Oncological emergencies

Oncology

1. ONCOLOGICAL EMERGENCIES Dr.N.Vasu Babu

2. INTRODUCTION CARDIOVASCULAR- 1)SUPERIOR VENACAVA SYNDROME 2)PERICARDIAL EFFUSION CENTRAL NERVOUS-1)SPINAL CORD COMPRESSION 2) CARCINOMATOUS MENINGITIS METABOLIC- 1)HYPERCALCEMIA 2)TUMOR LYSIS SYNDROME 3)SIADH 4)HYPOGLYCEMIA 5)HYPERURECEMIA 6)ADRENAL FAILURE HEAMATOLOGICAL- 1) LEUCOSTASIS 2) HYPERVISCOSITY SYNDROME 3) POLYCYTHEMIA AND LEUKOCYTOSIS OTHERS- 1)NEUTROPENIC FEVER

3. 1.SUPERIOR VENACAVA SYNDROME Superior vena cava syndrome (SVCS) is the clinical expression of obstruction of blood flow through the SVC. Characteristic symptoms and signs may develop quickly or gradually when this thin-walled vessel is compressed, invaded, or thrombosed by processes in the superior mediastinum . The first pathologic description of SVC obstruction, in a patient with syphilitic aortic aneurysm, appeared in 1757. cancer of the lung -approximately 70% of patients with SVCS.

4. SUPERIOR VENACAVA SYNDROME Before antibiotics the most common causes were from complications of untreated infection Syphilitic thoracic aneurysms fibrosing mediastinitis Malignancy is presently the most common cause Malignant disease can arise in weeks to months Not enough time to develop collaterals Fibrosing mediastinitis can take years to have symptoms

5. SUPERIOR VENACAVA SYNDROME Lung cancer is the most common Lymphoma is second most common together represent 94% of cases 2-4% of bronchogenic cancer patients develop SVC syndrome by extrinsic compression or direct invasion. Thymoma primary mediastinal germ cell neoplasm solid tumors with mediastinal nodal metastases breast cancer most common type Post radiation local vascular fibrosis can also be considered in oncology patients Thrombosis Indwelling central venous catheters

6. SUPERIOR VENACAVA SYNDROME Small cell-38% Squamous cell-26% Adenocarcinoma-14% Large cell-12% Unclassified-9%

7. SUPERIOR VENACAVA SYNDROME SIGNS AND SYMPTOMS Central venous pressures remain high even in collaterals High pressures cause the characteristic clinical picture Shortness of breath is the most common symptom Facial swelling or head fullness exacerbated by bending forward or lying down Cough Arm edema Cyanosis Venous distension neck chest wall

8. SUPERIOR VENACAVA SYNDROME SYMPTOMS- DYSPNEA-63% FACIAL SWELLING AND HEAD FULLNESS-50% COUGH-24% ARM SWELLING-18% CHESTPAIN-15% DYSPHAGIA-9% PHYSICAL FINDINGS- VENOUS DISTENSION OF NECK-66% VENOUS DISTENSION OF CHEST WALL-54% FACIAL EDEMA-46% CYANOSIS-23% PLETHORA OF LUNG-19%

9. SUPERIOR VENACAVA SYNDROME

10. SUPERIOR VENA CAVA SYNDROME Patient who presented with progressively enlarging veins over the anterior chest wall. A diagnosis of a right-sided superior sulcus ( Pancoast ) tumor compressing the SVC was made.

11. SUPERIOR VENACAVA SYNDROME DIAGNOSIS- Diagnostic procedures, such as bronchoscopy,mediastinoscopy , thoracotomy , or supraclavicular lymph node biopsy, were often avoided because they were considered to be hazardous in the presence of SVCS. The clinical identification of SVCS is simple because the symptoms and signs are typical and unmistakable. The chest film shows a mass in most patients. Only 16% of the patients studied by Parish had normal chest films. The most common radiographic abnormalities are superior mediastinal widening and pleural effusion.

12. SUPERIOR VENACAVA SYNDROME CT phlebography provides excellent imaging information on the site and extent of obstruction and the status of collaterals. Helical CT phlebography replaced the combination of CT and digitalphlebography that was advocated in the past. Contrast venography provides important information for determining if the vena cava is completely obstructed or remains patent and extrinsically compressed

13. SUPERIOR VENACAVA SYNDROME Radionuclide technetium ( Tc ) 99m venography is an alternative, minimally invasive method of imaging the venous system Gallium single photon emission CT may be of value in selected cases. In 58% of 107 patients reported by Schraufnagel et al. the SVCS developed before the primary diagnosis was established.

