Yale Internal Medicine

Oncology Rotation

Intern Survival Guide

Created By

Roman Groisberg and Michael Cecchini

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Disclaimer

This recommendations contained herein are meant to be general guidelines and not as a substitute for clinical judgment. If you are not sure of what to do, as your resident. As always, your attend-ing has final say over management decisions.

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Table of Contents Neutropenic Fever 4

Thromboembolics/VTE/Thrombocytopenia 8

Pain Management 10

Cord Compression 12

Tumor Lysis 14

Massive Hemoptysis 16

DIC 18

Pleural Effusion 19

Pericardial Effusion 20

Malignant Ascites 21

Brain Mets and Seizures 22

Diarrhea 24

Emesis 25

Delerium 26

SVC Syndrome 27

Paraneoplastic (SIADH, HyperCa, CBC abnrml) 28

Bowel Obstruction 30

Acute Cholangitis 31

Ureteral Obstruction 32

Neutropenia Prophylaxis 6

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Neutropenic Fever

This is an emergency and the goal is to have cultures and antibiotics started in 1 hour.

Definition

Neutropenia- an ANC of <500 cells/mm or an ANC that is ex-pected to decrease to <500 during the next 48h.

Fever- a single oral temperature measurement of >38.3C (101F) or a temperature of >38C (100.4F) sustained over a one hour period. At YNHH the usual practice is one tempera-ture of 100.4F

Required workup

Chemistry, CBC, LFT, 2 sets of blood cultures as well as cul-tures from each lumen of a central venous catheter, urine cul-tures, and any other sites of suspected infection. A chest x-ray should be obtained (Preferably PA/Lat)

Empiric Therapy

Patients that are high risk and admitted should receive a Beta lactam antibiotic that has anti-pseudomonal activity. The IDSA recommends cefepime, meropenem/imipenem, or pipercillin-tazobactam. At Yale the first choice is pipercillin-tazobactam.

Aztreonam 2 grams IV q8 hours (for patients with penicillin or cephalosporin allergy)—this requires non-formulary pharma-cist approval

Vancomycin is commonly used as part of the initial empiric regimen for febrile neutropenia because most patients are on Gram-negative prophylaxis. It can be D/C’d by day 3 if cul-tures are negative.

Modifications to this regimen should include: early initiation of daptomycin/linezolid if patients have a history of VRE, car-bapenem in those with a history of ESBL, and tigecycline if there is a history of Klebsiella Pneumoniae Carbapenemase.

Empiric antifungal therapy should be considered if fever is per-sistent after 3-4 days of antibiotic therapy.

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Antiviral therapy is only recommended if there is clinical or laboratory evidence of active viral disease, but often given em-pirically at YNHH. Check attending note.

G-CSF and GM-CSF are not currently recommended as part of the regimen when treating febrile neutropenia.

Duration of Therapy

With clinically/microbiologically documented infections the du-ration of therapy is dictated by the organism/site, but should continue at least until the duration of neutropenia has passed (ANC >500).

If fever remains unexplained the initial regimen should con-tinue until the ANC is >500. If an appropriate treatment course has been completed the patient may be switched to an oral flouroquinolone until the ANC is >500.

Localizing Symptom pearls

Sinusitis: get sinus CT, it could be Mucor

Respiratory: Low threshold for non-con CT. BAL with gallacto-manin for aspergillus

Abdomen: Low threshold for abdominal CT, make NPO, place NG tube. Consider teflitis: this needs caspofungin

Other Considerations for neutropenic patients:

All patients are in private rooms; compliance with hand hygiene is critical to preventing infection in this population.

Patients must wear a mask when leaving the room.

Flowers and plants are not allowed in the patient’s room.

Patient is assisted with and educated about mouth care (with normal saline rinses) and perirectal hygiene. Do not order Chlorhexidine/Peridex mouth wash for these patients—there is no evidence to support that this is helpful—we provide patients with saline rinses.

Consider ordering Caphasol to help prevent mucositis as well as provide lubri-cation or Mouth-cote, an artificial saliva. Oral mucosa should be inspected daily. Diet may need to be modified in patients with severe mucositis. Pain meds may also be required and in severe mucosits a PCA should be ordered.

Rectal exams, rectal temperatures, rectal tubes, enemas, and suppositories are contraindicated in neutropenic patients.

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Blood Cultures on NP 11 & NP 12

Patients with tunneled central lines (port/Hickman) re-quire central cultures when:

Patient is newly admitted for fever

It is the first NF since admission

Patient is immunosuppressed, on high dose ster-oids with suspected bacteremia

Patients with PICCs or TLCs should not have these lines cultured unless unable to obtain peripheral.

If the criteria listed applies to the patient, one set should be drawn from each lumen of the CVAD and one set should be drawn peripherally.

If RN is unable to obtain peripheral cultures, the RN will proceed through the algorithm. MD may be asked to draw culture peripherally or arterially or make the decision to draw an additional set centrally. Please document the inability to draw peripherally and the de-cision to draw centrally in your note.

If criteria listed does NOT apply to the patient, two sets of peripheral cultures are drawn.

Exemption criteria include change in mental status, hemodynamic instability, consideration of calling RRT.

Neutropenia Prophylaxis

Fluoroquinolone (PPx for Gram negatives from gut). IDSA rec-ommends cipro, but our formulary has Moxifloxacin 400 qday. Watch for strep viridans.

Acyclovir (400mg BID) for Zoster re-activation.

Diflucan (400mg PO daily) for patients on steroids

Voriconazole (100-200mg BID PO) for deep neutropenia. Look for visual hallucinations as a side effect.

Bactrim (160mg TIW) PCP propylaxis for long term steroids. Alternately use pentamidine monthly.

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VTE

Prophylaxis:

In general all hospitalized cancer patients should receive VTE prophylaxis! Very mobile hematology patients can be excluded.

Contraindication: active major bleeding or recent intracranial bleed (<4 wks)

Propylaxis: Enoxaparin (Lovenox) 40mg daily or Heparin 5,000U subq q8hrs. These drugs are equivalent in prevention and side effect rates.

