Noon Conference: Lung Cancer with Dr. Bazhenova

To kick off our PCCM Friday School block, Dr. Bazhenova, a lung cancer medical oncologist and the UCSD hem/onc program director, joined us for noon report to discuss Lung Cancer. She did a great review of everything from lung cancer incidence to work-up and treatment. Highlights below!

Risk Factors: Tobacco smoke, asbestos, radon, arsenic, polycyclic aromatic hydrocarbons, and ionizing radiation. Of note, 20% of lung cancers are in non-smokers.

Epidemiology: Peak ages 50-69 y/o. 2% before age of 40.

A large percentage of patients present with metastatic disease, because pain receptors do not exist in lung parenchyma, and we can’t directly visualize or palpate the lung!

Incidence by Histology:

  • Non-small cell lung cancer – 80%
    • Adenocarcinoma 40%
    • Squamous cell carcinoma – 30%
    • Large cell carcinoma – 10%
  • Small cell lung cancer – 20%

Clinical Presentation: 70% of patients have symptoms at presentation including cough, hemoptysis, pain, weakness, SOB, weight loss, hoarseness, headache, nausea, and vomiting.

Diagnostic Evaluation: Two things we need to determine are the stage and histology.

  • Imaging: CT scan of chest and abdomen and pelvis, PET scan or bone scan, PFT’s if patient is less than stage IV, MRI brain in SCLC even if symptomatic
  • Biopsy: Make sure to review the imaging yourself to help you determine the best route for biopsy. Options include an EBUS by interventional pulmonology, a transthoracic biopsy by IR, and a bone biopsy (less preferred).

Treatment of Non-Small Cell Lung Cancer: Depends on stage of disease.

  • I-II: Surgery, if possible, followed by adjuvant chemotherapy.
    • If surgery is not an option, XRT
    • In Stage I, there is no need for chemo/XRT after surgery!
  • IIIA: Surgery is not usually considered upfront – use combination of chemotherapy and radiation alone
    • Most controversial stage
  • IIIB: Surgery is not an option – treat with chemotherapy/XRT
  • IV: Systemic chemotherapy – radiation reserved for local control
    • Stage IV diagnosis is not in itself an indication for hospice
    • Evaluate for an oncogenic driver and PD-L1 expression

Management of stage IV non-small cell lung cancer depends on the presence of an oncogenic driver and PD-L1 expression.

You can download the slide deck here:

Thank you so much, Dr. Bazhenova, for this great talk!

MTC 7/19: “Leuk” out for these causes of an elevated white count!

Today, at our inaugural Hillcrest Primary Care Morning Report, we discussed the case of an elderly woman who presented with night sweats and splenomegaly and was found to have a significant leukocytosis. A peripheral blood smear revealed increased bands, metamyelocytes, myelocytes, and basophils. A BCR/ABL1 PCR was sent and returned positive, confirming the diagnosis of chronic myelogenous leukemia. She improved with initiation of imatinib.

With the help of our primary care expert, Dr. Lawrence Ma, a proud alumnus of the residency program, we talked about the most common etiologies of leukocytosis in the outpatient setting. Non-malignant causes of leukocytosis include stress (e.g., trauma), exercise, smoking, medications, acute/chronic infection, chronic inflammation, bone marrow activation, and asplenia. Malignant causes of leukocytosis include chronic myelogenous leukemia (CML), chronic lymphocytic leukemia (CLL), other myeloproliferative/lymphoproliferative disorders, and various solid tumors.

The peripheral blood smear can offer important diagnostic clues. At UCSD and the VA, you can digitally view blood smears using CellaVision. The appearance of blasts should raise concern for an acute leukemia, whereas an increase in more mature blood cells of the myeloid or lymphoid lineage could signal the presence of CML or CLL, respectively. As Dr. Ma pointed out, the decision to refer a patient to Hematology/Oncology is contingent upon a number of factors, including severity/duration of leukocytosis, B symptoms (fevers, night sweats, weight loss), hepatosplenomegaly, lymphadenopathy, bleeding, bruising, and petechiae. Presence of blasts, other immature forms, increased basophils, monomorphic lymphocytosis, and other cell line abnormalities are all suggestive of a hematologic disorder.