14. SUPERIOR VENA CAVA SYNDROME TREATMENT- RADIATION THERAPY- Radiotherapy is an optional treatment for most patients with SVCS. It is also used as an effective initial treatment if a histologic diagnosis cannot be established and the clinical status of the patient is deteriorating. Some reviews suggest that SVC obstruction alone rarely represents an absolute emergency that requires radiotherapy without a specific diagnosis, and endovascular stenting may be used as an alternative to radiotherapy for obtaining immediate relief of the obstruction

15. SUPERIOR VENACAVA SYNDROME The fractionation schedule of radiation that has been recommended includes two to four large initial fractions of 3 to 4 cGy , followed by conventional fractionation to a total dose of 30 to 50 cGy . No data clearly support a particular fractionation scheme. In one study, patients treated with initial high-dose fractions showed a slightly faster symptomatic improvement than patients receiving conventional-dose radiation. Improvement within 2 weeks or less was observed in 70% of those treated with initial high-dose fractions and in 56% of patients receiving conventional-dose therapy. This difference was not statistically significant

16. SUPERIOR VENACAVA SYNDROME ENDOVASCULAR STENTING AND ANGIOPLASTY- endovascular therapy— thrombolysis , angioplasty, and stent therapy. SURGERY- It was recommended that autologous grafts of almost the same size as the SVC should be used. Doty et al. used a composite spiral graft, which was constructed from the patient's saphenous vein. Dacron protheses polytetrafluoroethylene prosthesis The preferred bypass route is between an innominate or jugular vein on the left side and the right atrial appendage, using an end-to-end anastomosis .

17. SUPERIOR VENACAVA SYNDROME THROMBOLYTIC THERAPY- Successful experience with thrombolytic agents was also obtained in the treatment of catheter-induced SVCS. Urokinase was more effective than streptokinase, and a delay administering therapy beyond 5 days of symptom onset was associated with a treatment failure.

18. SUPERIOR VENACAVA SYNDROME General measures- Bed rest with the head elevated and oxygen administration can reduce the cardiac output and venous pressure. Diuretic therapy and a reduced-salt diet to reduce edema may have an immediate palliative effect, but the risk of thrombosis enhanced by dehydration should not be ignored.

19. SPINAL CORD COMPRESSION Malignant spinal cord compression is defined as the compressive indentation, displacement, or encasement of the spinal cord's thecal sac by metastatic or locally advanced cancer. Compression can occur via posterior extension of a vertebral body mass, resulting in compression of the anterior aspect of the spinal cord, or through anterior or anterolateral extension of a mass arising from the dorsal elements or invading the vertebral foramen, respectively. Intramedullary spinal cord metastases produce edema , distortion, and compression of the spinal cord parenchyma, resulting in symptoms and signs that are similar to epidural spinal cord compression

20. SPINAL CORD COMPRESSION In adults, metastatic spinal cord compression occurs in roughly 3.0% to 7.4% of patients with lung, prostate, and breast cancer and the overall frequency of malignant spinal cord compression has been reported to be approximately 5%.

21. SPINAL CORD COMPRESSION Spinal cord damage and loss of neurologic function result from venous stasis, spinal cord edema , reduced capillary blood flow, ischemia, and mechanical compression culminating in infarction. Prostaglandins, cytokines, excitatory neurotransmitters, and inflammatory mediators regulate the sweeping pathophysiologic changes associated with hypoxia, edema , ischemia, and injury resulting from malignant compression

22. SPINAL CORD COMPRESSION CLINAICAL PRESENTATION The most frequently involved site is the Thoracic spine (59% to 78%) Lumbar spine (16% to 33%) Cervical spine (4% to 15%). Multiple epidural sites of compression can occur in 26% to 49%. Intramedullary cord compression, accounting for only 1% to 4% of cases, is usually solitary and is often associated with parenchymal brain metastases

23. SPINAL CORD COMPRESSION PAIN-96% WEAKNESS-86% SENSORY DYSFUNCTION-80% AUTONOMIC DYSFUNCTION-64%

24. SPINAL CORD COMPRESSION The pain may be local, radicular , or both. Local pain is present in the vast majority of cases and is caused by expansion, destruction, or fracture of the involved vertebral elements. The site of compression can usually be localized to the site of back or neck pain. Local back or neck pain is usually dull, aching, constant, and progressive. Back pain from vertebral destruction resulting in retropulsion of bone fragment is often worse in the supine position, a feature distinguishing cord compression from a herniated disc Local back or neck pain can be exacerbated by movement, sneezing, straining, or neck flexion.

25. SPINAL CORD COMPRESSION Bilateral band-like girdle pain is characteristic of thoracic cord lesions, and unilateral radicular pain is more characteristic of lumbar or cervical lesions. Radicular pain from a cervical or lumbar lesion may involve the shoulder, hip, groin, perineum, or extremity. Complete loss of motor and sensory function below the affected level (cord shock) can occur abruptly as vascular insufficiency progresses to frank ischemia.

