Oncological EmergenciesOncological Emergencies

CASE 1…CASE 1…

On Physical ExaminationOn Physical Examination

Inspection:Inspection:

Mr. SVMr. SV 65 year old male 65 year old male

CAD and emphysemaCAD and emphysema

– present to clinic with one week present to clinic with one week history of increasing SOBhistory of increasing SOB

– 3 month history of weight loss, 3 month history of weight loss, decreased appetite, a change in his decreased appetite, a change in his chronic cough, and intermittent chronic cough, and intermittent hemoptysis hemoptysis

Respiratory ExaminationRespiratory Examination

StridorStridor

Dullness to percussion on right lower lung Dullness to percussion on right lower lung fieldsfields

Increased tactile fremitus to right lower Increased tactile fremitus to right lower lung fieldslung fields

Decreased A/E to right lower lung fieldsDecreased A/E to right lower lung fields

Chest X-Ray…Chest X-Ray…

right pleural effusion

ThoracentesisThoracentesis ExudateExudate

Gram stain Gram stain – NegativeNegative

AFB stainAFB stain– NegativeNegative

CytologyCytology– non-small cell lung cancernon-small cell lung cancer

Large cell typeLarge cell type

T1-weighted axial MRI demonstrating T1-weighted axial MRI demonstrating paratracheal soft tissue mass that invades into paratracheal soft tissue mass that invades into the SVCthe SVC

Superior Vena Cava Superior Vena Cava SyndromeSyndrome

DefinitionDefinition

Obstruction of blood flow in the superior Obstruction of blood flow in the superior vena cava results in signs and vena cava results in signs and symptoms of SVC syndromesymptoms of SVC syndrome

EtiologyEtiology

Caused by either invasion or Caused by either invasion or external compression of the SVC external compression of the SVC by contiguous pathologic processby contiguous pathologic process

Right lung pathology, lymph Right lung pathology, lymph nodes, other mediastinal nodes, other mediastinal structures, or thrombosisstructures, or thrombosis

EtiologyEtiology

Before antibiotics the most Before antibiotics the most common causes were from common causes were from complications of untreated complications of untreated infectioninfection– Syphilitic thoracic aneurysmsSyphilitic thoracic aneurysms– fibrosing mediastinitisfibrosing mediastinitis

Malignancy is presently the most Malignancy is presently the most common causecommon cause

Symptoms and SignsSymptoms and Signs As the obstruction develops venous As the obstruction develops venous

collaterals are formedcollaterals are formed Symptom onset depends on speed of Symptom onset depends on speed of

SVC obstruction onsetSVC obstruction onset Malignant disease can arise in weeks Malignant disease can arise in weeks

to monthsto months– Not enough time to develop Not enough time to develop

collateralscollaterals Fibrosing mediastinitis can take years Fibrosing mediastinitis can take years

to have symptomsto have symptoms

Symptoms and SignsSymptoms and Signs Central venous pressures remain high Central venous pressures remain high

even in collateralseven in collaterals– High pressures cause the High pressures cause the

characteristic clinical picturecharacteristic clinical picture

Shortness of breath is the most Shortness of breath is the most common symptomcommon symptom11

1. Parish, JM, Marschke, RF Jr, Dines, DE, Lee, RE. Etiologic 1. Parish, JM, Marschke, RF Jr, Dines, DE, Lee, RE. Etiologic considerations in superior vena cava syndrome. Mayo Clin Proc 1981; considerations in superior vena cava syndrome. Mayo Clin Proc 1981; 56:407. 56:407.

Signs and SymptomsSigns and Symptoms

Facial swelling or head fullnessFacial swelling or head fullness– exacerbated by bending forward or lying exacerbated by bending forward or lying

downdown

CoughCough

Arm edemaArm edema

CyanosisCyanosis

Facial swelling associated with SVC Facial swelling associated with SVC Syndrome in a patient with malignancySyndrome in a patient with malignancy

Physical FindingsPhysical Findings

Venous distension Venous distension – neckneck– chest wallchest wall

Facial EdemaFacial Edema

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

Etiology: MalignancyEtiology: Malignancy Lung cancer is the most commonLung cancer is the most common22

Lymphoma is second most commonLymphoma is second most common

together represent 94% of casestogether represent 94% of cases

2. Escalante, CP. Causes and management of superior vena 2. Escalante, CP. Causes and management of superior vena cava syndrome. Oncology (Huntingt) 1993; 7:61.cava syndrome. Oncology (Huntingt) 1993; 7:61.

