Category Archives: Hematology and Oncology

ZSFG Morning Report 6.12.2017 – High Flow Oxygen and PD-1 inhibitors

Thank you to the ICU team and Bennett Caughey for presenting the case of a middle-aged woman with advanced metastatic SCC of the lung, who presented with hypoxia and respiratory distress after esophageal stent placement.

Take Home Points

  • Escalating hi-flow oxygen needs should warrant ICU evaluation.
  • Differential for noninfectious causes of cavitary lung lesions includes neoplasm. SCC is the primary lung malignancy most likely to cavitate.
  • PD-1 inhibitor therapy can cause pneumonitis, but is a diagnosis of exclusion; infection and malignancy should be excluded. Median duration of treatment prior to development of pneumonitis is 2.8 months.


High flow oxygen

  • What is it? Heated and humidified air that allows for comfortable delivery of higher flow oxygen
  • No specific threshold that absolutely warrants ICU level care (institution dependent) but an escalating requirement is worrisome and should prompt ICU evaluation
  • Liters per minute (LPM) and FiO2 are the two variables that can be manipulated, again this is institution dependent
  • High flow oxygen also provides a small amount of positive pressure. Also found to have decreased 90-day mortality in pts with nonhypercapnic acute hypoxemic respiratory failure.

What you need to know about PD-1 inhibitors:

  • PD1 stands for programmed cell death 1, and is involved in check point signaling pathway
  • PD1 inhibitors block normal inhibition response, and therefore boost immune response against cancer cells.
  • Nivolumab and pembrolizumab: currently being used in pts with advanced melanoma and non-small cell lung cancer.
  • The most common immune-related adverse events are typically transient, but can occasionally be severe or fatal. The most commonly implicated organ systems are dermatologic, diarrhea/colitis, hepatotoxicity, and endocrinopathies.
  • Overall incidence of PD-1 inhibitor related pneumonitis is ~5%
  • In general, mild symptoms can be observed and PD-1 therapy can be withheld. In more severe cases, checkpoint inhibitor therapy should be permanently discontinued, and consider use of steroids.

MOFFITT ENDOCRINE REPORT PEARLS 5/17/17: Hypercalcemia of Malignancy and PTHrP!

Hey Everyone! Thanks to Vaibhav for presenting the case of an older woman with newly diagnosed bladder cancer who presented with weight loss and failure to thrive, found to have severe hypercalcemia with workup pending. We suspected she might have PTHrP-mediated hypercalcemia, a known association with urothelial carcinomas. Pearls on PTHrP below!


Top Pearls:

  1. PTHrP is the most common cause of hypercalcemia in non-metastatic solid tumors
  2. PTHrP-related hypercalcemia is typically a finding in advanced disease with poor prognosis
  3. PTHrP acts primarily on bone and kidneys to cause hypercalcemia, not the GI tract


For those who want more info:

Check out Myung’s pearls on hypercalcemia:

*Important general pearls on hypercalcemia of malignancy: 1) It occurs in 10-30% of patients with advanced tumors. 2) It is the most common cause of hypercalcemia in the inpatient setting. 3) Prognosis is poor (up to 50% 30-day mortality).

Now some more specific info on PTHrP!

What is PTHrP?

  • Normal gene product expressed in several tissues
  • Also called humoral hypercalcemia of malignancy (HHM)
  • The most common cause of hypercalcemia in patients with non-metastatic solid tumors
  • Most often in patients with advanced disease and poor prognosis (not usually an early finding)
  • Solid tumor associations: SCC, renal/bladder, breast, ovarian
  • Liquid tumor associations: NHL, CML (blast phase), T-cell leukemia/lymphoma

How is PTHrP related to PTH?

  • First 13 N-terminal amino acids are homologous to PTH (PTH = 84 AAs, PTHrP =139-173 AAs)
  • Binds to same PTH-1 receptor as PTH: bone resorption, renal Ca reabsorption/phos wasting
  • Structural divergence after first 13 amino acids: less likely to stimulate 1,25 vit D production, does not increase intestinal Ca absorption
  • Thus, PTHrP hyperCa is from bone/renal only, while PTH hyperCa is also from GI
  • Lab findings in PTHrP hyperCa: 1) elevated PTHrP, 2) low PTH, 3) normal/low 1,25-vit D

How is measurement of PTHrP useful (aside from diagnosis)?