VTE treatment:

Goal is to prevent recurrence, not treat current DVT Enoxaparin 1mg/kg q12 hours is preferred over Heparin,

Warfarin, or Dabigatran in patients with Cr Cl > 30. Check anti-Xa level if suspect sub therapeutic levels (obesity)

Use Heparin 80u/kg IV bolus, then 18 U/kg/h infusion if Cr Cl < 30. Monitor PTT q6 hours. Goal 50-90. Monitor q24hr when PTT stable.

Treatment with LMWH should continue for at least 6 months (all pts) and maybe longer for those with metastatic disease or active chemo.

Warfarin is an acceptable alternative for long-term treatment in those unable to take Enoxaparin. Goal INR 2.0-3.0

Contraindications: Active major bleeding, uncontrolled ma-lignant hypertension, liver failure with coagulopathy, inherited bleeding disorder, Plt count <20,000, expected invasive proce-dure (LP, surgery, epidural catheter placement).

Presence of intracranial tumor or brain mets is NOT a contra-indication.

Relative Contraindications: high risk intracranial mets (listed below), active GI ulcer, minor bleeding (hematuria), re-cent intracranial bleed (<4 wks), recent surgery or bleeding (< 2 wks), Plt count <50,000.

Thyroid, melanoma, renal cell, and choriocarcinoma brain mets have the highest rate of spontaneous intracranial bleeding. Get a non-contrast head CT to evaluate for recent intracranial bleed (<4 wks).

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Avoid using LMWH initially in these patients. Use Heparin drip without bolus! May transition to LMWH upon discharge.

Vena Cava filter: only if you can’t use anticoagulation or if pt has extension of DVT while anti-coagulated. They have no ef-fect on survival.

DVT recurrence: increase LMWH dose by 25%

Pulmonary Embolism is outside the scope of this guide, please see:

Diagnosis and Management of Life-Threatening Pulmonary Em-bolism. Marshall PS, Matthews KS, Siegel MD.

Thrombocytopenia

Do NOT order any NSAIDs, anticoagulants, or aspirin for a pa-tient with a platelet count <50,000.

Do NOT order anything via the rectal route in patients with thrombocytopenia OR neutropenia. Rectal exams (or any other rectal test) are contraindicated in this population.

Do NOT order urinary catheterization unless absolutely neces-sary.

Do NOT order IM injections unless absolutely necessary .

Ensure that patient has a PPI ordered.

Physical therapy is generally held if platelets are <20,000. If you feel that a patient is safe for PT with a platelet count of <20,000, include this in your

documented plan for the day.

Consider ordering post platelet transfusion counts to determine the effect of the transfusion. This step is

necessary to obtain single donor or HLA-matched

platelets. If the post count is not acceptable, consider

ordering an alloimmunization screen.

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Pain Management Mild Pain: Step I: Tylenol (almost always a good option) or Ibuprofen (usually not a good option as many patients have renal, GI, or platelet derangements). Moderate pain (opiate naïve): Step II: Tramadol (<400mg qD) = Codeine (<360mg qD) + Tylenol (Tyelnol #4) = Hydrocodone + Tylenol (Norco, Vicodin). Tramadol was associated with more SE (dizziness, nausea, constipation) than others. Step II (additional options): Oxycodone (<20mg qD), Morphine (<30mg qD), Hydromorphone (<4mg qD). These drugs are essentially equivalent to other Step II opiates at low doses! Severe pain: step III: Morphine = Oxycodone = Hydromorphone Titration: Morphine reaches tmax in <1hr and has 4 hour duration. Start with morphine 1mg IV q10 minutes and keep giving PRN until patient feels

Drug Name Initial PO dosing PO:IV PO drug: PO morphine

Morphine 15mg 3:1 1:1

Oxycodone 5mg – 3:2

Hydromorphone 1mg 4:1 4:1

Fentanyl – – 100:1

Switching route: Usually converting long acting med to IV when patient is hospitalized and can't take PO. Give 75% of the calculated IV dose to account for first pass me-tabolism. 1. Calculate 24 hour dose and convert to oral morphine 2. Calculate new dose using conversion ratio (eg. 180mg/24hr PO morphine =

60mg IV=10mg q4hr) 3. Dose reduce by 75% **conversion will vary depending on source, so it is important to dose reduce! ***except in thrombocytopenia

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Switching med: This should be done if pain control cannot be achieved because SE prevent uptitration. You should dose reduce by 50% of expected dose to account for incomplete cross tolerance and then titrate up again.

1. Calculate 24 hour dose and convert to oral morphine

2. Calculate new dose using conversion ratio (eg. 180mg/24hr PO mor-

phine=45mg/24hr hydromorphone)

3. Dose reduce 50% (eg. 45mg/24hr x50% = 22mg/24hr = 4mg q4hr)

Transdermal: Fentanyl patch is a preferred method of pain control for patient ease and comfort

1. Calculate 24 hour dose of morphine

2. Calculate fentanyl dose based on 100:1 potency (eg 60mg/24hr morpine =

0.6mg/24hr fentanyl) Side Effects: Nausea related to opioids: treat with metoclopramide (reglan) Constipation: All patients receiving opiates need a bowel regiment! See be-low. CNS: sedation/drowsiness can be treated with methylphenidate or IV caf-feine. Delerium/hallucinations should prompt opiate dose reduction. CKD stage 4 or more: Use fentanyl IV at low doses, start with 50mcg IV q 1hr. Titrate as needed. Then transition to PO

Bowel Regimen: All patients on opioids should be on a stepped BOWEL REGIMEN: 1. → Senna + docusate (Senokot S) 1-2 tabs twice daily or → MOM 30-60 cc twice to three times daily or → Lactulose 30-60 cc twice to three times daily or → Miralax 1-4 T daily

2. Double dose or high dose stimulant + osmotic

3. Methylnatrexone (Relistor) for unresponsive opioid bowel while continuing conventional bowel management preparations (this is normally a short-term intervention).

a. Methylnatrexone is a Mu opioid antagonist that does NOT cross BBB

b. Dosing: 8 mg (81-135lb); 12 mg (> 135 lb) or 0.15 mg/kg sc every other day or as needed not to exceed q24hr

