasone Epidural Metastases Normal NO metastases Abnormal Radiation Therapy and Dexamethasone Symptomatic Therapy Bone Mets NO epidural Mets Radiation Therapy Spinal Cord Compression DIAGNOSTIC: • “Winking Owl” sign (Erosion of Pedicles) is earliest radiologic finding of vertebral column tumor • Other Radiographic: Increased intrapedicular distance, vertebral destruction, lytic or sclerotic lesions, scalloped vertebral bodies, and vertebral body collapse • MRI: Full-length image of cord -T1 weighted images demonstrate good contrast between the cord, CSF, and extradural lesions -T2 weighted images demonstrate intramedullary bone pathology Spinal Cord Compression TREATMENT: • Directed toward pain relief/restore neuro function • Radiation plus glucocorticoids is generally initial TX of choice for compression • Approx. 75% remain ambulatory when initial TX takes place when ambulatory. Only 10% of others regain ability to ambulate • Laminectomy ONLY used for tissue diagnosis and for removal of posteriorly localized epidural deposits in ABSENCE of vertebral disease • Most cases are Anterior/Anterolateral -Resection of anterior vertebral body along with tumor, then stabilize spine -Good results with low mortality • Rapid onset and quick progression are POOR prognostic features Cauda Equina Syndrome Signs/Symptoms: • • • • Severe back pain with radiculopathy Saddle distro sensory loss Diminished anal sphincter tone Urinary retention or incontinence SURGICAL EMERGENCY!!!! Increased Intracranial Pressure FACTS: • 25% cancer patients die with intracranial mets • Brain, Lung, Breast and Melanoma • Onset can be abrupt, resembling stroke Increased Intracranial Pressure Signs/Sxs: • Headache, nausea, vomiting, behavioral changes, seizures, and focal progressive neurologic changes • Abrupt onset usually due to hemorrhage into metastasis (melanoma, germ cell, and renal cell) -Tumor mass and surrounding edema cause obstruction of circulation of CSF, resulting in hydrocephalus -Results in papilledema with visual disturbances/neck stiffness -Herniation Increased Intracranial Pressure DIAGNOSIS: • CT and MRI: equally effective in DX of mets • CT with contrast: used as Screening. Shows brain mets as multiple enhancing lesions of various size with surrounding areas of low-density edema • MRI: performed if there is a single lesion or if NO mets visualized by contrast enhanced CT • GADOLINIUM MRI: more sensitive than CT for small lesions, particularly in brainstem or cerebellum Increased Intracranial Pressure TREATMENT: • If signs/symptoms of Brain Herniation (headache, drowsiness, papilledema) present, patient should be intubated and hyperventilated to maintain PCO2 between 25-30 mmHg and should receive infusions of mannitol (1-1.5 g/kg) every 6 hours. • Dexamethasone is best initial treatment for all symptomatic patients with brain mets • Multiple lesions should receive whole-brain radiotherapy • Single lesions may be treated with surgical excision followed by whole-brain radiotherapy (particularly if younger than 60 y.o.) Other • Seizures -Metastatic disease to CNS is the most common cause of seizures in cancer patients. Published reports range from frequency of 6-29% in which seizures are a presenting symptom of intracranial mets. -Frontal lesions correlate with early seizure -Posterior fossa lesions rarely cause seizure • Intracerebral Leukocytostasis -”Ball’s Disease”. Potentially fatal complication of Acute Leukemia (myelogenous) that occurs when the peripheral blast cell count is greater than 100K/uL. -Such high blast count INCREASES blood viscosity and slows flow Other • Hemoptysis -Usually caused by nonmalignant conditions -Older patients with lung CA or lung mets, who have coagulation defects or thrombocytopenia are susceptible -Volume of bleeding difficult to assess accurately -Treat EMERGENTLY WITH BRONCHOSCOPY • Airway Obstruction -Obstruction proximal to larynx? Tracheostomy is life-saving -Distal obstruction? Use either external-beam irradiation or brachytherapy, along with glucocorticoids to open airway Metabolic Emergencies • Hypercalcemia • Syndrome of Inappropriate Secretion of Antidiuretic Hormone (SIADH) • Lactic Acidosis • Hypoglycemia • Adrenal Insufficiency Hypercalcemia • The most common paraneoplastic syndrome, occuring in 10% of patients with advanced cancer • Most often Lung, Breast, Head and Neck, Kidney, and Multiple myeloma • Increased release of calcium from bone is the main factor Hypercalcemia Pathophysiology: • Bone resorption is increased dramatically via stimulation of proliferation and activity of osteoclasts and bone formation is not stimulated in parallel • Kidney may resorb more calcium in the distal tubule • Parathormone-related protein produced by tumors is central mediator of increased calcium in cancer Hypercalcemia Clinical Features: • Fatigue, anorexia, constipation, polydipsia, muscle weakness, nausea, and vomiting • Easily attributed to the cancer itself or its treatment so it can be missed Laboratory: • Order electrolytes, calcium, phosphate, albumin • Use corrected for protien formula to find calcium concentration when ionized calcium is unobtainable Hypercalcemia TREATMENT: • moderate to severe >12 mg/dL • Treatment directed at hypercalcemia only extends life in patients for whom effective cancer treatment is available. Corrective therapy may be indicated on a palliative basis to improve symptoms and quality of life • IV saline to resore intravascular volume • Antiresorptive agents are ESSENTIAL to decrease osteoclast activity • BISPHOSPHONATES are potent inhibitors of bone resorption, virtually free of side effects (Pamidronate is most effective) • Gallium Nitrate inhibits osteoclast function. Risk of nephotoxicity Syndrome of Inappropriate Secretions of Antidiuretic Hormone (SIADH) • Caused by production of arginine vasopressin by tumor cells -HYPOnatremia -increase urine osmolarity above plasma -increased sodium excretion in urine without volume depletion -often co-secretion of adrenocorticotropic hormone (ACTH) • Small cell carcinoma of lung • Cytotoxic drugs vincristine, ifosfamide, cyclophosphamide, cisplatin SIADH • Most patients are asymptomatic • Degree of symptoms and severity are due to: -degree of hyponatremia -rapidity hyponatremia develops SYMPTOMS: • Early anorexia, depression, lethargy, irritability, confusion, muscle weakness, marked personality changes • Plasma sodium falls below 110 mEq/L, extensor plantar responses, areflexia, and pseudobulbar palsy may be noted • Can lead to coma, convulsions, death SIADH TREATMENT: • Treat underlying Malignancy • Restrict water • Democlocycline used first. Inhibits effects of vasopressin on distal renal tubule Other Metabolic • Lactic Acidosis -Rare and potentially fatal metabolic complication of cancer. -Lactic acidosis, associated with sepsis and circulatory failure is a common preterminal event in many malignancies -Alteration in Liver function is present in most cases -Tachypnea, tachycardia, change of mental status, hepatomegaly TREATMENT: -Aimed at underlying disease -Acidosis is the killer. Add sodium bicarb if acidosis is very severe or if hydrogen ion production is very rapid and uncontrolled. Other Metabolic • Hypoglycemia -Occasionally associated with tumors OTHER than pancreatic islet cell tumors. Often mesenchymal origin (retroperitoneum or thorax usually) -Obtundation, behavioral changes, confusion all occur in postabsorptive period and may precede the diagnosis of tumor • Adrenal Insufficiency -May go unrecognized in cancer patients because the symptoms (nausea, vomiting, anorexia, and orthostatic hypotension) are nonspecific and may be attributed to progressive cancer or therapy -Lung, Breast, Colon, Kidney all like to go to