NSCLCNSCLC 2-4% of bronchogenic cancer patients 2-4% of bronchogenic cancer patients

develop SVC syndromedevelop SVC syndrome

extrinsic compression or direct invasionextrinsic compression or direct invasion– primary tumor or by enlarging primary tumor or by enlarging

mediastinal nodesmediastinal nodes

3. Armstrong, BA, Perez, CA, Simpson, JR, Hederman, MA. 3. Armstrong, BA, Perez, CA, Simpson, JR, Hederman, MA. Role of irradiation in the management of superior vena cava Role of irradiation in the management of superior vena cava syndrome. Int J Radiat Oncol Biol Phys 1987; 13:531.syndrome. Int J Radiat Oncol Biol Phys 1987; 13:531.

Small Cell Lung CancerSmall Cell Lung Cancer

Greatest riskGreatest risk

20% will develop SVC obstruction20% will develop SVC obstruction

more common because SCLC tends to more common because SCLC tends to occur centrally in contrast to other occur centrally in contrast to other typestypes

LymphomaLymphoma 2-4% of patients2-4% of patients

predominantly non-Hodgkin’s lymphomapredominantly non-Hodgkin’s lymphoma44

Hodgkin’s rarely causes SVC syndromeHodgkin’s rarely causes SVC syndrome

4. Perez-Soler, R, McLaughlin, P, Velasquez, WS, et al. Clinical 4. Perez-Soler, R, McLaughlin, P, Velasquez, WS, et al. Clinical features and results of management of superior vena cava features and results of management of superior vena cava syndrome secondary to lymphoma. J Clin Oncol 1984; 2:260.syndrome secondary to lymphoma. J Clin Oncol 1984; 2:260.

LymphomaLymphoma

Extrinsic compression caused by Extrinsic compression caused by enlarging lymph nodesenlarging lymph nodes

Other cancersOther cancers ThymomaThymoma

primary mediastinal germ cell neoplasmprimary mediastinal germ cell neoplasm

solid tumors with mediastinal nodal solid tumors with mediastinal nodal metastasesmetastases

breast cancer most common typebreast cancer most common type

Other causesOther causes

Post radiation local vascular fibrosis can Post radiation local vascular fibrosis can also be considered in oncology patientsalso be considered in oncology patients

Thoracic radiation treatment may Thoracic radiation treatment may predate syndrome by many yearspredate syndrome by many years

Other causesOther causes ThrombosisThrombosis

Indwelling central venous cathetersIndwelling central venous catheters

5. Sivaram, CA, Craven, P, Chandrasekaran, K. Transesophageal 5. Sivaram, CA, Craven, P, Chandrasekaran, K. Transesophageal echocardiography during removal of central venous catheter echocardiography during removal of central venous catheter associated with thrombus in superior vena cava. Am J Card Imaging associated with thrombus in superior vena cava. Am J Card Imaging 1996; 10:266. 1996; 10:266.

DiagnosisDiagnosis Timely identification of the cause is Timely identification of the cause is

essentialessential

Radiographic studies are usefulRadiographic studies are useful

Up to 60% of patients with SVC syndrome Up to 60% of patients with SVC syndrome related to neoplasm do not have a known related to neoplasm do not have a known diagnosis of cancerdiagnosis of cancer66

– Need a tissue biopsy for histologic Need a tissue biopsy for histologic studiesstudies

6. Schraufnagel, DE, Hill, R, Leech, JA, Pare, JA. Superior vena caval 6. Schraufnagel, DE, Hill, R, Leech, JA, Pare, JA. Superior vena caval obstruction. Is it a medical emergency?. Am J Med 1981; 70:1169. obstruction. Is it a medical emergency?. Am J Med 1981; 70:1169.

Radiographic StudiesRadiographic Studies

Most patients have an abnormal chest Most patients have an abnormal chest x-ray at presentationx-ray at presentation

Most common findings areMost common findings are– Mediastinal wideningMediastinal widening– Pleural effusionPleural effusion

CT ChestCT Chest

Preferred choicePreferred choice

IV contrast IV contrast – defines the level of obstructiondefines the level of obstruction– maps out collateral pathwaysmaps out collateral pathways– can identify underlying cause of can identify underlying cause of

obstructionobstruction

MRIMRI

Can be useful in patients with IV Can be useful in patients with IV contrast allergiescontrast allergies

Same patient’s MRI to further define the Same patient’s MRI to further define the intramural massintramural mass

Histologic DiagnosisHistologic Diagnosis

EssentialEssential

Guides treatmentGuides treatment

Aids in defining prognosisAids in defining prognosis

Treatment of Oncologic Treatment of Oncologic CausesCauses

TreatmentTreatment

Aimed at underlying causeAimed at underlying cause

Evolution of thought has occurred in Evolution of thought has occurred in recent yearsrecent years