Always treat impaction with enemas/suppositories***

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Malignant Spinal Cord Compression Definition of Malignant Spinal Cord Compression (MSCC): Indentation, dis-placement, or encasement of the Thecal sac that surrounds the spinal cord or Cauda Equina by spinal epidural metastases or by locally advanced cancer. Most commonly seen in Breast, Lung, and Prostate cancer. Also commonly seen in Non-Hodgkin’s Lymphoma, Multiple Myeloma, Renal cancer, Colorectal cancer, and cancer of unknown primary. However, it can be seen in ANY malig-nancy. The most common mechanism of spread is a vertebral body mass that grows posteriorly and impinges on the anterior portion of the thecal sac and com-presses the venous plexus which restricts blood flow. In some cases bony frag-ments may also protrude into the epidural space. A less common mechanism is tumor growth from the paraspinal area into the neural foramen, which can more often be seen in lymphoma. Injury appears to initially be vasogenic edema with a local inflammatory reac-tion with increasing macrophage cells and increased VEGF. Dexamethasone has shown to decrease VEGF expression in animal models. Ultimately ischemic-hypoxic neuronal injury appears to occur.

Clinical Features Most commonly seen in the thoracic spine (60-80%), lumbosacral (15-30%), cer-vical (<10%).

Pain is the most common symptom seen in MSCC and is seen in up to 95% of patients, and generally localized to the spine. It may be worse when ly-ing down due to distension of the epidural venous plexus. PEARL: always think of spinal cord compression when dealing with back pain. Motor deficits are seen in up to 85% of patients with MSCC, and up to 66% are unable to ambulate at the time of diagnosis. Sensory deficits are less common than weakness, but usually 1-5 segments be-low the level of compression. Bowel and bladder dysfunction are late in the disease process and suggest a very poor prognosis. Urinary retention is the most commonly seen bladder re-lated issue. Bladder scan for PVR.

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Diagnosis MRI total spine with IV contrast is the imaging modality of choice when suspecting MSCC. It has a sensitivity of 93% and specificity of 97%, and can distinguish between benign and metastatic vertebral collapse. CT is also an effective means of diagnosing MSCC, but the sensitivity and specificity are not that of MRI. With the increased availability of MRI and CT bone scan, plain film xray, and myelography play little role in the diagnosis of MSCC.

Treatment Corticosteroids are generally the initial treatment to acutely improve edema and decrease local inflammation. Dexamethasone 10mg IV loading dose fol-lowed my 4mg q6h, however there is conflicting evidence on the exact dose to use. Place a Foley. Give them a pain and bowel regimen (see pain manage-ment section) ***You must evacuate their bowel before starting senna. Milk + Molasses en-ema works great (for patients with platelet count >50K and not neutropenic). Radiation Therapy (Radiation Oncology consult!) leads to rapid improve-ment in pain and decreases the likelihood of the progression of neurologic defi-cits and offers improvement in neurologic deficits in select patients. It is gener-ally the first line therapy after corticosteroids. Neurosurgery by laminectomy and/or anterior decompression was the main-stay of treatment prior to advances in radiation therapy. While radiation ther-apy is more commonly used to manage MSCC, neurosurgery should be in-volved in all patients presenting with MSCC and offers a more rapid decompression. Neurosurgery is preferred in patients with intraspinal bony fragments, unstable spine where direct fixation is required or impending sphincteric dysfunction requiring a more rapid decompression. Additionally if the diagnosis of malignancy is new and there is there is no tissue diagnosis a neurosurgical approach is preferred with samples sent to pathology for defini-tive diagnosis.

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Tumor Lysis Syndrome Most common disease related emergency you will see in Hematology-

Oncology. Occurs when tumor cells lyse and release potassium, phosphate, and nu-

cleaic acids which get converted into uric acid. The hypoCa is secondary to hyperPhos.

Definition: hyperuricemia (>8 mg/dl), hyperkalemia (>6 mmol/L), hyper-phosphatemia (>4.5 mg/dl), and hypocalcemia(iCa <1.12). At least 2 must be present within 7 days of initiating chemo.

Cairo-Bishop grading: 25% increase in K, phos, uric acid and 25% decrease Ca.

Clinical syndrome is at least 2 lab abnormalities in association with renal insuffiancy, arrhythmias, seizures, or death from multi-organ failure (cytokine release)

Not possible to develop other problems without nephropathy first, as all 3 products are renal cleared.

Initial insult is precipitation of uric acid and calcium phosphate crystals in renal tubules

Can get tumor lysis with any cancer, so be on the lookout and hydrate your patients well!

Usually occurs 24-48 hours after chemo, but can happen within hours. Risks for TLS are rapidly growing tumors (Leukemia and lymphoma esp

NHL and Burkitt’s, small cell lung cancer) Management Measure potassium, phosphorus, calcium, creatinine, uric acid, and urine

output I/O’s are critical! Convey this to your nurse! If they have 2 or more of above lab abnormalities and have developed AKI:

start IVF, call pharmacy for rasburicase (direct uric acid breakdown), and transfer to ICU.

Rasburicase side effects: constipation, diarrhea, vomiting, headache, fever, mucuositis. Dose: 0.2mg/kg

IVF: Normal Saline 3L per meter squared. (Find BSA in title bar of Epic) If they have 2 or more of above lab abnormalities, but have no sx or evi-

dence of renal dysfunction: start IVF, get rasburicase, and check labs q8hrs. Transfer to telemetry floor (none on onc floor)

If they have 1 or less of above lab abnormalities and they have risks for TLS (see above), start IVF and allopurinol 200mg PO qid. Get labs q6-12 hours.

Hyperkalemia is the most dangerous component of TLS and should be managed aggressively.

Call renal immediately for potential urgent dialysis if urine output drops below 50cc/hr. Goal UOP is 2ml/kg/hour. (150 cc/hr in average male)

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Lasix is safe and effective in TLS to reach goal UOP, when patient is being well hydrated! 40mg IV for Lasix naïve patients, or up to 200mg IV for tol-erant pts.