adrenal glands Treatment-Related Emergencies • • • • • • • Tumor Lysis Syndrome Hemolytic-Uremic Syndrome Neutropenia and Infection Pulmonary infiltrates Typhlitis Hemorrhagic Cystitis Treatment of Acute Promyelocytic Leukemia Tumor Lysis Syndrome • Most frequently associated with treatment of Burkitt’s lymphoma, acute lymphoblastic leukemia, and high grade lymphomas • May be seen with chronic leukemias • Rare in Solid tumors Tumor Lysis Syndrome Etiology: • Destruction of malignant cells leads to increased uric acid levels from the turnover of nucleic acids • Tumor cell lysis causes release of intracellular phosphate pools. Leads to depression of serum calcium • Massive destruction of malignant cells releases potassium, the principal intracellular cation • Usually occurs 1-5 days post chemo Tumor Lysis Syndrome Presentation: • Various combinations of -Hyperuricemia -Hyperkalemia -Hyperphosphatemia -Lactic Acidosis -Hypocalcemia Tumor Lysis Syndrome PREVENTION/MANAGEMENT: • Patients at risk: -Burkitt’s lymphoma -likelihood of the syndrome in Burkitt’s is related to tumor burden and renal function. Hyperuricemia and high serum levels of Lactate Dehydrogenase (LDH) (>1500 units/L), both of which correlate with total tumor burden, and correlate with the risk of posttreatment tumor lysis syndrome -Recognition of risk and prevention are the most important steps in the management of this syndrome Tumor Lysis Syndrome Presentation/Diagnosis: • Uric acid can precipitate in tubules, medulla, and collecting ducts of kidney leading to RENAL FAILURE. Uric acid crystals in Urine • Lactic Acidosis and dehydration may contribute to precipitation of uric acid in the renal tubules • Deposition of calcium phosphate in kidney and hyperphosphatemia may cause renal failure and a decrease in serum calcium leading to severe neuromuscular irritability and tetany • Ventricular arrhythmia’s and sudden death can be caused by hyperkalemia, particularly when renal failure is present Tumor Lysis Syndrome Treatment: • • • • dialysis often necessary should be considered early in course Hemodialysis is preferred Prognosis is excellent and renal function recovers after the uric acid level is lowered to less than 1020 mg/dL Hemolytic-Uremic Syndrome • Caused by antineoplastic drugs Mitomycin, Cisplatin, Bleomycin • Occurs most often in patients with Gastric, Colorectal, Breast Carcinoma • Onset is 4-8 weeks after last dose of chemo CHARACTERISTICS: • • • Microangiopathic hemolytic anemia Thrombcytopenia Renal Failure PRESENTATION: • • • INITIALLY; Dyspnea, weakness, fatigue, oliguria, purpura LATER; Systemic HTN, pulmonary edema are common Atrial arrhythmias, pericardial friction rub, pericardial effusion Hemolytic Uremic Syndrome Laboratory: • Severe/moderate anemia assoc’d with RBC fragmentation and schistocytes on peripheral smear • Reticulocytosis, decreased plasma haptoglobin, elevated LDH all point to hemolysis taking place • WBC count usually normal • Most patients have normal coagulation profile with possible elevation in thrombin time and in level of fibrin degradation products • Serum creatinine level is ELEVATED and shows pattern of subacute worsening within weeks of initial azotemia • UA reveals hematuria, proteinuria, granular or hyaline casts, immune complexes may be present Hemolytic Uremic Syndrome FACTS: • Basic pathologic lesion is deposit of fibrin in walls of capillaries and arterioles • This involves the kidneys mainly • Pathogenesis is unknown….thought to be immune complexes • Fatality rate is high with most patients dying within a few months • Renal failure is NOT reversed in most patients • Immunoperfusion of a staphylococcal protein A column is the MOST EFFECTIVE TREATMENT (half of the patients treated this way respond with resolution of thrombocytopenia, improvement in anemia, and stabilization of renal failure (not