26. SPINAL CORD COMPRESSION Neurologic examination of the patient with cord shock reveals absent motor, sensory, reflex, and autonomic function below the level of the lesion, and the affected extremities demonstrate flaccidity and absence of tone. Absence of perineal and anal reflexes and painless overflow incontinence complete the neurologic presentation. Flaccidity and areflexia are gradually replaced by paraplegia in flexion. Compression of the upper cervical spinal cord can produce paralysis of the upper extremities and respiratory failure, if acute. Lesions involving the conus medullaris or cauda equina produce flaccid paralysis of the lower extremities, absent or flexor plantar responses, saddle anesthesia , urinary retention leading to incontinence, and male impotence

27. SPINAL CORD COMPRESSION DIAGNOSTIC EVALUATION- Plain film radiographs detect the presence and location of epidural metastases in 83% of patients complaining of back pain. Vertebral body collapse, destruction of the pedicle, and blastic or sclerotic changes are characteristic findings observable with plain film radiography. Myelography has the advantage over plain films of visualizing the level of the compression as indicated by a blockage of myelographic contrast. Multiple sites of compression, which may be present in greater than 30% of cases, may require more than one subarachnoid puncture

28. SPINAL CORD COMPRESSION Bone scintigraphy is more sensitive than plain films in detecting metastatic involvement and provides information about the entire skeleton in a single examination. Bone scintigraphy is not as sensitive and specific in detecting spinal metastases as MRI and is incapable of describing the soft tissue and spinal cord anatomy required for the proper diagnosis and treatment of cord compression. Furthermore, primarily osteolytic metastases produced by multiple myeloma, lymphoma, and other malignancies may not be detected by bone scan.

29. SPINAL CORD COMPRESSION CT SCAN MRI SCAN- MRI has a sensitivity of 93%, a specificity of 97%, and an overall diagnostic accuracy of 95% in detecting cord compression. Paraspinous and neuroforaminal tumors are not as easily identified with myelography as with MRI. In addition, MRI allows avoidance of neurologic deterioration following lumbar puncture for myelography . MRI excels in demonstrating intramedullary metastases that can be missed completely by myelography . The advantages of MRI over CT include its ability to distinguish the spinal cord proper from other soft tissue masses in the spinal canal.

30. SPINAL CORD COMPRESSION A sagittal T1 nonenhanced survey of the entire spine quickly and easily identifies multiple sites of compression and should guide the acquisition of axial views through areas of involvement. Bone metastases appear as dark botches relative to normal bone marrow in unenhanced T1 images. CSF and edematous tumor appear bright on T2 sequences. T2 sequences display CSF brightly, producing images that are similar to a myelogram . Axial T2 sequences can be useful in identifying small tumor nodules on nerve roots. Focal blastic lesions may produce decreased intensity on T2 images.

31. MRI with contrast is the imaging study of choice to diagnose spinal cord compression **CT scans maybe used if MRI contraindicated

32. SPINAL CORD COMPRESSION TREATMENT- The results of treatment of cord compression have improved in recent years as a result of earlier diagnosis with the greater availability of MRI and due to a heightened awareness of cord compression as a potential oncologic emergency. The pretreatment degree of neurologic dysfunction is the strongest predicator of therapeutic outcome. Eighty percent to 100% of patients with minimal or no ambulatory dysfunction retain ambulation post treatment. Paraparesis improves with treatment in 34% to 63% of cases, whereas paraplegia improves in up to 10% to 55% of cases

33. SPINAL CORD COMPRESSION CORTICOSTEROIDS- Corticosteroids ( dexamethasone , methylprednisolone ) Dexamethasone reduces edema , inhibits PGE2 synthesis, and decreases the specific gravity of the compressed spinal cord. It also was shown to delay the onset of paraplegia in experimental cord compression. A prospective randomized study comparing a single high dose of intravenous dexamethasone (100 mg) with conventional dose intravenous dexamethasone (10 mg), both followed by 4 mg orally every 6 hours, demonstrated no significant benefit for the initial high-dose bolus

34. SPINAL CORD COMPRESSION SURGERY- Although radiation therapy is currently the treatment of choice for most spinal metastases, radioresistant and recurrent neoplasms remain therapeutic dilemmas. Accepted indications for surgery are (1) unknown diagnosis, (2) spinal instability or compression by bone, (3) failure to respond to radiotherapy, and (4) maximalallowable radiation dose already administered to the spinal cord. LAMINECTOMY Anterior decompression