  • Tumor marker: helps to assess treatment response
  • Prognostic marker: worse survival if PTHrP level > 12 pmol/L, which predicts less robust response of hyperCa to bisphosphonate therapy

HyperCa Malignancy



Have a great day everyone!


MOFFITT HEME/ONC REPORT PEARLS 5/12/17: Warfarin-Related Bleeding!

Hey Everyone! Thanks to Matt for presenting the case of an elderly man with heart failure and valve replacement on warfarin presenting with a fall and found to have severe vital sign abnormalities and INR of 13! Pearls below:


Top Pearls:

  1. 1st steps in warfarin-related bleeding: stabilize and give IV vitamin K.
  2. PCC is generally preferred over FFP where available. Give IV vitamin K too!!


For those who want more info:

Rachel Stern wrote excellent pearls on supratherapeutic INR in patients on warfarin, see below:

Here’s some additional info on warfarin reversal agents:

If no bleeding:

IV agents should only be needed if bleeding is present. Otherwise, you can get by with just holding the warfarin, and giving PO vitamin K if INR is very elevated. In the updated 2012 ACCP guidelines, the threshold for giving PO vitamin K for an elevated INR in the absence of bleeding was changed from >9.0 to >10.0.

If bleeding:

IV vitamin K: Works within 12-24 hours. IV and PO vitamin K reverse INR equally effectively, IV just works faster. **ALWAYS give IV vitamin K ASAP if bleeding on warfarin.**

Dosing: 5-10 mg IV no faster than 1 mg/min to reduce anaphylaxis risk. Can repeat every 12 hours if INR remains elevated.

PCC: Prothrombin complex concentrates, contain clotting factors, protein C/S and low doses of heparin to prevent premature clotting factor activation. Corrects INR faster than FFP and with less volume, often within 10 minutes. Effect is transient (hours) so must administer IV vitamin K simultaneously. 5x more expensive than FFP.

  • Kcentra: 4 factor unactivated (II, VII, IX, X)
  • Bebulin: 3 factor unactivated (II, IX, X)
  • FEIBA: 4 factor activated (II, VII, IX, X) [“factor eight inhibitor activity bypassing agent”] used primarily in hemophilia patients or DOAC reversal, not used routinely in warfarin bleeding.

No great evidence directly comparing 4 vs 3 factor concentrates, but generally 4 factor concentrates are preferred. Can be thrombogenic.

Dosing: Fixed dosing non-inferior to weight-based dosing; give 1500-2000 IU at 100 IU/min.

*Pearl: ACCP 2012 guidelines recommend PCC over FFP for warfarin-associated bleeding.

FFP: Fresh frozen plasma, contains all clotting factors at physiologic concentrations. Takes 30 mins or more to give one unit, so takes several hours to administer whole dose. Must be ABO compatible. Effect is transient (hours) so must administer IV vitamin K simultaneously.

Dosing: Start with 4 units (1L volume), up to 8 units are often required for full reversal.

rFVIIa: Recombinant activated factor 7. Works within 10 minutes. Effect is transient (hours) so must administer IV vitamin K simultaneously. Not typically given as monotherapy because does not replace other factors. Can be thrombogenic.

Dosing: 20 mcg/kg bolus

See summary table below:

Warfarin bleeding



Have a great day everyone!


MOFFITT MORNING REPORT PEARLS 5/5/17: Cavitary Lung Lesions and Castleman Disease!

Hey Everyone! Thanks to Braden for presenting a super interesting case of a middle-aged man with multicentric Castleman disease who was incidentally found to have a cavitary pulmonary nodule! We discussed an extensive differential for cavitary lung nodules and reviewed Castleman disease. Pearls below!


Top Pearls:

  1. The ddx of cavitary lung lesions is broader than just TB/fungal/cancer! See below.
  2. Unicentric Castleman disease is usually curable while multicentric has a variable prognosis.
  3. Steroids predispose to infection with aspergillus, cryptococcus, nocardia, PCP, and legionella.


For those who want more info:

Cavitary lung lesions:

Here’s the differential we discussed with Harry’s help!