reversal) Neutropenia and Infection These remain the most common serious complications of cancer therapy Pulmonary Infiltrates ETIOLOGY: • • • • • Progression of underlying malignancy Treatment-related toxicities Infection Multifactorial Accumulation of leukemic blasts in the pulmonary capillary system Pulmonary Infiltrates PRESENTATION/DIAGNOSIS: • • • • Dyspnea Diffuse interstitial infiltrates on CXR Non productive cough, tachycardia Dizziness, confusion, tinnitus, ataxia, visual blurring, retinal abnormalities due to leukostasis in cerebral vessels • Bacterial pneumonia (Pneumocystis carinii, CMV, mycoplasma, legionella) Pulmonary Infiltrates Cytotoxic agents causing pulmonary damage: • • • • • • Bleomycin Methotrexate Busulfan Nitrosureas Procarbazine Mitomycin C Pulmonary Infiltrates • TREATMENT: • Glucocorticoids can provide symptomatic relief • Supplemental Oxygen at lowest FIO2 able to maintain hemoglobin saturation • Prednisone should be administered if you find fever post radiation Other Treatment Induced • Typhlitis - necrosis of cecum and adjacent colon that may complicate the treatment of acute leukemia. Right lower Quadrant pain, distended abdomen, fever and neutropenia. Watery diarrhea and bacteremia are common - Treat with broad-spectrum antibiotic and nasogastric suction -consider surgical intervention if no improvement by 24 hrs after start of antibiotic treatment. • Hemorrhagic Cystitis -Cyclophosphamide or ifosfamide both metabolized to ACROLEIN, a strong irritant Types of Pain in Cancer • Somatic Nociceptive • Visceral • Neuropathic Somatic Pain • Typical pain we all experience: • Cutaneous burn • Arthritic joint • • • • Painful site is tender and corresponds to the site of tissue damage Described as constant, sometimes throbbing or aching Bone mets are the most common malignant cause Bone mets are the most common source of pain in cancer Visceral Pain • Originates from viscera • Abdominal cramps • Renal stone pain • Less common than somatic, is dull, and colicky • Poorly localized, often referred to cutaneous site • Often with accompanying nausea and diaphoresis Neuropathic Pain • • • • Nerve root compression from herniated disc Prolonged, severe, burning, lancinating, squeezing Often accompanied by neuro deficits Allodynia-exquisite sensitivity to normally innocuous stimuli • Resistant to opioids • Direct infiltration of neural structures is the most common cause of this pain in cancer patients • XRT and surgical injury are other causes Bone Pain • Tumor involvement of bone most common • Purely somatic unless pathologic fracture or tumor extension involves nerve • Described as focal and constant, but may be referred • Vertebral column, skull, humerus, ribs, pelvis and femur • Note that a bone scan is often normal in lytic lesions of multiple myeloma and previously irradiated bone Treatment Somatic/Bone: • NSAIDS, Steroids, Opioids, Bisphosphonates, Calcitonin Visceral: • Opioids Neuropathic: • Neurontin, Amitriptyline, corticosteroids, neuroleptics for refractory pain, oral and local anesthetics Direction of Treatment • Use the WHO ladder in guiding your prescribing of medications • Consider drug selection, route selection, dosing and titration, trials of alternative opioids, side effects, and monitoring • Adjust REFERENCES • Principles and Practice of Pain Medicine, Warfield and Bajwa, McGraw Hill, 2004. • Harrison’s, Mosby, Chapter 104, McGraw Hill, 1999. • Cancer: Principles and Practice of Oncology, 4th Ed., Vincent DeVita, etal,, Lippincott, Chapter 60, 1993. • Johns Hopkins: Hariett Lane Handbook, 15th Ed., Mosby, 2000. • Oncologic Emergencies. Neilan BA. Treating acute problems resulting from cancer and chemotherapy. Postgrad Med, 1994:95:131 • Skeletal Complications of Malignancy. Cancer 1997:80:1588. (A review of a variety of complications involving skeleton, including spinal cord compression)