Historically SVC syndrome was Historically SVC syndrome was considered a potentially life-considered a potentially life-threatening emergencythreatening emergency

Standard of care was immediate Standard of care was immediate radiotherapyradiotherapy

The emergent approach is not The emergent approach is not appropriate for most patientsappropriate for most patients

Newer Newer strategiesstrategies

Emergent to UrgentEmergent to Urgent

Symptomatic obstruction is usually a Symptomatic obstruction is usually a prolonged processprolonged process

Most patients are not in immediate Most patients are not in immediate danger at presentationdanger at presentation

Most have time for a full diagnostic Most have time for a full diagnostic work upwork up

Emergent to UrgentEmergent to Urgent

Prebiopsy radiation can obscure the Prebiopsy radiation can obscure the diagnosisdiagnosis

Current strategies aim at accurate Current strategies aim at accurate diagnosis of underlying etiology before diagnosis of underlying etiology before therapytherapy

ExceptionException to new rule to new rule

StridorStridor Central airway obstruction or Central airway obstruction or

laryngeal edemalaryngeal edema True medical emergencyTrue medical emergency Immediate action neededImmediate action needed

Possible intubation and ICU admissionPossible intubation and ICU admission Immediate therapy to target Immediate therapy to target

obstruction neededobstruction needed

Prognosis…Prognosis…

Linked to tumor histology and Linked to tumor histology and stage at presentationstage at presentation

Treatment Sensitive Treatment Sensitive TumorsTumors

NHLs, germ cells, and limited-stage NHLs, germ cells, and limited-stage small cell lung cancers usually respond small cell lung cancers usually respond to chemotherapy and or radiationto chemotherapy and or radiation

Can achieve long term remission with Can achieve long term remission with tumor specific directed therapytumor specific directed therapy

Symptomatic improvement usually Symptomatic improvement usually takes 1-2 weeks after start of therapytakes 1-2 weeks after start of therapy

Note: Note: CorticosteroidsCorticosteroids Controversial issue with regards Controversial issue with regards

to treatment benefit at to treatment benefit at presentationpresentation

Non-small cell lung cancerNon-small cell lung cancer

SVC obstruction is a strong predictor SVC obstruction is a strong predictor of poor prognosisof poor prognosis

Median survival around 5 monthsMedian survival around 5 months77

Choice of therapy considers likelihood Choice of therapy considers likelihood of response to each modalityof response to each modality

7. Martins, SJ, Pereira, JR. Clinical factors and prognosis in non-7. Martins, SJ, Pereira, JR. Clinical factors and prognosis in non-small cell lung cancer. Am J Clin Oncol 1999; 22:453. small cell lung cancer. Am J Clin Oncol 1999; 22:453.

Intraluminal StentsIntraluminal Stents Endovascular placement under Endovascular placement under

fluoroscopyfluoroscopy

Patients who have recurrent disease Patients who have recurrent disease in previously irradiated fieldsin previously irradiated fields

Tumors refractory chemotherapyTumors refractory chemotherapy

Patient too ill to tolerate radiation or Patient too ill to tolerate radiation or chemotherapychemotherapy

Intraluminal StentsIntraluminal Stents

Some data suggests benefit from Some data suggests benefit from immediate stent placement in NSCLC immediate stent placement in NSCLC at presentationat presentation88

Tends to provide more rapid relief of Tends to provide more rapid relief of symptomssymptoms

Issue of anticoagulation after is not Issue of anticoagulation after is not resolvedresolved8. Rowell, NP, Gleeson, FV. Steroids, radiotherapy, 8. Rowell, NP, Gleeson, FV. Steroids, radiotherapy,

chemotherapy and stents for superior vena caval obstruction in chemotherapy and stents for superior vena caval obstruction in carcinoma of the bronchus: a systematic review. Clin Oncol (R carcinoma of the bronchus: a systematic review. Clin Oncol (R Coll Radiol) 2002; 14:338. Coll Radiol) 2002; 14:338.

CASE 2…CASE 2…

Mr. ECMr. EC 56 year old man with history of HTN 56 year old man with history of HTN

and osteoarthrtisand osteoarthrtis

presents to family doctor with one presents to family doctor with one month history of back pain that is not month history of back pain that is not responding to pain killers. responding to pain killers.