35. SPINAL CORD COMPRESSION Anterior decompression with mechanical stabilization has supplanted laminectomy as the principal surgical treatment for epidural metastases arising from the vertebral body. This approach allows total removal of the pathologic vertebral body via thoracotomy or a retroperitoneal approach. The vertebral body is replaced with methylmethacrylate , which is supplemented with a metal prosthesis that attaches to the adjacent vertebral bodies

36. SPINAL CORD COMPRESSION RADIATION THERAPY- Radiation plays a central role in the treatment of newly diagnosed epidural cord compression. Greenberg et al., treated patients with hypofractionated radiotherapy and initial high-dose dexamethasone . Patients received 100 mg of intravenous dexamethasone and 500 cGy per fraction daily for the first 3 days of treatment. Following a 4-day rest, radiation was continued in 300-cGy fractions to a total dose of 3000 cGy . Fifty-seven percent of patients were ambulatory after treatment.

37. SPINAL CORD COMPRESSION Radioresponsive tumors , such as neuroblastoma , can be treated with 2000 to 3000 cGy . Epidural cord compression caused by lymphoma more often responds completely when total doses greater than 2500 cGy are employed. Patients with cord compression by malignant melanoma are more likely to respond to total doses greater than 3000 cGy .

38. SPINAL CORD COMPRESSION Complete recovery is more often associated with higher total doses, rather than with the use of large doses per fraction. some radiotherapists continue to recommend delivery of large doses per fraction (400 to 500 cGy ) on the first 3 days of treatment to achieve rapid lysis of tumor , followed by smaller doses (200 to 300 cGy ) for the remainder of the treatment. By convention, patients usually receive 200 to 300 cGy per fraction to a total dose not exceeding 3000 to 4000 cGy to the spinal cord in 2 to 4 weeks.

39. SPINAL CORD COMPRESSION CHEMOTHERAPY- In adults, cytotoxic chemotherapy and hormonal therapy have been used to successfully alleviate spinal cord compression from prostate cancer, Hodgkin's disease, myeloma, germ cell tumors , lymphoma, and breast cancer. The use of chemotherapy combined with radiation was associated with a prolonged survival in patients presenting with epidural cord compression from non-Hodgkin's lymphoma.

40. NEUTROPENIC FEVER Extremely common emergency in oncology Up to 70% mortality rate at 48 hours Neutropenic : ANC ( polys and bands) < 500 Fever: One reading of 101.3 (38.3) 100.4 (38) for more than one hour steroids, sick, hypotension even in the absence of fever

41. NEUTROPENIC FEVER Sources Enteric Bacteria Skin Flora Community Acquired Agents Iatrogenic/Instrumentation Agents Gram Negative Rods Gram Positive Cocci Fungi Other

42. NEUTROPENIC FEVER Treatment Begin therapy within 4 hours of fever spike Monotherapy cheaper, safer equaly effective as dual therapy in uncomplicated neutropenic fever( Cefepime , Imipenem , Meropenem ) Dual therapy offers synergy against GNR and may be preferred in sicker patients or those with focal infections requiring broader coverage (pneumonia). Regimen must always include anti- pseudomonal coverage

43. NEUTROPENIC FEVER Risk stratification Need for vancomycin – Cellulitis , severe mucositis – Infected catheter – Hypotension, signs of sepsis – Known MRSA colonization – Prior quinolone prophylaxis Need for anaerobic coverage – Gingivitis – Bowel involvement/rectal abscess

44. NEUTROPENIC FEVER

45. NEUTROPENIC FEVER Addition of antifungal Incidence rises after 7 days of antibiotics with persistent fever and neutropenia Antifungal added at 5-7 days of persistent F+N – Liposomal ampho as effective as ampho , less toxic, fewer breakthrough fungal infections – Voriconazole vs ampho : same mortality, – Caspofungin vs ampho : better mortality and fewer SE – Intraconazole (avoid in renal insufficiency and for longer than 14 days) When patient’s ANC resolves and afebrile , one can discontinue meds one by one Amphotericin → vancomycin → cefepime

46. NEUTROPENIC FEVER Duration of therapy • If pathogen identified: treat as indicated • If ANC rises and F stops: can stop A • If F resolves but N persists: – Consider stopping with early signs of hematologic recovery, but watch closely.