Prevention: Allopurinol 300mg daily (start 48 hours before chemo, ideally)

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Massive Hemoptysis Massive hemoptysis is a medical emergency, appropriate manage-

ment and alerting the required services must be done PROMPTLY. No agreed upon volume to define “massive” hemoptysis, between 100

ml/24h – 1000 ml/24h. Is this carotid blowout? Etiology

Neoplastic (Bronchogenic carcinoma, endobronchial tumors, pulmonary metastases, sarcoma). Hemoptysis is estimated to occur in 20% of patients with lung cancer at some point in the disease process with massive hemoptysis estimated to occur approximately 3% of the time.

Vascular (PA aneurysm, bronchial artery aneurysm, pulmonary infarct, airway-vascular fistula).

Pulmonary (Bronchiectasis, chronic bronchitis, alveolar hemorrhage) Infectious (mycobacteria, fungal, necrotizing PNA and lung abscess). Other causes include vasculitis, trauma, hematological, drugs and toxins. Diagnosis

ABC’s- Airway, Breathing, and Circulation must be assessed immediately. Chest X-ray- a STAT chest x-ray can identify the side of bleeding in 33-

82% of cases and identify the underlying cause in 35%. Computed Tomography– Non-contrast CT is superior to chest radiography

and can localize bleeding in 70-88.5% of cases, and is more efficient than bronchoscopy for identifying the cause of bleeding, which can prevent the need for bronchial artery embolization or fiber-optic bronchoscopy depend-ing on the cause. For CT patients must be stable to travel to the scanner, and it is diagnostic but offers no therapeutic intervention.

Fiber-Optic Bronchoscopy- identifies the site of bleeding in 73-93% of epi-sodes of massive hemoptysis. Rigid bronchoscopy should be the modality of choice to maintain airway patency, ventilation, and improved airway clearance.

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Management

Initial Approach- ABC’s must be evaluated. Massive hemoptysis can lead to airway obstruction. Patients with ongoing hemoptysis not protecting their airway will need to be intubated immediately and anesthesia should be called. Patient also may require volume resuscitation. The patient should be placed in a lateral decubitus position with the bleeding side down to prevent aspiration into the unaffected lung. Urgent rigid bronchoscopy may be re-quired for clearing the airways of blood. Unilateral intubation to the unaf-fected lung can be used under some circumstances.

Anesthesia and Pulmonary must be urgently contacted. Consider calling a TART code (threatened airway response team) The MICU admitting physician should be contacted along with IR (370-

0915). Bronchoscopic Treatment- Emergent rigid bronchoscopy with intubation

should be pursued in patients with respiratory failure. Bronchoscopy allows cold-saline lavage, the addition of topical vasoconstrictive agents, balloon tamponade, endobronchial stent tamponade, silicone spigot placement, laser photocoagulation, and electrocautery.

Bronchial Artery Embolization- allows direct coagulation of the bleeding vessel and should be pursued in patients that have undergone failed bron-choscopic treatment or when the bleeding is not able to be localized but the patient is otherwise stable. Immediate control of hemoptysis is reported in 57-100%, although it is estimated to be much closer to 100%.

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DIC

Diagnosis: DIC never occurs in isolation! Look for underlying cause Look for Sepsis, Malignancy, or Liver diseases as the underlying cause Remember that DIC is a rapidly changing clinical picture, so watch your patients carefully. Most commonly found lab abnormalities are:

Downtrending platelet count is a very sensitive (98%), but not at all specific.

D-dimer elevation (again, not at all specific) PT and aPTT prolongation (present in only 50-60% of cases) Downtrending fibrinogen (not sensitive at all, but levels <200mg/dl

are present in very severe DIC) Scoring system for DIC:

Does the patient have one of the above mentioned causes of DIC? If NO, stop!

Platelet count (<100k = 1,<50k = 2) Elevated D-dimer (moderate increase = 2, strong increase = 3) Prolonged PT ( >3 sec = 1, >6 sec = 2) Fibrinogen level (<100 mg/dl = 1) Calculate score: >=5 compatible with overt DIC: repeat score at

least daily Use this score for prognosis: each “point” increases odds of mortality by 1.29 DIC or Liver Disease? Check Factor VIII: Low in DIC and High in acute liver necrosis! Pearl: ask pre-menopausal women about menses, consider starting them on oral contraceptive. Treatment: Most important is treatment of underlying disease! Platelet transfusion only for counts <50k if bleeding and <10k otherwise. Give one pool (5u) Low fibrinogen can be corrected with 4u of FFP or 2 pools of cryoper-cipitate (10u). This should only be done for actively bleeding patients with prolonged PT and aPTT or fibrinogen <100 mg/dl! FFP is first line. Cryo second line. Cryo works faster in emergency. If your patient is in DIC and is NOT bleeding, use heparin DVT prophy-laxis. Even with platelet counts <50k as these patients are at HIGH risk for thrombi. If patient is having uncontrolled bleeding., give aminocaproic acid (amikar). It can be given IV or PO and inhibits lysis of fibrin. In general, DIC is a harbinger of VERY bad things. Patients are as

likely to hemorrhage as they are to clot. It is important to notify your senior

resident or attending if the above mentioned scoring system is suggestive. It is

equally important to notify the patient and family of these findings as goals of

care discussions should not be delayed!

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Malignant Pleural effusion

Presentation/Diagnosis

Any intrathoracic or extrathoracic malignancy can cause this. Medial survival associated with malignant effusion is 4 months 50% of malignancy related effusions are benign, so stick a needle in it! Tumor blocks lymphatic drainage causing fluid buildup Don’t forget about PE as a cause of effusion in cancer patients! REMEMBER 3-10% of malignant effusions are transudative! ORDER: Pleural fluid (LDH and protein), serum (LDH and protein),

cell count, cytology (non-gyn cases order in EPIC). Cytology only has ~65% diagnostic yield for malignant effusion, so don’t

falsely overinterpret the results. If you suspect malignancy, keep looking! CT is a great adjuvant way of evaluating pleural effusion first Measuring pleural amylase, pH, glucose, cholesterol, or protein adds little

diagnostic utility.