On examinationOn examination vitals stable, no fevervitals stable, no fever

CVS, Respiratory, GI, GU exams reported as CVS, Respiratory, GI, GU exams reported as normalnormal

Back examBack exam– Inspection: normalInspection: normal– Palpation: some pain in L1Palpation: some pain in L1– ROM: normalROM: normal– Some pain in right leg with straight leg Some pain in right leg with straight leg

raisingraising

Investigation in ClinicInvestigation in Clinic

Lumbar Spine X-rayLumbar Spine X-ray– Some age related degenerationSome age related degeneration

DiagnosisDiagnosis

Sciatica vs. Back strainSciatica vs. Back strain

Treatment: Treatment: – NSAIDSNSAIDS– Few days of bed restFew days of bed rest

The story continues…The story continues…

Mr. EC’s pain does not resolveMr. EC’s pain does not resolve

More trials of various forms of pain control More trials of various forms of pain control failfail

One month later Mr. EC awakens in the One month later Mr. EC awakens in the morning and has difficulty supporting his morning and has difficulty supporting his weightweight– Subjective leg muscle weaknessSubjective leg muscle weakness

Goes to Emergency roomGoes to Emergency room

In ERIn ER Patient has objective leg weakness on Patient has objective leg weakness on

physical examphysical exam

A very keen medical student does a rectal A very keen medical student does a rectal exam and discovers a large nodular exam and discovers a large nodular prostateprostate

PSA: 45.0PSA: 45.0

MRI Spine…..MRI Spine…..

Spinal Cord CompressionSpinal Cord Compression

Malignant Epidural Spinal Cord Malignant Epidural Spinal Cord Compression (ESCC)Compression (ESCC)

Neoplastic invasion of the space between Neoplastic invasion of the space between vertebrae and spinal cord (epidural invasion)vertebrae and spinal cord (epidural invasion)– Usually from bone metastasesUsually from bone metastases

Compresses thecal sac of spinal cordCompresses thecal sac of spinal cord

Frequent complication of malignancyFrequent complication of malignancy

Can cause painCan cause pain

Can cause irreversible loss of neurologic Can cause irreversible loss of neurologic functionfunction

DefinitionDefinition

Any radiological indentation of the Any radiological indentation of the thecal sac thecal sac

Tip of the spinal cord lies at the L1 Tip of the spinal cord lies at the L1 vertebral levelvertebral level

Lumbosacral nerve roots form the cauda Lumbosacral nerve roots form the cauda equinaequina

EpidemiologyEpidemiology

Many cases of unrecognized ESCCMany cases of unrecognized ESCC

Difficult to define incidenceDifficult to define incidence

Autopsy review studies suggest around 5% Autopsy review studies suggest around 5% of cancer patients die with ESCCof cancer patients die with ESCC

CausesCauses Metastatic tumor from any primary siteMetastatic tumor from any primary site

Tumors with predilection to metastasize to Tumors with predilection to metastasize to spinal columnspinal column

Prostate, breast, and lung carcinomaProstate, breast, and lung carcinoma– 15-20% of cases15-20% of cases

Renal cell, non-Hodgkin’s lymphoma, or Renal cell, non-Hodgkin’s lymphoma, or myelomamyeloma– 5-10% of cases5-10% of cases

Vertebral metastases are more common than Vertebral metastases are more common than ESCCESCC

– Prostate cancer: 90%Prostate cancer: 90%

– Breast Cancer: 74%Breast Cancer: 74%

– Lung Cancer: 45%Lung Cancer: 45%

– Lymphoma: 29%Lymphoma: 29%

– Renal cell: 29%Renal cell: 29%

– GI: 25%GI: 25%

10. Posner, JB. Neurologic Complications of Cancer. FA Davis, 10. Posner, JB. Neurologic Complications of Cancer. FA Davis, Philadelphia, 1995 Philadelphia, 1995

ESCC can be initial presentation of a ESCC can be initial presentation of a malignancymalignancy– Around 20% of casesAround 20% of cases– In many cases diagnosis is made by In many cases diagnosis is made by

biopsy of the spinal lesionbiopsy of the spinal lesion

Spinal LocationSpinal Location

Thoracic spine: 60%Thoracic spine: 60%

Lumbosacral spine: 30%Lumbosacral spine: 30%

Cervical spine: 10%Cervical spine: 10%

Specific tumor predilection is difficult to Specific tumor predilection is difficult to definedefine

Clinical FeaturesClinical Features

Important to recognizeImportant to recognize

Early recognition leads to better outcomesEarly recognition leads to better outcomes

Efficacy of treatment depends most on Efficacy of treatment depends most on patient’s neurological function at patient’s neurological function at presentationpresentation

Median time from symptoms to diagnosis is Median time from symptoms to diagnosis is around 2 months in 1998around 2 months in 19981111

More than half of patients who present to More than half of patients who present to hospital are non-ambulatoryhospital are non-ambulatory

11. Husband, DJ. Malignant spinal cord compression: Prospective 11. Husband, DJ. Malignant spinal cord compression: Prospective study of delays in referral and treatment. BMJ 1998; 317:18. study of delays in referral and treatment. BMJ 1998; 317:18.