47. NEUTROPENIC FEVER Growth factors (CSFs) for febrile neutropenia - Minor clinical benefit documented – Shorter duration of neutropenia – Quicker resolution of fever – Shorter hospital stay – No difference in mortality May be more effective in high risk

48. HYPERCALCEMIA Hypercalcemia is the most common life-threatening metabolic disorder in patients with cancer. The prevalence of this disorder approximates 15 to 20 cases per 100,000 persons. The incidence varies depending on the underlying cancer diagnosis, being highest in myeloma and breast cancer (approximately 40%),intermediate in non–small cell lung cancer, and uncommon in colon, prostate, and small cell lung carcinomas

49. HYPERCALCEMIA CLINICAL FEATURES- GENERAL- dehydration,weight loss,anorexia,polydipsia NEUROMUSCULAR- fatigue,lethargy,muscle weakness,hyporeflexia,confusion,psychosis , seizure,coma . GASTROINTESTINAL- nausea,vomiting,constipation,ileus GENITORENAL- polyurea,renal insufficiency CARDIAC- bradycardia,prolonged P-R intervel,shortened Q-T interval,wide T wave,atrial or ventricular arrhythmias.

50. HYPERCALCEMIA PATHOPHYSIOLOGY- 1. Parathyroid Hormone and the Parathyroid Hormone–Related Protein- Many patients with cancer-related hypercalcemia have biochemical characteristics suggestive of PTH stimulation, including increased tubular reabsorption of calcium, hypophosphatemia with phosphaturia , and elevated levels of nephrogenous cyclic adenosine monophosphate

51. HYPERCALCEMIA PTH-RP appears to be the most common mediator of cancer-related hypercalcemia . Increased blood levels of PTH-RP are commonly found in patients with solid tumors , particularly patients with squamous ( epidermoid ) carcinomas. Several studies have shown that patients with high levels tend to have an inferior response when treated with bisphosphonates and a poorer life expectancy

52. HYPERCALCEMIA Vitamin D3- Elevated serum 1,25 (OH)2-vitamin D3 levels have been reported in patients with Hodgkin's disease, non-Hodgkin's lymphoma, myeloma, and occasional patients with solid tumors . This effect probably results from increased enzymatic conversion of 25-OH-vitamin D 3 by 1a-vitamin D- hydroxylase , similar to well-documented processes that occur in patients with granulomatous disease.

53. HYPERCALCEMIA Prostaglandins- Prostaglandins have long been implicated as circulating mediators of cancer-related hypercalcemia , and certain prostaglandins (notably of the E series) have potent bone- resorptive activity in vitro Cytokines- TGF-a shares partial amino acid homology with epidermal growth factor, binds to the epidermal growth factor receptor, and is a potent inducer of bone resorption in vitro, both alone and in combination with PTH-RP. Interleukin-6 increases bone resorption in vitro, acts as an autocrine growth factor in myeloma, and may be associated with hypercalcemia in kidney cancer.

54. HYPERCALCEMIA TREATMENT OF CANCER-RELATED HYPERCALCEMIA- Where possible, immobilization should be minimized because inactivity tends to aggravate hypercalcemia Patients should be carefully interviewed with respect to dietary aberrations, and medications containing calcium, vitamin D, vitamin A, or other retinoids should be stopped. Intravenous Fluids and Diuretics , this approach is outdated Most patients benefit substantially from the early introduction of specific antihypercalcemic therapy, and this approach leads to more rapid clinical improvement, lower overall toxicity, and decreased cost.

55. HYPERCALCEMIA SPECIFIC MEASURES- Intravenous Fluids and Diuretics- Assuming renal and cardiac functions are adequate, saline infusion at a rate of 300 to 400 or more mL /h can be used for 3 to 4 hours in severely dehydrated patients. Slower hydration is indicated for less severe disturbances or in patients with congestive heart failure or oliguria Such treatment is excessively toxic since it frequently causes fluid overload and occasionally life-threatening pulmonary edema . The resulting weight gain and lower extremity edema that occurs in hypoproteinemic patients with advanced cancer may not resolve during the life of that individual and can be severely disabling.

56. HYPERCALCEMIA Furosemide also increases the risk for developing hypovolemia ; the resultant decrease in glomerular filtration may actually stimulate renal calcium reabsorption , inadvertently reinduce dehydration, and worsen the clinical condition.

57. HYPERCALCEMIA Bisphosphonates - Bisphosphonates adsorb to the surface of crystalline hydroxyapatite and inhibit calcium release from bone by interfering with the metabolic activity of osteoclasts . There are numerous bisphosphonates available or undergoing clinical investigation, including etidronate , clodronate , pamidronate , zoledronate , alendronate , tiludronate , ibandronate , and risedronate . Bisphosphonates have low oral bioavailability (less than 1%), and none of these agents is currently recommended as an oral therapy for hypercalcemia

58. HYPERCALCEMIA Intravenous pamidronate has become the most widely prescribed drug for treatment of hypercalcemia . This drug is well-tolerated and its side effects are usually limited to infusion-site irritation, fever, and flu-like symptoms that occur after the first infusion in approximately 20% of patients. Although multiple doses and schedules have been tested, pamidronate is most commonly given at doses of 60 or 90 mg infused over 2 hours.