Remember, CML is a diagnosis that any primary care physician can make! Classified as a myeloproliferative neoplasm, CML is associated with the t(9;22) translocation (Philadelphia chromosome) and BCR/ABL1 fusion. Diagnosis is confirmed by FISH (for the translocation) and/or PCR (for the BCR/ABL1 fusion transcript). Treatment is with BCR/ABL1-specific tyrosine kinase inhibitors, which include imatinib and dasatinib.

Thank you, Dr. Ma, for everything you do for your patients and for being part of UCSDIM history!

Medical Spanish Word of the Day: el bazo = spleen

MTC 7/8: Mixing things up with some hematology

All hematology cases are exciting, but this morning at Hillcrest, we talked about an EXTRA fascinating case of an elderly gentleman who presented with large intramuscular hematomas and was found to have factor VIII inhibitors.

Our amazing hematologist, Dr. Jenny Zhou, joined us remotely from the UCSD Hemophilia and Thrombosis Treatment Center. We used this case to discuss important historical and exam features that help distinguish thrombocytopenia (or platelet dysfunction) from coagulopathy (clotting factor deficiency or inhibitor formation). Personal and family history of bleeding are important clues that help determine whether the disorder is inherited or acquired. We concluded that platelet problems are prone to producing petechiae and mucocutaneous bleeding, whereas coagulopathies can cause considerable bleeding into deep tissues (e.g., muscles, joints). We took a moment to review the coagulation cascade. The differential for bleeding diathesis will depend on whether PT/INR, PTT, or both are elevated (see Slide 2). We also discussed the role of a mixing study, which helps us distinguish between factor deficiency and inhibitor activity.

Finally, we would like to remind everyone that much of the information we covered today is also available in your handbook. You can find an UPDATED version of the handbook here. For instance, some useful diagrams related to today’s topic can be found on pages 118-119 of the updated handbook. Thank you, Dr. Zhou, for joining us today!

Medical Spanish Word of the Day: la hemorragia, el sangrado = bleeding

VA Morning Report 4/27 – Cold Agglutinin Disease in B-cell ALL

This morning at the VA our stellar Med/Peds senior, Dr. Alexis Quade, presented a case of a 40-year-old man who came into the hospital with subacute fatigue, weakness and dyspnea. The most striking finding on his initial work up was the CBC: Hgb 4.2, Plts 116, and WBC 45 with 88% lymphocytes on his differential. He discussed further work-up of his acute anemia, including studies to evaluate hemolysis. The patient’s peripheral smear had marked red blood cell agglutination into irregular clumps. The blood bank then called the team with an urgent finding: the patient’s Direct Coombs test was C3 positive, IgG negate. He discussed the difference between “warm” (IgG) and “cold” (IgM-complement) autoimmune hemolytic anemia. We were lucky to have our expert discussant, Dr. Soo Park from hematology/oncology, on site to help us navigate testing and its implications. Some of the key take home points about cold agglutinin disease:

  • Causes autoimmune hemolytic anemia when IgM recognize antigens on RBCs at temps below normal core body temp cause agglutination and extravascular, complement-mediated hemolysis
  • Can be secondary to underlying disease (e.g. infection, malignancy)
  • Treatment: transfusion (warmed), avoid cold environment, treat underlying disease, plasmapheresis (severe disease)

Additional work up with flow cytometry and bone marrow biopsy revealed that the patient had acute B-cell lymphoblastic leukemia. This disease has a bimodal distribution and usually presents in children or those over 60 years old. It is important to test for the Philadelphia chromosome translocation as this has major impact on the treatment regimen. Unfortunately, our patient was Ph – and therefore not a candidate for tyrosine kinase inhibitor therapy. He is instead being treated with CALGB chemo regimen, including intrathecal methotrexate and cytarabine. We discussed the role of pre-treatment sperm banking prior to initiation for fertility presentation, as well as the need for intrathecal prophylaxis.

Thank you to Dr. Park for all her clinical pearls as we worked through this complex and interesting case.

Jacobs Conference: Peripheral Smears!

Today in our Jacobs afternoon conference, Dr. Tiffany Tanaka gave a very practical, case-based talk on how to read peripheral blood smears as well as common findings for platelets and leukocytes. She gave a primer on hematopoietic lineages and differentiation, how to read a peripheral smear systematically, and some common, high-yield findings that are often tested on boards. Special thanks to her for helping to teach not one, but two conferences today!!