Management

Management of malignant effusions is purely palliative and interventions should be reserved for those that have symptoms only!

Removing large volumes will cause rapid lung expansion and cause alveolar capillary injury resulting in pulmonary edema. This can be avoided by stop-ping thoracentisis when patients describe non-specific chest discomfort

Almost all effusions will re-accumulate within 30 days so don’t re-tap them unless they have life-expectancy <3 months or won’t tolerate pleuradesis.

Pleurodesis is appropriate for patients who have symptoms from the effu-sions and dyspnea that isn’t attributed to other causes as well as a reason-able chance of expanding the lung to contact the pleural and parietal vis-cera.

Consider a pleurex catheter for patients that won’t undergo pleurodesis and are repeatedly symptomatic from their effusion.

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Malignant Pericardial Effusion

Malignant invasion of the heart or pericardium is estimated to occur in 10% of cancer patients and seen most commonly in tumors of the lung, breast, melanoma, and hematologic malignancy. It is a very poor prog-nostic indicator for patients. It is estimated that up to 1/3 of patients that develop tamponade secondary to malignancy will die as a consequence.

Diagnosis Beck’s Triad: 1) Distant heart sounds 2) Hypotension 3) JVD. Re-

member Cardiac Tamponade is a medical emergency! Pulsus Paradoxus- decrease in systolic blood pressure during inspiration

of > 10mmHg. Also note that this can be seen in obstructive lung disease. Expect to see an increase in HR secondary to decreased cardiac output.

Echocardiogram will definitively diagnose a pericardial effusion and hemodynamically significant tamponade and should not be delayed. Call the cardiology fellow overnight if you suspect this!

Fluid samples should be sent for specific gravity, protein content, glucose, urea, LDH, and bacterial cultures. Fluid should always be sent for cytol-ogy to evaluate for malignant cells. Studies for cardiotropic viruses should also be considered.

Epicardial and pericardial biopsies may also be helpful in determining if an effusion is malignant in nature.

Other common causes of pericardial effusion would be viral induced, autoimmune, and radiation induced pericardial infusion.

Treatment Emergent pericardiocentesis is the treatment for a hemodynami-

cally significant tamponade in an unstable patient. When time per-mits this may be done down in the cardiac catheterization lab. However, malignant pericardial effusions have a very high rate of recurrence and often require additional treatment, they are often bloody on pericardio-centesis.

Due to the rate of recurrence the definitive treatment in addition to drainage generally involves one or more of the following: pericardial scle-rosing treatment, creation of a pleuropericardial window, systemic che-motherapy, radiotherapy, and intrapericardial instillation of cytostatic agents.

Intrapericardial treatment of malignancy induced pericarditis with cis-platin has shown a significant decrease in the recurrence of malignant cardiac tamponade at 6 months. Patients with lung cancer as compared to breast and other cancers seem to have a lower rate of recurrence with intrapericardial therapy.

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Malignant Ascites Malignant ascites is a direct result of malignant cells within the peritoneum and confers a very poor prognosis, which is on average 20 weeks. Treatment must take into account life expectancy, and is mainly focused on palliation. In 52-54% of peritoneal carcinomatosis, ascites is the first sign of intra-abdominal malignancy,.

Pathophysiology

Malignant ascites suggests peritoneal carcinomatosis (malignant cells in the peritoneal cavity). The most common tumors that cause carcinomatosis include ovarian, colorectal, pancreatic, uterine, lymphoma, lung, and breast.

Combination of altered vascular permeability and obstructed lymphatic drainage. VEGF is found to be at high levels in malignant ascites and thought to play a role in vascular permeability.

Diagnosis

Unfortunately it is not possible to distinguish benign and malignant ascites by physical exam and imaging and some invasive tests must be pursued.

Abdominal paracentesis is the key test used to make the diagnosis of malignant ascites. In malignant ascites a low serum-ascites albumin gradient and high protein is typically seen. Fluid should be sent for cytology and is estimated to be between 50-97% sensitive. (cytology non-gyn order in EPIC).

Management

Edema, depressed serum albumin, liver metastases are independent poor prognostic factors in malignant ascites.

Traditional therapy includes sodium restriction, diuretic therapy, serial paracentesis, and peritoneovenous shunting.

Large volume paracentesis is the most common method of managing malig-nant ascites, unfortunately fluid often reaccumulates within 72 hours, and patients require serial paracentesis.

Peritovenous shunts return ascites fluid to the venous system by a one way pressure valve with the goal to reduce the need for repeat paracentesis. At Yale a Denver Catheter is more frequently used to prevent the need for re-peat paracentesis. A Denver Catheter allows for the intermittent percuta-neous drainage of ascites and can be done at home.

Diuretics are only estimated to be effective in 43-44% of patients, the most often used diuretic is spironolactone, diuretics are likely most effective in patients with large hepatic metastases.

Abdominal tumor debulking and intraperitoneal chemotherapy has shown to be an effective means of preventing recurrent ascites, and also shows some survival benefit.

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Brain Metastases

Hematagenous spread, so most mets will be in supratentorial distribution

proportional to blood flow. Most prominent at grey-white junction and water-shed areas. Terminal arterioles act as a trap for tumor emboli

Altered sensorium and headache (sometimes mild) are most common presenting symptom: look for multiple lesions or pos-

terior fossa lesion

Other common presentations are weakness and lateralizing sx

(hemiparesis, aphasia, visual fields)

Seizures are a relatively common presentation (10% overall) and very

common in melanoma!

Severe headache, coma, or stroke-like sx should prompt you to think

of hemorrhage into a met. Especially in melanoma, renal cell, or thyroid Ca. Imaging/Diagnosis:

Don't hesitate! MRI with contrast is the best diagnostic test. Beware of renal

dysfunction (contraindication to gadolinium)

Non-contrast CT scan is an acceptable alternative in pt that can't get gadolin-

ium or too unstable for MRI.