59. HYPERCALCEMIA Gallium Nitrate- Gallium nitrate is a potent inhibitor of bone resorption . Elemental gallium is incorporated into bone and renders hydroxyapatite less soluble and more resistant to cell-mediated resorption . Following administration as a continuous intravenous infusion (200 mg/m 2/d over 24 hours for up to 5 days), gallium nitrate induces normocalcemia in 70% to 90% of patients.

60. HYPERCALCEMIA Calcitonin - Pharmacologic doses of calcitonin reduce serum calcium by increasing renal calcium excretion and inhibiting bone resorption . Calcitonin is especially advantageous due to its rapid onset of action (2 to 4 hours). High doses of calcitonin (6 to 8 IU/kg every 6 hours) should be employed for acute treatment of hypercalcemia

61. HYPERCALCEMIA CORTICOSTEROIDS- Corticosteroids acutely inhibit osteoclast -mediated bone resorption in vitro and decrease gastrointestinal calcium resorption . Prednisone (40 to 100 mg/d or its equivalent) is usually effective in controlling hypercalcemia caused by hematologic cancers; lower doses (15 to 30 mg/d) may suffice for patients with hypercalcemic flares caused by breast cancer.

62. HYPERCALCEMIA Phosphates- An increase in serum phosphorus concentration decreases osteoclastic activity, inhibits calcium resorption from bone, and causes a significant reduction in urinary calcium excretion. Oral phosphate (0.5 to 3.0 g/d) may be highly effective, particularly in mild forms of hypercalcemia

63. HYPERCALCEMIA Plicamycin - Plicamycin (formerly mithramycin ) induces hypocalcemia by a direct cytotoxic effect on osteoclasts , thereby decreasing cell-mediated bone resorption . Plicamycin is administered at doses ranging from 10 to 50 μg /kg of body weight. The usual dose is 25 μg /kg or a total dose of 1.5 to 2.0 mg given as a brief infusion. Since the onset of action occurs after 24 to 48 hours, doses should not be repeated more frequently than every 2 days

64. TUMOR LYSIS SYNDROME The tumor lysis syndrome occurs as a result of the rapid release of intracellular contents into the blood stream, which then increase to life-threatening concentrations. The syndrome is characterized by hyperuricemia , hyperkalemia , hyperphosphatemia , and hypocalcemia . Lethal cardiac arrhythmias are the most serious consequences of hyperkalemia . Hyperphosphatemia may result in acute renal failure. Elevated serum phosphorus may also decrease renal function, which can lead to further reductions in urinary potassium and phosphate excretion. Hypocalcemia , a result of hyperphosphatemia , may cause muscle cramps, cardiac arrhythmias, and tetany .

65. TUMOR LYSIS SYNDROME Tumor lysis : definition Cairo-Bishop • Lab: 2 or more – Uric acid >8 – K >6 – Phos >4.5 – Calcium <7 • Clinical – Lab + creat > 1.5 x ULN – Cardiac arrhythmia/sudden death – Seizure

66. TUMOR LYSIS SYNDROME The tumor lysis syndrome occurs most commonly in diseases with large tumor burdens and high proliferative fractions that are exquisitely sensitive to cytotoxic treatment. These disorders include high-grade lymphomas, leukemias with high leukocyte counts, and (much less commonly) solid tumors . The syndrome has been observed not only with agents that have potent myelosuppressive activity, but also with drugs such as interferon-a, tamoxifen , cladribine , and intrathecal methotrexate

67. TUMOR LYSIS SYNDROME Treatment should be preventive! Chemotherapy should be delayed until all metabolic abnormalities are corrected Ideally patients should be pretreated with allopurinol and high rate hydration with IV Fluids. Urine may be alkalinized as well In patients with active tumor lysis , High Rate IV Fluids, allopurinol and holding chemotherapy are the initial steps If severe electrolytes abnormalities are present (or life-threatening hyperkalemia ), hemodyalisis should be instituted immediately

68. TUMOR LYSIS SYNDROME Management- Prophylaxis Pre-treat for at least 2 days before chemotherapy with: Allopurinol Aggressive hydration (with NS) to maintain urine output > 2.5L/day Alkalinization is no longer recommended as it can enhance calcium/phosphate deposition

69. TUMOR LYSIS SYNDROME Once therapy has begun Check lytes , Ca, Mg, Po4 BID until stable Phosphate binders: lower serum phos either with calcium carbonate (taken with meals) or aluminum based binders ( amphogel , alternagel ) Kayexalate for hyperkalemia Dialysis when required

70. TUMOR LYSIS SYNDROME Consider dialysis for Potassium > 7 Uric Acid > 10 PO4 > 10 Hypertension Volume overload Other symptomatic electrolyte abnormalities