RED RED FLAGS…..FLAGS…..

First Red Flag: First Red Flag: PainPain

Usually first symptomUsually first symptom– 80-90% of the time80-90% of the time

Usually precedes other neurologic Usually precedes other neurologic symptoms by seven weekssymptoms by seven weeks– Increases in intensityIncreases in intensity

Severe local back painSevere local back pain Aggravated by recumbencyAggravated by recumbency

– Distension of venous plexusDistension of venous plexus May become radicularMay become radicular

Second Red Flag: Second Red Flag: MotorMotor Weakness: 60-85%Weakness: 60-85%

Patients may be hyperreflexic below the Patients may be hyperreflexic below the lesion and have extensor plantarslesion and have extensor plantars

Weakness tends to be symmetricalWeakness tends to be symmetrical

Progressive weakness is followed by lost of Progressive weakness is followed by lost of gait function then paralysisgait function then paralysis

The severity of weakness is greatest with The severity of weakness is greatest with thoracic metastasesthoracic metastases

Third Red Flag: Third Red Flag: SensorySensory Less common than motor findingsLess common than motor findings

Still present in majority of casesStill present in majority of cases

Ascending numbness and parathesiasAscending numbness and parathesias

Fourth Red Flag: Fourth Red Flag: Bladder Bladder and Bowel Functionand Bowel Function

Loss is late findingLoss is late finding

Autonomic neuropathy presents usually Autonomic neuropathy presents usually as urinary retensionas urinary retension

Rarely sole findingRarely sole finding

Radiologic Radiologic InvestigationInvestigation

Entire imaging of spine is idealEntire imaging of spine is ideal

– Focused CT imaging can miss clinically Focused CT imaging can miss clinically unapparent lesionsunapparent lesions

Myelography and MRI are better than plain Myelography and MRI are better than plain X-Rays, bone scans and CT for diagnosisX-Rays, bone scans and CT for diagnosis

MRIMRI

Intramedullary Intramedullary MetastasesMetastases Less commonLess common

Often present with hemicord symptomsOften present with hemicord symptoms Unilateral weakness below lesionUnilateral weakness below lesion Contralateral diminution of pain and Contralateral diminution of pain and

temperature sensationtemperature sensation Can progress to bilateral dysfunctionCan progress to bilateral dysfunction

Radiation MyelopathyRadiation Myelopathy

Can mimic ESCCCan mimic ESCC

MR imaging can make distinctionMR imaging can make distinction

TreatmentTreatment

Treatment delays…….Treatment delays…….

2 month median delay in treatment 2 month median delay in treatment from onset of back painfrom onset of back pain

14 day delay in treatment from onset of 14 day delay in treatment from onset of neurological symptomsneurological symptoms

Why the delay?Why the delay?

Patient factorsPatient factors

General practitioner factorsGeneral practitioner factors

Hospital factorsHospital factors

EDUCATIONEDUCATION

Treatment ObjectivesTreatment Objectives

Pain controlPain control

Avoidance of complicationsAvoidance of complications

Preserve or improve neurological Preserve or improve neurological functionfunction

Pain managementPain management

CorticosteroidsCorticosteroids Decrease edemaDecrease edema

OpiatesOpiates Needed to decrease pain for comfort and Needed to decrease pain for comfort and

examination purposesexamination purposes

Radiation TherapyRadiation Therapy

Definitive choiceDefinitive choice

Centered on spineCentered on spine

Extends one to two vertebral bodies above Extends one to two vertebral bodies above and below the epidural metastasisand below the epidural metastasis

SurgerySurgery

Within 48 hoursWithin 48 hours

Improvement in surgery+radsImprovement in surgery+rads– Days remained ambulatory (126 vs. Days remained ambulatory (126 vs.