Always include infection in your differential as many cancer pts are immuno-

suppressed. LP is not useful in dx of brain mets. Only do if you suspect infx or leptomen-ingeal spread. Treatment:

Dexamethasone is preferred steroid because of low mineral-corticoid effect.

Reduces peritumor edema and causes rapid decompression and decrease in ICP. It is lipophilic and crosses the blood/brain barrier.

Dexamethasone effect onset in 6 hours, peak effect in 3 days

Don't forget to include sliding scale insulin as hyperglycemia expected with

dexamethasone

Psychotic reactions are also relatively frequent (5%) with dexamethasone

Load with dexamethasone 10mg IV followed by 6mg every 6 hours (oral or IV equivalent)

May need to do therapeutic LP for patients with symptoms unrespon-

sive to steroids.

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Consults: Call neurosurgery if a single brain met is detected as this may be amenable to

resection

Call radiation oncology for single or especially multiple mets. Stereotactic

(gammaknife) is preferred as it has less side effects over whole brain radiation.

Seizures

Seiuzure Control Choose a non-P450 inducing anti-epileptic: valproic acid, gabapentin, topi-

ramate, levetiracetam, and lamotrigine.

Keppra (levetiracetam) is on the Yale formulary and has been studied for

this indication.

For status epilepticus in brain mets use Keppra 1500mg IV load with addi-

tional 1500mg in 12 hours. Add Ativan 1mg for refractory status and call neu-rology!

For seizure prevention start Keppra at 500mg PO BID (100% bioavailable)

Traditional chemotherapy is of limited use in CNS mets as most don't cross

BBB.

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Diarrhea in Oncology

Many chemotherapeutic agents have diarrhea as a side-effect Some notorious offenders are 5-FU, Irinotecan, and leuko-vorin. Watch for them in your GI malignancy patients as FOLFOX, FOLFIRI, and FOLFIRINOX all contain these agents. Consider postural vital signs

Start IV hydration with normal saline. Keep an eye on elec-trolytes and divalents. Check and replete daily. Keep track of daily weights.

Check for C.diff and norovirus If your patient develops diarrhea while being treated with

these agents, don’t mess around. Loperamide is the drug of choice. Start with a 4mg dose and proceed with another 2mg every 2 hours or every loose stool until they haven’t had a bowel movement in 12 hours. Then stop loperamide.

If you haven’t made progress with loperamide for 24 hours or your patient is neutropenic or has a fever, add Ciprofloxacin 500mg PO q12 hours x 7 days.

If your patient is still having diarrhea after 48 hours of above regimen, add octreotide 125 microgram TID subcutaneous. It blocks secretion of VIP and prolongs transit time.

Skin care!

RED FLAGS: Cramping, Nausea/Vomiting, Fever, Sepsis, Neutropenia, He-

matochezia, Dehydration, More than 7 bowel movements per day, Hemodynamic instability.

If your patient is having any Red Flag symptoms initiate Oc-treotide at 500 microgram TID subcutaneous. Add ciproflox-acin 400mg IV q12 or 500mg PO q12 if able to take PO. Con-tinue until patient is diarrhea free for 24 hours.

Stool workup: fecal blood, fecal leukocytes, c. diff toxin with reflex pcr, salmonella, E. coli, campylobacter. CBC: extreme leukocytosis should make you think of C. diff, g-csf, or both!

Remember to always think of C. diff as it is the most com-mon nosocomial source of diarrhea.

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Emesis

Common chemo at high risk for emesis: *platin, cyclophos-phamide, dacarbazine, irinotecan, *rubicin, cytarabine.

General practice at YNHH is to start with ondansetron (Zofran) 8mg IV/PO BID as first line. This may be appropriate for moderate nausea, but unlikely to give full relief. Watch the QTc!

Add dexamethasone 8mg PO/IV BID x 2-4 days. May give 20mg burst x1 for very severe symptoms.

Add aprepitant (Emend) 80mg PO daily x2 days. Reduce dexa-methasone dose to 80mg PO daily.

Palonosetron (aloxi) 0.25mg IV x1 is a much more effective 5-HT3 antagonist than zofran (longer half-life and higher affin-ity binding to 5-HT3 receptor). Usually given before chemo-therapy. NOTE: you should not use Zofran for 72 hours d/t Qtc prolongation concerns.

Avoid using metoclopramide (reglan), prochlorperazine (Compazine) or dronabinol (marinol) as these have low thera-peutic index in chemo-induced emesis and are unlikely to be effective without a substantial risk of side effects.

Lorazepam (Ativan) may be added for modest antiemetic effect especially in treating anticipatory emesis.

Costs: Ondansetron is ~ $1 per dose. Polanosetron is ~ $188 per dose. Aprepitant is ~ $100

Emphasis on diet: eating frequent small meals all day, keep-ing some food in your stomach is very helpful. Mainly bland diet, white breads, pasta, potatoes.

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Delirium in Cancer Patients

Most common neuropsych complication of cancer

Up to 85% of terminal hospitalized patients will get delirium. Caused by either direct CNS effect (brain mets) or indirect (meds, electro-

lytes, dehydration, organ failure, infection, vascular complications, or paraneoplasms)

Meds: chemo, opiods, antiemetics, steroids, and benzos are big offenders.

Usually presents the same, regardless of cause!

Presentation: inattention, disoriented, rapid onset, cognitive distur-bance (often swearing), sleep-wake reversal,, delusions, disorganized thought, incoherent speech.

Workup Always inquire about alcohol use! Review med list (pay special attention to above listed meds)

Review labs: notably hyperCalcemia, ?DIC, low Cr clearance.

Could the patient have an underlying infection you missed? Dehydration?

Review vitals, notably pulse ox for hypoxemia Did you miss brain mets or leptomeningeal disease? CT and LP are indi-

cated. Treatment Correct all modifiable factors (based on your workup)

Haloperidol is the drug of choice: 1 to 2mg PO q 4hrs prn. Use 0.5mg PO q4 hrs in elderly.

Unlikely to have extrapyramidal effects at haloperidol doses <3.5mg/d Get a baseline EKG, avoid use if QTc >500

For agitation, can give IV Haldol 5mg or add lorazepam 0.5 to 1mg q4 hrs in conjunction with Haldol.