71. SIADH Inappropriate or ectopic secretion of ADH – Tumors 40% of small cell lung cancer pt (poor prognosis) – Cytotoxic agents Vincristine , cyclophosphamide , cisplatin – Drug, fluids to prevent cystitis – brain lesions, narcotics

72. SIADH Mild symptoms include weakness, muscle cramps, loss of appetite, and fatigue; serum sodium levels range from 115 to 120mEq/L More serious signs and symptoms relate to water intoxication and include weight gain, personality changes, confusion, and extreme muscle weakness As the serum sodium level approaches 110mEq/L seizures, coma, and eventually death will occur, unless the condition is rapidly treated

73. SIADH TREATMENT- initiate fluid restriction and increased sodium intake. administer demeclocycline ( Declomycin ), an antagonist to ADH Monitor serum sodium levels

74. Malignant Pericardial Effusions Seen most commonly in lung cancer, lymphoma, and breast cancers. Complicates up to 5% of cancers May require emergent pericardiocentesis for CV collapse Echocardiography confirms diagnosis of effusion

75. Malignant Pericardial Effusions Ultimate treatment is pericardial window for drainage with 0 to 15% recurrence Other definitive therapies can be done Radiation with 33% recurrence Systemic chemotherapy with 30% recurrence Pericardial sclerosis with tetracycline or bleomycin with 15 to 30% recurrence

76. Leukostasis Leukostasis is a syndrome associated with acute myelogenous leukemia (AML) and consists of respiratory distress, abnormal chest radiograph, confusion, and central nervous system bleeding. Patients may be confused or stuporous . Gingival hyperplasia or skin lesions may occur secondary to invasion of blasts in myelomonocytic (M4) and monocytic (M5) types of AML

77. Leukostasis Leukostasis is associated with high and rapidly increasing blast counts, usually more than 50K and often more than 100K. Patients in leukostasis are usually hypoxemic A nonspecific diffuse infiltrate is often present on CXR. There may be impairment of other end organs, including the eye, kidney, and liver. Lactic acidosis may be a late event. Symptoms may be fulminant , leading to death in a matter of days or even hours. These patients have a propensity for CNS bleeds after chemotherapy is begun, often in the absence of disseminated intravascular coagulation (DIC) or thrombocytopenia.

78. Leukostasis TREATMENT- Prompt initiation of leukapheresis can be lifesaving for these patients and should not be delayed. Leukapheresis can attenuate or reverse the symptoms of leukostasis , and patients who receive leukapheresis have a decreased incidence of CNS bleeds after beginning chemotherapy. Hydroxyurea might be considered as an adjunct to leukapheresis to decrease cell proliferation before definitive treatment. Intravenous hydration is beneficial.

79. HYPERVISCOSITY SYNDROME Clinical Features Marked elevations in serum proteins can cause an increase in serum viscosity. This can produce sludging of blood flow and a reduction of microcirculatory perfusion. The most common cause of hyperviscosity syndrome is macroglobulinemia due to multiple myeloma. Early symptoms include fatigue, headache, and somnolence. As viscosity increases, microthromboses occur and patients may develop visual disturbances, deafness, seizures, or coma.

80. HYPERVISCOSITY SYNDROME Emergency physicians must suspect this syndrome in patients with unexplained stupor or coma. The most specific physical exam findings are in the ocular fundi and include “sausage-linked” retinal vessels, hemorrhages , and exudates. A clue may be provided if the laboratory is unable to run chemistry tests due to “too thick” blood. Patients often are anemic with rouleau formation noted on peripheral blood smear. Measurement of serum viscosity and protein electrophoresis are diagnostic. Initial therapy is IV normal saline (1 to 2 L) and emergency plasmapheresis . When coma is present and the diagnosis has been rapidly established, phlebotomy (2 U) with saline infusion and replacement of patients' red blood cells may be used as a temporizing measure until plasmapheresis can be performed.

81. POLYCYTHEMIA AND LEUKOCYTOSIS An elevated hematocrit ( polycythemia ) can be due to primary overproduction of red blood cells by the bone marrow ( polycythemia vera ) or as a paraneoplastic syndrome associated with renal cell carcinoma and hepatomas . Patients can develop symptoms such as headache, fatigue, blurred vision, and thrombotic complications such as stroke or mesenteric ischemia. Both acute and chronic leukemias can produce WBCs, >100,000/ μL . Leukocytosis to this degree can impair circulation and cause symptoms such as headache, confusion, and dyspnea . The treatment of choice in patients with symptomatic polycythemia is phlebotomy (approximately 500 mL ). Treatment of symptomatic leukocytosis is by emergent leukapheresis and chemotherapy.