35)35)– Percent that regained ambulation Percent that regained ambulation

after therapy (56% vs. 19%)after therapy (56% vs. 19%)– Days remained continent (142 vs. 12)Days remained continent (142 vs. 12)– Less steroid dose, less narcoticsLess steroid dose, less narcotics– Trend to increase survivalTrend to increase survival

ChemotherapyChemotherapy Can be successful in chemosensitive tumorsCan be successful in chemosensitive tumors

– Hodgkin’s lymphomaHodgkin’s lymphoma– Non-Hodgkin’s lymphomaNon-Hodgkin’s lymphoma– NeuroblastomaNeuroblastoma– Germ cellGerm cell– Breast cancer (hormonal manipulation)Breast cancer (hormonal manipulation)– Prostate cancer (hormonal manipulation)Prostate cancer (hormonal manipulation)

BisphosphonatesBisphosphonates

RecommendedRecommended

Decrease pathologic fractures in bony Decrease pathologic fractures in bony diseasedisease– Multiple myelomaMultiple myeloma– Breast cancerBreast cancer

PrognosisPrognosis Median survival with ESCC is 6 monthsMedian survival with ESCC is 6 months1414

Ambulatory patients with radiosensitive Ambulatory patients with radiosensitive tumors have the best prognosistumors have the best prognosis

14. Sorensen, PS, Borgesen, SE, Rohde, K, et al. Metastatic epidural 14. Sorensen, PS, Borgesen, SE, Rohde, K, et al. Metastatic epidural spinal cord compression. Results of treatment and survival. Cancer spinal cord compression. Results of treatment and survival. Cancer 1990; 65:1502. 1990; 65:1502.

Treatment DelayTreatment Delay

EducationEducation

EXPERIENCEEXPERIENCE

EducationEducation

EXPERIENCEEXPERIENCE

Case 3: Mrs. HCCase 3: Mrs. HC ID:ID: 75 year old female living alone 75 year old female living alone

with no significant past medical with no significant past medical historyhistory

EC:EC: brought to ER by paramedics brought to ER by paramedics after neighbor called b/c she was after neighbor called b/c she was found in her apartment unresponsivefound in her apartment unresponsive

No collateral historyNo collateral history

ExaminationExamination Fluctuating level of consciousnessFluctuating level of consciousness

Vitals normal, no feverVitals normal, no fever

DehydratedDehydrated

Coarse upper airway soundsCoarse upper airway sounds

No other pertinent findingsNo other pertinent findings

InvestigationsInvestigations CBC normalCBC normal

Mildly elevated BUN and CrMildly elevated BUN and Cr

Normal LFTsNormal LFTs

Standard electrolytes normalStandard electrolytes normal

Concern of pneumoniaConcern of pneumonia

Chest x-ray ordered……Chest x-ray ordered……

Multiple Pulmonary MetastasisMultiple Pulmonary Metastasis

Calcium checkedCalcium checked– 4.54.5

HypercalcemiaHypercalcemia

SymptomsSymptoms

Usually nonspecificUsually nonspecific

Many times patients present with Many times patients present with very high calcium levelvery high calcium level

Most research done in Most research done in hyperparathyroidismhyperparathyroidism

GastrointestinalGastrointestinal Constipation is most commonConstipation is most common1515

– Exacerbated or confused with narcotic Exacerbated or confused with narcotic effectseffects

– Related to autonomic dysfunctionRelated to autonomic dysfunction AnorexiaAnorexia Vague abdominal painVague abdominal pain Rarely can lead to pancreatitisRarely can lead to pancreatitis

15. Heath, H 3d. Clinical spectrum of primary 15. Heath, H 3d. Clinical spectrum of primary hyperparathyroidism: Evolution with changes in medical practice hyperparathyroidism: Evolution with changes in medical practice and technology. J Bone Miner Res 1991; 6(Suppl 2):S63. and technology. J Bone Miner Res 1991; 6(Suppl 2):S63.

Renal DysfunctionRenal Dysfunction NephrolithiasisNephrolithiasis

– More common in hyperparathyroidismMore common in hyperparathyroidism Nephrogenic diabetes insipidusNephrogenic diabetes insipidus

– Defect in concentrating abilityDefect in concentrating ability– Polyuria and polydipsiaPolyuria and polydipsia

Chronic renal failureChronic renal failure– Longstanding high calciumLongstanding high calcium

Calcifcation, degeneration, and necrosis of Calcifcation, degeneration, and necrosis of tubulestubules

NeuropsychiatircNeuropsychiatirc

AnxietyAnxiety DepressionDepression Cognitive dysfunctionCognitive dysfunction

– DeleriumDelerium– PsychosisPsychosis– HallucinationsHallucinations– SomnolenceSomnolence– ComaComa

CardiovascularCardiovascular

Short QT intervalShort QT interval

Supraventricualr arrhythmiasSupraventricualr arrhythmias

Ventricular arrhythmiasVentricular arrhythmias

Physical FindingsPhysical Findings

Usually not specificUsually not specific

Dehydration secondary to diuresis Dehydration secondary to diuresis caused by the hypercalcemia caused by the hypercalcemia