Zyprexa 2.5 to 5mg PO q12 can be used for long QTc. Comes in dissolv-able wafer. Less likely to work in old people!

Seroquel 25mg q12 PO can be used at night for elderly patients, if seda-tion needed to reverse sleep-wake cycle.

Make sure to put them on CIWA if alcohol is a factor.

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SVC Syndrome

Malignancy (NSC Lung Cancer, SC lung cancer, Non-Hodgkin Lymphoma) = 95% of cases. Thrombosis secondary to catheters.

Average survival for patients with SVC syndrome is 6 months.

Look for: SOB, high PCO2, enlarged neck and red face, JVD, lip cyanosis,

arm/hand swelling (esp on right), venous collaterals visible on chest, stridor, tracheal deviation.

Normal upper body venous pressure is 2-8mmHg, but increases to 20-40mmHg with SVC occlusion. This increased hydrostatic pressure is the cause of your patient’s symptoms.

DO A GOOD NEURO EXAM! Even subtle neuro exam findings should be taken seriously as this could indicate cerebral edema! (Look for: Blurry vi-sion, dizziness, HA, confusion)

Assess respiratory status! Is intubation in their future? Hoarseness,

cough, stridor, dysphagia indicate edema of the larynx. In general, SVC syndrome is rarely fatal. Except in cases of cardio-

pulmonary collapse and cerebral edema. Order a Chest Xray as a good starting point to confirm dx. This will usu-

ally show you the mass. Then proceed to Contrast CT or MRI. These will be necessary for staging anyway.

Staging: 1. Mild: Head/Neck edema, cyanosis, plethora 2. Moderate: mild dysphagia, cough, head/neck/jaw/eyelid immobility 3. Severe: Mild/Mod cerebral/laryngeal edema (headache, dizziness),

Syncope after bending over. 4. Life-threatening: confusion/obtunded, stridor, syncope, hypotension,

AKI

Management

If catheter related thrombus is the suspected cause, remove it and initiate heparin drip (PE protocol in epic order set)

Consult IR/cards for potential EKOS catheter thrombolysis. Stage 1-3, you have time. Call IR/Surgery for a biopsy, Rad-Onc for poten-

tial mass radiation, MedOnc for potential chemotherapy. Your job is now to coordinate care between consultants and make sure they are all talking to each other. Ideally, mass should be biopsied before radiation to make a tis-sue diagnosis.

IR may be able to stent the SVC open, which would provide enormous pal-liative relief.

Stage 4 symptoms: make sure their head is elevated, put them on oxygen, give them a dose of Lasix 40mg IV (reduce hydrostatic pressure), intubate if airway compression is a component.

TELL YOUR NURSE: don’t put IVs in arms, drugs may not absorb properly.

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Paraneoplastic Syndromes SIADH Small cell lung cancer produces ADH and atrial natriuretic peptide

causing Hyponatremia. Pts are always euvolemic on exam. Look for other causes if pt is dry or

overloaded. Look for normal orthostatics, no edema, no JVD, uric acid <4 mg/dl,

BUN < 10 mg/dl, Urine Na+ >40mmol/L, Urine Osm >100 mOsm/kg Pts with AMS or seizures likely developed hyponatremia within 48

hours. Raise Na+ by 1-2 mmol/L per hour. Stop after 8-10 mmol/L in first 24 hours!!! Use MDCALC to figure out your rate of normal sa-line infusion. Don’t wing this!

Remember: NS has 308 mOsm/kg so if pt’s urine Osm are > 308, then NS will further exacerbate hyponatremia. Supplement with salt tabs or consider central line and hypertonic saline administration.

Pts presenting without sx or who have documented chronic hyponatre-mia should be corrected at a rate of 0.5-1.0 mmol/L per hour.

Fluid restrict patients to 1L/d. Hypercalcemia Occurs in up to 10% of cancer patients and portends 50% mortality at 30

days. So don't forget you code discussion! Put your patient on FALL Precautions!

80% caused by PTHrP secreted by squamous cell tumors. Causes bone resorption, renal Ca absorption, and phosphate excretion (thrashing!)

Other 20% caused by direct osteolytic effect of bone mets. Think of this in breast Ca, myeloma, and lymphoma.

Nausea/vomiting, lethargy, and renal failure arise when Ca >14mg/dl

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Hypercalcemia Cont. Workup should include ionized Ca (high), PTH (low-normal), and albumin

(binds Ca). PTHrP test is notoriously unreliable. Discontinue Ca/Vit D supplements and thiazides. Start Normal saline infusion, 125cc/hr is a good starting rate. Add lasix only when you are sure pt has been well hydrated! Dehydration

will worsen the hypercalcemia! Zoledronate 4mg IV x1 or Pamidronate 90mg IV x1 are approved bisphos-

phonates for this indication. Ca levels will decline in 2-4 days and nadir in 4-7 days. Good for 3 wks. Not to be used if CrCl<30

Calcitonin 4 units/kg subQ q12 hrs can be used if CrCl<30. Effect only lasts 2-4 days.

Dialysis is also effective at removing Ca, but arguably inappropriate in this scenario!

CBC abnormalities

Eosinophilia: Lymphoma/Leukemia, Lung, GI, GU. Caused by tumor IL-3, IL-5 secretion. Usually asymptomatic, but can cause wheezing. Treat with steroids.

Leukocytosis: Seen in 15% of solid tumors. Always work up other causes! No need to treat.

Pure red cell aplasia: Seen in Thymoma, Leukemia/Lymphoma, MDS. Hct<20 with low retic count. Normal WBC and Plt. Also check for HIV, Herpes, Parvo, Hepatitis! Treated with immunosuppresants. Don’t use dar-bopoietin!

Thrombocytosis: Plt >400. Caused by tumor IL-6 secretion. Check IL-6 level (paraneoplastic), Jak2 (essential thrombocythemia). No need to treat para-neoplastic thrombocytosis.

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Malignant Bowel Obstruction

Etiology

Internal or external compression for metastatic disease. Other common

causes are adhesions related to previous surgeries or malignancy as well as scarring secondary to radiation therapy.