82. Carcinomatous Meningitis Direct or hematogenous seeding of meninges Suspect it if patient has headache or cranial neuropathy Chin numbness is the classic symptom Diplopia is most common complaint Order of frequency: acute leukemias , NHL, small cell lung, breast, and prostate cancer. Usually a late finding in heavily pre-treated patients.

83. Carcinomatous Meningitis Supportive care, steroids if intent is palliative and patient has minimal symptoms. Intrathecal chemotherapy Methotrexate Radiation therapy Systemic high dose methotrexate on the order of 4 to 5 grams with leucovorin rescue

84. HYPOGLYCEMIA Mesenchymal tumors ( fibrosarcomas , leiomyomas , rhabdomyosarcomas , liposarcomas , and mesotheliomas ) account for approximately 50% of cases; another 25% are hepatomas . Classic symptoms of hypoglycemia (e.g., weakness, dizziness, diaphoresis, and nausea) are nonspecific and may develop slowly. In the initial phases, symptoms tend to be worse in the early morning (due to overnight fasting) and improve after ingestion of food. Patients may also present acutely with seizures, coma, and focal or diffuse neurologic deficits

85. HYPOGLYCEMIA Several etiologic mechanisms for cancer-related hypoglycemia have been proposed: (1) secretion of insulin-like substances; (2) excessive glucose use by the tumor that exceeds hepatic production; (3) failure of counterregulatory mechanisms that usually prevent hypoglycemia (e.g., reduction in levels of growth hormone). Accelerated glucose use by large tumors may also account for cancer-related hypoglycemia in some patients. It has been estimated that a 1-kg tumor may use from 50 to 200 g of glucose per day.

86. HYPOGLYCEMIA Many patients with hypoglycemia have tumors that weigh several kilograms along with extensive hepatic metastases; thus, the combination of accelerated glucose use with impaired production may lead to hypoglycemia . A failure of the usual counterregulatory mechanisms in patients with large tumors may also induce hypoglycemia .

87. HYPOGLYCEMIA Mild hypoglycemia can usually be managed by increasing the frequency of meals. In patients with more severe or unpredictable symptoms, the administration of corticosteroids and glucagon may afford symptomatic relief. Intravenous infusions of glucose provide temporary support while other specific treatment is administered (i.e., surgery, chemotherapy, or radiation)

88. HYPERURICEMIA Renal complications and arthritis are the most important consequences of acute or chronic hyperuricemia . The disorder occurs most commonly in hematologic neoplasms , particularly the leukemias , high-grade lymphomas, and myeloproliferative diseases. Patients at highest risk include those with bulky high-grade lymphomas, patients with high leukocyte counts undergoing remission-induction chemotherapy for acute or chronic leukemia , and individuals with preexisting renal impairment (especially those with ureteral obstruction). Hyperuricemia is also a side effect of certain agents, notably diuretics ( thiazides and furosemide ), and antituberculosis drugs ( pyrazinamide , ethambutol ).

89. HYPERURICEMIA TREATMENT- Decrease production – allopurinol , Rasburicase Promote solubility – alkalinization (goal urine pH 7.0-7.5) Reduce concentration – volume expansion with IVF

90. ADRENAL FAILURE Symptomatic adrenocortical insufficiency due to destruction of cortical tissue by metastatic carcinoma is uncommon. More common are iatrogenic causes such as surgical adrenalectomy , treatment with mitotane and inhibitors of steroid synthesis such as aminoglutethimide , chronic corticosteroid therapy, and occasionally adrenal hemorrhage

91. ADRENAL FAILURE Classic signs and symptoms of adrenal insufficiency include weakness, weight loss, anorexia, hyperpigmentation , and postural hypotension. One or more of these symptoms are evident in almost all patients, but the onset of symptoms is frequently insidious. Circulatory collapse and shock are uncommon but may develop with the onset of infection. Biochemical evaluation frequently reveals a mild acidosis (without an anion gap), hyponatremia , and hypokalemia .

92. ADRENAL FAILURE Physiologic glucocorticoid replacement is attained by administration of cortisone acetate (25 mg in the morning and 12.5 mg in the early evening). During periods of stress (e.g., operative procedures or infection), these doses may need to be doubled or tripled. Occasionally, mineralocorticoid replacement (0.05 to 0.1 mg of fludrocortisone ) is required in addition to cortisone acetate.

93. ADRENAL FAILURE In patients with no adrenocortical function whatsoever, maintenance doses of dexamethasone or prednisone do not provide adequate mineralocorticoid coverage and fludrocortisone must be given. Pharmacologic doses of parenteral glucocorticoids are required in the setting of acute adrenal failure and circulatory collapse. Typically, aqueous-soluble forms of hydrocortisone (e.g., sodium succinate salt) at doses of 100 mg intravenously every 8 hours are required.

94. Thank You