Corneal deposition of calciumCorneal deposition of calcium– ““band keratopathy” on slit lamp examband keratopathy” on slit lamp exam

EpidemiologyEpidemiology

Occurs in about 10 to 20% of Occurs in about 10 to 20% of patients with cancerpatients with cancer

Both solid tumors and leukemiasBoth solid tumors and leukemias Most commonMost common

– BreastBreast– LungLung– Multiple myelomaMultiple myeloma

PathogenesisPathogenesis

Three mechanismsThree mechanisms

Osteolytic metastases with local Osteolytic metastases with local cytokine releasecytokine release

Tumor secretion of parathyroid Tumor secretion of parathyroid hormone-related protein (PTHrP)hormone-related protein (PTHrP)

Tumor production of calcitriolTumor production of calcitriol

Osteolytic MetastasesOsteolytic Metastases

DiagnosisDiagnosis

Malignancy must be ruled out in Malignancy must be ruled out in patients that present with a very patients that present with a very high calcium and no other high calcium and no other obvious causeobvious cause

TreatmentTreatment

AimsAims

Lower serum calcium Lower serum calcium concentrationconcentration

Treat complications if presentTreat complications if present

Treat underlying diseaseTreat underlying disease

VolumeVolume

Large volume of normal Saline Large volume of normal Saline administrationadministration

Expands intravascular volumeExpands intravascular volume Increases calcium excretionIncreases calcium excretion

Inhibition of Bone Inhibition of Bone ResorptionResorption

Three therapiesThree therapies– CalcitoninCalcitonin– BisphosphonatesBisphosphonates– Gallium nitrateGallium nitrate

BisphosphonatesBisphosphonates Adsorb to the surface of bone Adsorb to the surface of bone

hyroxyapatitehyroxyapatite Interfere with osteoclast activityInterfere with osteoclast activity Cytotoxic to osteoclastsCytotoxic to osteoclasts Inhibit calcium release from boneInhibit calcium release from bone Three commonly usedThree commonly used

– PamidronatePamidronate– Zoledronic acidZoledronic acid– Etidronate (1Etidronate (1stst generation, weaker) generation, weaker)

BisphosphonatesBisphosphonates More potent than calcitoninMore potent than calcitonin Maxium effect occurs in 2 to 4 daysMaxium effect occurs in 2 to 4 days Trend to use of IV zoledronic acid in Trend to use of IV zoledronic acid in

the acute situationthe acute situation Both are can be renal toxicBoth are can be renal toxic

– More potent than pamidronateMore potent than pamidronate– Administered over a shorter period of Administered over a shorter period of

time (15 minutes vs. 2 hours)time (15 minutes vs. 2 hours)

Prophylactic Prophylactic BisphosphonatesBisphosphonates Pamidronate use in patients with Pamidronate use in patients with

known lytic lesionsknown lytic lesions1717

– Less episodes of hypercalcemiaLess episodes of hypercalcemia– Less pathologic fracturesLess pathologic fractures– Less painLess pain– Less spinal cord compressionLess spinal cord compression– Less need for radiation or surgeryLess need for radiation or surgery

17. Hortobagyi, GN, Theriault, RL, Porter, L, et al for the Protocol 19 17. Hortobagyi, GN, Theriault, RL, Porter, L, et al for the Protocol 19 Aredia Breast Cancer Study Group. Efficacy of pamidronate in reducing Aredia Breast Cancer Study Group. Efficacy of pamidronate in reducing skeletal complications in patients with breast cancer and lytic bone skeletal complications in patients with breast cancer and lytic bone metastases. N Engl J Med 1996; 335:1785. metastases. N Engl J Med 1996; 335:1785.

Newly discovered side Newly discovered side effect…effect… Osteonecrosis of the jawOsteonecrosis of the jaw

Recent case reports of jaw bone Recent case reports of jaw bone necrosis in patients on necrosis in patients on pamidronatepamidronate

EDUCATION neededEDUCATION needed

Fine BalanceFine Balance Chemotherapy can be very toxicChemotherapy can be very toxic

Ratio: benefit vs. toxicityRatio: benefit vs. toxicity Host factors and tumor factorsHost factors and tumor factors

Delicate balance in palliative Delicate balance in palliative situationsituation

Want medications that affect tumor Want medications that affect tumor but do not heavily affect hostbut do not heavily affect host

Fine BalanceFine Balance Chemotherapy can be very toxicChemotherapy can be very toxic