  • Infection! TB, NTM, fungal (crypto, dimorphics, molds, rarely PCP), bacterial (staph, strep, nocardia, actinomyces, rhodococcus), strongyloides, rarely viral (CMV, VZV)
  • Malignancy! Primary lung cancer, metastases, lymphoma, rarely Kaposi sarcoma
  • Rheumatologic! Vasculitis (GPA, rarely MPA), sarcoidosis
  • Emboli! Bland or septic


Castleman disease:

Now a review of Castleman disease. Or maybe your first time learning about it. That’s ok too. 🙂

Castleman disease, aka angiofollicular lymph node hyperplasia! Obvi.

Commonly associated with HIV and HHV-8 but not always! Our patient today was negative for both.

Divided into unicentric and multicentric Castleman disease, which have very different prognoses (hint, unicentric is more favorable…).

Unicentric (UCD):

  • Lymphoproliferative disorder of young adults
  • Usually asymptomatic, enlarged lymph node discovered incidentally on exam or imaging
  • Node/mass is most often in mediastinum or lung
  • Biopsy shows polyclonal expansion (ie. NOT a monoclonal disorder!)
  • PET/CT rules out involvement of other sites
  • Complete resection of the involved lymph node is curative with excellent prognosis
  • If resection not possible, systemic therapy as in MCD (see below)

Multicentric (MCD):

  • Lymphoproliferative disorder (usually plasma cells) presenting in 5th or 6th decade of life
  • Peripheral lymphadenopathy and systemic symptoms
  • Biopsy shows polyclonal expansion (ie. NOT a monoclonal disorder!)
  • PET/CT demonstrates involvement of multiple sites
  • Treatment depends on HIV/HHV-8 status and disease aggression
  • HIV/HHV-8 neg without organ failure: anti-IL-6 immunotherapy (siltuximab or tocilizumab)
  • HIV/HHV-8 neg with organ failure: etoposide + rituximab
  • HIV/HHV-8 pos: ARVs + ganciclovir + rituximab, with etoposide if aggressive disease
  • Prognosis is variable, worse with HIV infection in which a rapidly progressive form can lead to death within weeks!

There is a strong association between MCD and POEMS syndrome; 15-50% of patients with POEMS also have MCD. POEMS stands for polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes.

RCT showing efficacy of siltuximab in MCD leading to FDA approval. Side effects included pruritis, weight gain, rash, hyperuricemia, URI, fatigue, night sweats, and anemia. Serious adverse events included pneumonia, anaphylaxis, and sepsis.

*Harry pearl: High dose steroids predispose to five infections in particular- aspergillus, cryptococcus, nocardia, PCP, and legionella!



Have a great day everyone!



Hey Everyone! Crazy oncology report today with Andrew and Josh presenting the case of a middle-aged man with shortness of breath and fevers, found to have endobronchial B-cell lymphoma almost completely obstructing the entire airway! Eek! We watched an awesome video of the interventional pulmonologists freezing and removing the endobronchial masses. Pearls below:


Top Pearls:

  1. DLBCL is the most common non-Hodgkin lymphoma.
  2. Lymphoma causing oncologic emergency (e.g. airway compromise) should be treated promptly with steroids with monitoring and prophylaxis for tumor lysis syndrome.
  3. Hodgkin and many non-Hodgkin lymphomas are curable in the majority of patients. Mantle cell lymphoma portends the worst prognosis of the group.


For those who want more info:

Lymphoma Classification:

Lymphomas can be divided into Hodgkin and non-Hodgkin lymphoma. The most common non-Hodgkin lymphomas are: DLBCL (25%), mantle cell, Burkitt, CLL/SLL, follicular, lymphoplasmacytic, and marginal zone.

Lymphoid neoplasm classification was updated in 2016, including a lot of genetic markers to help with subclassification:


A brief primer on the five major categories of mature lymphoid neoplasms:

Hodgkin lymphoma is its own group including classical and nodular Hodgkin lymphoma.

Mature B-cell neoplasms include CLL, marginal zone lymphoma, hairy cell leukemia, myeloma, MALT lymphoma, follicular lymphoma, mantle cell lymphoma, DLBCL, Burkitt lymphoma, and many others.