Morning Report 10/27–Thrombocytopenia

Today we discussed a case of thrombocytopenia with our expert discussant hematologist oncologist Dr. Tanaka. We discussed a case in which a patient with CLL developed severe thrombocytopenia. We discussed ruling out pseudothrombocytopenia when evaluating thrombocytopenia. This is caused by the anticoagulant EDTA in the blood collection tube and can be fixed by using a tube with citrate or heparin. We then broke down thrombocytopenia causes into three main buckets underproduction, splenic sequestration and peripheral destruction. The final diagnosis for our patient was immune mediated platelet destruction secondary to CLL.

Morning Report 9/17: Sickle Cell VOC

September is Sickle Cell Awareness Month and this morning Alex Sykes, one of our awesome R2s, presented a case of a 26-year old man with homozygous sickle cell disease who presented with acute hip pain. We were lucky to have the patient’s hematologist, UCSD’s Dr. Srila Gopal, join us as an expert discussant. We covered the various genetic variants of sickle cell spectrum as we reviewed the patient’s electrophoresis (note that the reason he has any Hb A is due to prior transfusions!) and discussed environmental triggers of vaso-occlusive crises (VOCs). We then covered the why behind the use of hydroxyurea in patient with sickle cell disease and learned about exciting new therapies that are being implemented and researched. Finally, we covered the pathophysiology of vaso-occlusive crisis before learning that our patient’s pain was due to an infarct of the right acetabulum. Many thanks to Dr. Gopal for sharing her vast wisdom with us. 

Jacobs Oncology Conference

Today our fantastic hematologic malignancy expert, Dr. Asimakopoulos, walked us through an interesting case of amyloidosis! We discussed the fine details of what exactly SPEP, UPEP, and Immunofixation are, and how they are useful in the workup of patients with infiltrative protein disease. We also reviewed the most common types of amyloidosis: AL (light chain), AA (chronic inflammatory), and how to distinguish these patients both clinically and with laboratory data. Thank you Dr. Asimakopoulos!

JMC PM Conference – Immune Checkpoint Inhibitor Therapy in Metastatic Colorectal Cancer

This afternoon, Kimberly Kreitinger presented the case of a female in her 50s with a history of metastatic colorectal cancer. The patient has had a course involving treatment for the past 4 years with FOLFOX + Avastin, which was stopped due to HTN, FOLFOX + cetuximab, SBRT to lung and liver lesions, then targeted therapy with trastuzumab and pertuzumab, though demonstrated disease progression. The patient was then considered for immune checkpoint inhibitor therapy with Pembrolizumab, a PD-1 inhibitor.

We discussed the tested indications for the use of ICIs in the treatment of metastatic colorectal cancer. Notably, multiple trials have demonstrated efficacy in prolonging progression free survival and improving overall survival in patients with metastatic CRC, but in patients demonstrated to have either mismatch repair deficiency (MMR-D) or high degrees of microsatellite instability (MSI-H). These trials demonstrated the effectiveness of Pembrolizumab (PD-1 inhibitor), Ipilimumab (a CTLA-4 inhibitor), or the combination of Ipilimumab and nivolumab (PD-1 inhibitor). The rationale behind the use of ICIs in these patients is that those with defective MMR are felt to be prone to indels or frameshift mutations, which may confer increased immunogenicity due to epitope formation.

The patient was found on genomic testing to have microsatellite stability, though demonstrated intermediate levels of tumor mutational burden (TMB) and high levels of Tumor infiltrating lymphocytes (TILs), which may have favorable prognostic profiles with regard to response rates to ICI therapy–active research performed by investigators here at UCSD! Much of this data is preliminary, though provides us with a glimpse of advanced therapies for patients whose disease has progressed beyond standard systemic chemotherapeutic options. Thank you to Dr. Sacco for her expert input and Kim Kreitinger for a great case presentation.

Global Medicine Conference: Autoimmune Hemolytic Anemia

Go RS, Winters JL, Kay NE. How I treat autoimmune hemolytic anemia. Blood. 2017 Jun 1;129(22):2971-2979.

Today Dr. Susan Seav presented a case of bloody diarrhea in a young male. The combination of elevated bilirubin, anemia, and reticulocytes on his blood smear raised concern for underlying autoimmune hemolytic anemia, and the patient was diagnosed with WAIHA secondary to lupus. Up to 10% of patients with WAIHA are DAT/Coombs negative, as with this patient. For more on WAIHA classification and serology, see the figure above from the referenced 2017 Blood review article on the subject. Many thanks to Dr. Fotis Asimakopoulos for serving as our expert discussant!