Ratio: benefit vs. toxicityRatio: benefit vs. toxicity Host factors and tumor factorsHost factors and tumor factors

Delicate balance in palliative Delicate balance in palliative situationsituation

Want medications that affect tumor Want medications that affect tumor but do not heavily affect hostbut do not heavily affect host

Psychology of CancerPsychology of Cancer

Psychological evolution during Psychological evolution during cancer treatmentcancer treatment

Many people have fought very Many people have fought very hard with their diseasehard with their disease

Chemotherapy for “relief” not Chemotherapy for “relief” not “cure” can be difficult concept for “cure” can be difficult concept for patientspatients

ART of medicineART of medicine

EvolutionEvolution

Chemotherapeutic protocols that Chemotherapeutic protocols that have less side effectshave less side effects

molecular targeted therapiesmolecular targeted therapies– Attack tumor specifically Attack tumor specifically – Less effect on hostLess effect on host

Breast cancerBreast cancer

Colon CancerColon Cancer

Prostate cancerProstate cancer

Lung cancerLung cancer

Breast CancerBreast Cancer Aromatase inhibitors for ER positive Aromatase inhibitors for ER positive

tumorstumors– Anastrozole, Letrozole, ExemestaneAnastrozole, Letrozole, Exemestane

Trastuzumab (Herceptin)Trastuzumab (Herceptin)– Humanized monoclonal antibody Humanized monoclonal antibody

targeting Her-2/neu protein on breast targeting Her-2/neu protein on breast cancer cellscancer cells

– Inhibits growth factor signal Inhibits growth factor signal transductiontransduction

– Tolerated quite wellTolerated quite well

Colon CancerColon Cancer Capecitabine (Xeloda)Capecitabine (Xeloda)

Oral drug that is transformed into 5-Oral drug that is transformed into 5-FU with three enzymatic reactionsFU with three enzymatic reactions– Final enzyme is at higher levels in tumor Final enzyme is at higher levels in tumor

cellscells– Contributes to drug’s less toxic side Contributes to drug’s less toxic side

effect profileeffect profile Less stomatitis, less myelosupressionLess stomatitis, less myelosupression

Targeted GI TherapiesTargeted GI Therapies BevacizumabBevacizumab

– Monoclonal antibody to Monoclonal antibody to vascular vascular endotheial growth factor receptorendotheial growth factor receptor

– Some cardiac toxicitySome cardiac toxicity

CetuximabCetuximab– Monoclonal antibody to Monoclonal antibody to human human

epidermal growth factor receptorepidermal growth factor receptor– Skin toxicitySkin toxicity

Prostate CancerProstate Cancer LHRH analoguesLHRH analogues

Leuprolide (Lupron)Leuprolide (Lupron)

Goserelin (Zoladex)Goserelin (Zoladex)

Stop testosterone production with Stop testosterone production with limited side effectslimited side effects

Lung CancerLung Cancer

In stage IV disease patients who In stage IV disease patients who receive Cisplatin based doublet receive Cisplatin based doublet chemotherapy live longer and feel chemotherapy live longer and feel better than best supportive carebetter than best supportive care

Hard to balance side effectsHard to balance side effects

Gefitinib (Iressa)Gefitinib (Iressa)

Targets epidermal growth factor Targets epidermal growth factor receptor (tyrosine kinase small receptor (tyrosine kinase small molecule inhibitor)molecule inhibitor)

May have a role in the palliation May have a role in the palliation of advanced non small cell lung of advanced non small cell lung cancer patientscancer patients

Palliative Care DebatePalliative Care Debate Do not accept any patient on Do not accept any patient on

“active” therapy“active” therapy This needs to be further elucidatedThis needs to be further elucidated Patients being palliated with Patients being palliated with

chemotherapy or targeted therapies chemotherapy or targeted therapies still have other palliative care issues still have other palliative care issues and needsand needs

Should a patient still on Xeloda for Should a patient still on Xeloda for breast or colon cancer not be breast or colon cancer not be admitted to St. Boniface 8A?admitted to St. Boniface 8A?

Today…Today…

THE THE CURRENT CURRENT COURSE...COURSE...

Smoking and cancerSmoking and cancer

Respiratory systemRespiratory systemGenitourinary systemGenitourinary system

Bladder, kidney, ureters and renal Bladder, kidney, ureters and renal pelvicpelvic

Gastrointestinal systemGastrointestinal systemEsophagus, pancreasEsophagus, pancreas

Statistical associationStatistical associationStomach, prostate, cervix, penis, Stomach, prostate, cervix, penis,

colonic polyp and acute leukemia.colonic polyp and acute leukemia.

ThanksThanks