Most common associated malignancies are colon cancer (28%) and ovarian cancer (42%).

Diagnosis

Presentation: abdominal pain, nausea, vomiting and decreased

flatus or bowel movements.

Nonspecific lab values are seen, including leukocytosis.

Abdominal xrays are a useful first imaging study and may show

dilated loops of bowel, however it can be difficult to differentiated ileus from obstruction.

Abdominal CT with PO contrast is very sensitive for the diagnosis of ob-struction, but the abilitiy to diagnose small peritoneal metastasis as the source can be limited. CT can also differentiate a complete from a partial bowel obstruction.

Treatment

The prognosis of the patient should weigh heavily when deciding on treat-

ment. Malignant bowel obstruction has a median overall survival of 4.7 months, and those that undergo surgery have a 5.0 month overall sur-vival.

Medical Management-

Nausea control (pg 25), NG tube, IVF

The goal: symptom control, while awaiting spontaneous resolu-

tion. successful in up to 45% of patient with partial obstruction and may take between 8 and 11 days.

Medical management in complete obstruction with malignant ob-

struction is only estimated to be successful in 3.8% of cases.

Surgical Management- if conservative management of partial obstruction

fails surgery is successful in 68% of patients. Due to the poor success rates of medical management with complete obstruction surgical management is preferred with 76% of cases showing resolution after surgery. Factors associated with a poor surgical success rate include age > 65 with nutri-tional depletion, rapidly recurring ascites, palpable abdominal mass, dis-tant metastases and poor ECOG status.

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Acute Cholangitis Acute cholangitis is a medical emergency! It requires prompt medical ther-

apy and alerting the appropriate consult services. Acute cholangitis is a bacterial infection of the biliary tree caused by ob-

struction, which most commonly results in fever, jaundice, and abdomi-nal pain.

Diagnosis

Charcot’s Triad – right upper quadrant pain, fever, and jaundice. (Reynold’s pentad includes septic shock and confusion).

Blood Tests- Elevated WBC, LFT abnormalities. Imaging- Abdominal ultrasonography is the most widely available to

study to detect dilation of the biliary tree (and most commonly used at Yale), although it’s sensitivity is low when compared to CT, MRCP, ERCP, and EUS.

Tokyo guidelines for the diagnosis of Acute Cholangitis: two of three of charcot triad plus an elevated WBC, LFT abnormalities, and imaging evi-dence of biliary obstruction.

Causes

The most common causes of obstruction are gallstones, benign stenosis, and malignancy. On the oncology service malignancy is the most common cause and can be frequently seen with malignancy of the biliary tract in-cluding the pancreas. Previously placed biliary stents may also malfunc-tion, which can result in obstruction and patients will present with acute cholangitis.

Obstruction leads to stasis, bacterial colonization, and translocation. The most commonly cultured organisms are e. coli, klebsiella, enterobacter, and enterococcus. Less commonly seen is pseudomonas.

Management

Antibiotics- Prompt IV antibiotic therapy can be lifesaving in acute cholangitis, and while culture data (both past and present) should help guide therapy Pipercillin-tazobactam (Zosyn) at 3.375g q6h is appropriate empiric therapy for patients on the oncology service.

IV Hydration – Patients require aggressive IV hydration to prevent hy-potension and should be bolused with at least 1L IVF and placed on main-tenance fluids at 100-125cc/hr pending other comorbidities such as CHF. In patient where the blood pressure cannot be maintained with IVF urgent transfer to the MICU should be made as these patients can decompensate very quickly.

Prompt consult of the ERCP fellow or on call GI physician should be ob-tained as the patient will ultimately need biliary drainage by ERCP. Some patients are not candidates for ERCP or ERCP is unsuccessful. These pa-tients will require percutaneous drainage by IR and an IR consult should

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Malignant Ureteral Obstruction Ureteral obstruction from malignancy usually suggests a very poor prog-

nosis with median survival estimated at 120-140 days.

Etiology

Rectal, gynecological, bladder, and prostate cancer are the most common malignancies to cause ureteral obstruction.

Metastatic disease from breast, pancreatic and gastric cancers are also common causes of obstruction.

Lymphoceles and side affects from intradbdominal and pelvic radiation are also causes of ureteral obstruction in patients with underlying malig-nancy.

Diagnosis

Patients will likely present with a combination of pain, hematuria, ele-vated serum creatinine, and decreased urine output.

Imaging is required to make the diagnosis; a retroperitoneal ultrasound is first line as it is non-invasive and without radiation. In malignant obstruction a CT will also likely be needed to evaluate the location and anatomy, which is needed for treatment.

Prognosis

Risk stratification models predict 6-month survival and break patients into favorable (69%), intermediate (24%) and poor (2%).

Risk factors include 1) Low serum albumin or Na+ 2) Degree of hy-dronephrosis 3) Three or more events related to malignant dissemination (lung/liver/bone/RP mets, pleural effusion, and ascites).

0 risk factors is favorable risk, 1 risk factor intermediate, and 2-3 poor.

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Management

Prognosis is an important consideration when management, survival is improved but studies have not shown a benefit in quality of life (QoL).

Nephrostomy Tubes- placed in the interventional radiology suite under lo-cal anesthesia. 100% success rates are reported, but a decrease in QoL is noted. Anticoagulants and bleeding disorders are contraindications. Up to 39% of patients will have complications such as pain, blockage, sepsis, and require readmission.

Ureteral Stents- retrograde stenting requires anesthesia, but anticoagula-tion and bleeding disorders are not contraindications. Stents generally are more convenient for patients resulting in a better QoL initially. However stent failure is estimated to be 58%. Attempts at parallel stenting and me-tallic stents seem to reduce compression from malignancy, but are associ-ated with higher UTI and epithelial cell obstruction.

Ureteric Diversion- these options should be the last line after more conser-vative measures have been exhausted. 1) Nephro-vesical subcutaneous stent 2) Cutaneous ureterostomy 3) Transuretero-ureterostomy 4) Urinary Diversion (ileal conduit).

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