Mature T and NK neoplasms include T cell leukemia/lymphoma, mycosis fungoides, Sezary syndrome, cutaneous T cell lymphoma, anaplastic large cell lymphoma, and others.

Post-transplant lymphoproliferative disorder (PTLD) is its own group.

Histiocytic and dendritic cell neoplasms include Langerhans cell histiocytosis, Erdheim-Chester disease, and others.

*Pearl: There is an “unclassifiable” B-cell lymphoma with features intermediate between DLBCL and classical Hodgkin, so not all tumors may fit perfectly into a clear category.



Treatment of Hodgkin lymphoma = ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine)

Treatment of most non-Hodgkin lymphoma = R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone)

What to do overnight for an oncologic emergency due to lymphoma (e.g. airway obstruction)?

  • Steroids!!
  • Check tumor lysis labs and LDH and start prophylaxis.
  • Some chemo (cytoxan and rituximab) may be started as path is pending (call oncology!)
  • Call relevant consultants (ENT for airway, neurosurg for spine, etc).


*Pearl: There are case reports of steroids causing tumor lysis syndrome in high risk patients! Start TLS prophylaxis even if you are just treating with steroids!

*Pearl: All DLBCL is at least intermediate risk for tumor lysis syndrome and should receive allopurinol (in addition to hydration and monitoring). Bulky DLBCL or LDH >2x ULN (and all Burkitt lymphoma) is high risk and merits rasburicase!



There are different prognostic scoring systems for each of the different lymphomas.

As an example, for DLBCL, risk factors for poor prognosis are older age, elevated LDH, poor performance status, advanced stage disease, and number of extra nodal disease sites. But the risk factors may differ slightly for each type of lymphoma.

Hodgkin: 5 year survival 98% for low risk, 67% for high risk.

DLBCL: 5 year survival 90% for low risk, 50% for high risk.

Burkitt: 5 year survival 90% in younger patients, 54% overall.

Follicular: 5 year survival 91% for low risk, 52% for high risk.

Marginal zone: 5 year survival 83% for low risk, 56% for high risk.

Mantle cell: 5 year survival 60% for low risk, 20% for high risk (worst prognosis).




Have a great day everyone!


MOFFITT AM REPORT PEARLS 4/5/17: ITP and Transfusion Reactions!

Hey everyone! Thanks to Kenny for presenting a case of a young man with severe thrombocytopenia diagnosed with ITP who also had an anaphylactic reaction to platelet transfusion! Thankfully he did well. Since we’ve had prior pearls on ITP and anaphylaxis (links at the end), pearls below on transfusion reactions:


Top Pearls:

  1. The most important steps in management of acute transfusion reactions are stopping the transfusion and patient assessment.
  2. If isolated urticaria, it is likely ok to continue the transfusion as long as there are no other symptoms or signs of a more concerning reaction.
  3. Make sure to order a transfusion reaction workup (lab medicine can help you).


For those who want more info:

Approach to acute transfusion reactions:

All of the following steps should be taken immediately in anyone with an acute reaction:

  1. Stop transfusion and save bag/tubing (likely ok to continue if isolated urticaria)
  2. Assess patient vitals, symptoms, exam
  3. Maintain patent IV line with NS
  4. Confirm correct product!
  5. Contact lab medicine to initiate transfusion reaction workup


Specific acute reactions (during transfusion or within 24 hours):



Urticaria (1-3% of transfusions): Reaction to donor serum proteins, most common reaction.

  • Tx: Antihistamines, ok to continue transfusion as long as no other sx.

Febrile non-hemolytic transfusion reaction (FNHTR) (0.1-1% of transfusions): Donor WBC cytokines.

  • Tx: Symptomatic, leukoreduce future products (all products are leukoreduced at UCSF)
  • *Pearl: With platelet transfusion, a similar reaction can occur with chills but without fever.

TACO (volume overload) and TRALI (acute lung injury)



Anaphylaxis (1:20,000-1:50,000): See prior ZSFG pearls below.

  • Tx: Stop transfusion! Epinephrine, fluids, steroids, antihistamines.
  • *Pearl: Patients with IgA deficiency at particularly high risk.

Acute hemolytic transfusion reaction (AHTR): ABO incompatibility (virtually all are RBCs)

  • Tx: Stop transfusion! Fluids, supportive care.

Sepsis/Endotoxic shock:

  • *Pearl: Highest risk product is platelets (1:50,000 compared with 1:5 million pRBCs)
  • *Pearl: Remember to culture patient’s blood and also product bag!
  • Tx: You know this 🙂


Prognosis of acute transfusion reactions: Overall very rare to die of acute transfusion reaction, approx. 1-2 deaths per million acute reactions.

  • Most fatal are TRALI and TACO, followed by acute hemolysis, sepsis, and anaphylaxis.

Delayed transfusion reactions (days to weeks):

  • Delayed hemolysis
  • Thrombocytopenia
  • Transfusion-associated GVHD (almost uniformly fatal!)


Previous Moffitt Blog posts on ITP:

Previous ZSFG Blog post on anaphylaxis, including diagnostic criteria (which Cary recited for us!):



Have a great day everyone!


MOFFITT AM REPORT PEARLS 4/3/17: GI Bleeding and DOAC Reversal!

Hey everyone! Thanks to Chloe for presenting the case of a middle-aged man with metastatic SCC who presented with bleeding from either a GI source or from the tumor itself. Unfortunately, the course was complicated by cardiac arrest. We talked about some great core topics today, pearls below:


Top Pearls:

  1. Evidence supports a transfusion threshold of hgb 7.0 for GI bleeding, but if someone is unstable and actively bleeding, transfuse regardless of hgb level!
  2. Dabigatran has a novel reversal agent, idarucizumab, used in severe bleeding. The Xa inhibitors do not currently have a reversal agent.
  3. Other DOAC reversal strategies include drug removal, antifibrinolytic agents, and PCC.


For those who want more info:

Seems like we’ve talked about ANCA vasculitis and eosinophilia enough recently, so as the great Christina Aguilera advises us, let’s get Back to Basics! (with a bit of DOAC reversal at the end, which is admittedly less basic)

Upper GI bleed:

  • JAMA Rational Clinical Exam series: Does this patient have a severe upper GI bleed? 2012.
  • NG lavage with blood or coffee grounds has a positive LR of 9.6 for UGIB, but sensitivity is only 44%! If it’s there, you’re likely dealing with UGIB, but if it’s not, you still might be!
  • The other features that have good likelihood ratios for UGIB are melena on exam (or history) and BUN/Cr ratio >30.
  • Blood clots in the stool make UGIB much less likely (LR 0.05).
  • The Blatchford prediction score efficiently identifies patients who do NOT need urgent scope. Score components are HR, BP, hgb, BUN, melena, syncope, liver disease, and heart failure.
  • *Pearl: We usually use a transfusion threshold of hgb 7.0, but if someone is unstable and actively bleeding, transfuse regardless of hgb level!


Hyperkalemia treatment:


*Pearls: 1) Bicarb is most helpful if the patient is acidotic in addition to hyperkalemic; if they’re not acidotic, you can hold off. 2) Pay attention to the volume exam before giving diuretics for hyperkalemia! Don’t give if hypovolemic.


H’s and T’s, treatable causes of cardiac arrest:

Hs and Ts

DOAC reversal in setting of major bleeding:

  • DOACs are either thrombin inhibitors (dabigatran) or Xa inhibitors (rivaroxaban, apixaban)
  • Dabigatran has a reversal agent: idarucizumab.
  • The Xa inhibitors do not currently have a reversal agent.
  • Aside from idarucizumab, strategies for reversal for major bleeding include:
    • Drug removal (HD for dabigatran, activated charcoal for all agents if recent ingestion)
    • Antifibrinolytic agents (e.g. tranexamic acid)
    • PCC (activated FEIBA for dabigatran, unactivated Kcentra for Xa inhibitors)
    • Of note, FFP, cryo, and rFVIIa are generally avoided due to lack of data and associated risks, though FFP may be used to correct coexisting coagulopathy
    • RBC and platelet transfusions are used as needed
    • If renal function normal, half-life of dabigatran is 12-17 hrs, and half-life of Xa inhibitors is shorter, 5-15 hrs.



Have a great day everyone!