Jacobs Oncology Conference: Colon Cancer Screening

Thank you to Dr Patel for joining us at Jacobs Oncology Conference today and reviewing colon cancer screening!

Increased Incidence in Colon Cancer Diagnosis in Ages <50 years! Left-sided colorectal cancer rates have been increasing in the population less than 50 years, therefore some new guidelines suggest starting screening at 45 years of age. The incidence is increasing every year. This is not completely understood, however many environmental factors may be contributing to this increase!

Environmental Risk Factors for Colorectal Cancer: Red meat intake (RR 1.5), Obesity (RR 1.5), Alcohol consumption >4 drinks/week (RR 1.4), Cigarette use (RR 1.5)

Screening Modalities: FOBT/FIT testing (quick to use, no dietary restrictions, inexpensive, however lacks sensitivity for early disease, requires annual administration and a positive results needs a colonoscopy), Stool DNA Tests (non invasive, 90% sensitive, however requires 24 hours stool collection and may still lead to false negatives), Flex sigmoidoscopy, and colonoscopy (can detect AND remove precancerous growths, less frequent testing, but more invasive, resource intensive, and completion is low)

SCREENING: AVERAGE RISK patient should be screened from ages 50-75 years

-Annual Screening with high-sensitivity FOBT/FIT (low sensitivity)

-Annual Screening with stool DNA tests (Cologuard)

-Sigmoidoscopy every 5 years, high sensitivity FOBT every 3 years

-Screening colonoscopy every 10 years

SCREENING: POSITIVE FAMILY HISTORY (first degree relative or multiple second degree relatives)

-Colonoscopy every 5 years starting at age 40 ears or ten years before the youngest case in the immediate family

Jacobs Oncology Conference: Sickle Cell Disease

Today in Jacobs Oncology Conference, we had Dr Gopal go through a case presentation of a 21 yo W with sickle cell disease (SS) who presents for one day of back and leg pain. Here are the main takeaways!

Hemoglobin Electrophoresis

The higher the percentage of S hemoglobin, the more sever the symptoms. This is typically SS disease and S-beta-thal-0 where SS percentages >95%. These patients are typically fairly anemic.

Milder forms of sickle cell disease include SC disease and S-beta+thal (less likely to be as anemic and have as many complications as patients with SS or S-beta-thal-0 disease)

Hydroxyurea increases the levels of Hgb F (fetal hemoglobin). HgbF levels of 20-30% have significant mortality benefits.

Treatment of Vaso-Occlusive Crisis

Hydration- just try to maintain normal hydration levels, can even avoid IVF if patients are drinking well. Consider using hypotonic fluids for sickle cell patients. Do NOT over-hydrate as this can predispose them to ACS.

Transfusion Indications: Do not transfuse for asymptomatic anemia (even if Hgb <7). Transfusion during an acute pain crisis can actually worsen symptoms and create more antibodies. Transfusion should only be considered if there are symptoms of anemia or signs of end organ damage.

Acute Chest Syndrome

Diagnosis: New pulmonary infiltrate + (one of the following) fever, cough/tachypnea/SOB/work of breathing, rales/wheezing, chest pain, decrease in baseline O2 sat >2% on RA. ACS encompasses a spectrum of disease. Patients with pneumonia may be indistinguishable from ACS therefore they should be treated for ACS

Treatment: Exchange transfusion (or simple transfusion), antibiotics, avoid fluid overload, and IS!

Indications for Exchange Transfusion: stroke, ACS, or severe acute cholestasis. Patients with anemia due to SCD can also benefit from simple transfusion if exchange cannot be done. Avoid simple transfusions for patients with normal Hgb as this can worsen viscosity (ie patients with SC disease and normal Hgb)

Jacobs Oncology Conference: Colon Cancer

Today Dr Vu did an overview of colorectal cancer! Here are the main takeaway points!

Diagnosis

First step is to perform a colonoscopy to obtain histopathology. Differentiate between colon v rectal cancer. Typically anything in 12 cm from the rectal verge is considered rectal cancer. This is important to distinguish because this distinction changes treatment and recurrence.

Next step would to obtain imaging to provide staging. Obtain a CT Chest and CT A/P as three main sites of metastases are lung, liver and lymph nodes due to the lymphatic spread of malignant cells.

Genetic Testing: ALL patients (even without family history) with new diagnosis of colon cancer should obtain genetic testing for mismatch repair genes, which can be either hereditary (germline) or sporadic. Prevalence of mutations increases with early stages of disease. This has to do with an increase in immune response with these mismatch repair mutations that keep the “tumor at bay”.

Treatment

Rectal tumor: Need an MRI of pelvis to create a surgical plan. Key is to do as much treatment up front before surgery to preserve tissue, which includes chemo AND radiation.

Colon tumor: Who do you call? Medical Oncology and Colorectal Surgery (not Surgical Oncology)

Stage 1 (very small and shallow): endoscopic removal

Stage 2: surgical removal +/- chemotherapy afterwards (however that is controversial and you do not give with patients with mismatch repair mutations)

Stage 3 (in the lymph nodes): Surgery + adjuvant chemotherapy (within two months)

Stage 4 (metastatic): surgery + systemic treatment (and sometimes resection of metastases for oligometastatic disease)

Surveillance

Scans performed every 6 months for the next two years (as the risk of recurrence is highest early on), circulating tumor DNA is tested routinely, and a colonoscopy at one year. After the 5 year mark, cancer is considered “cured”.

Recurrence

Rectal cancer is more likely to recur in the same area however colon cancer more likely to recur elsewhere in the body.

Jacobs Onc Conference: Complications of AML

Acute Myeloid Leukemia (AML) in Children and Teens - Together

Cytopenias: Anemia, neutropenia and thrombocytopenia are commonly seen.

Treatment- Supportive transfusions and bacterial, fungal and viral ppx

Hyperleukocytosis: WBC >50-100 x 10^9/L. Symptomatic hyperleukocytosis (Leukostasis) typically presents with respiratory or neurological symptoms and constitutes a medical emergency! An absolute myeloblast count approaching 100,000×10^9/L is a medical emergency even if the patient is asymptomatic

Treatment-Leukapheresis (call Nephrology), induction chemotherapy, hydroxyurea

Tumor Lysis Syndrome: Hyperphosphatemia, hypocalcemia, hyperuricemia, hyperkalemia, renal insufficiency, elevated LDH

Treatment- maintenance fluids +/- lasix (goal UOP ~150 cc/hr), allopurinol and rasburicase

Jacobs Onc Conference: Prostate CA

Today, Dr McKay reviewed with us the classification and treatment of prostate cancer!

Classifying Localized Prostate Cancer

Localized prostate cancer is broken up into low risk (or even low-low risk), intermediate, and high risk. Classifications are based on the Gleason Score which is made by histopathological evaluation of the cancerous cells. The higher the score=the more undifferentiated the cells=the higher the risk! It is also broken down by PSA levels with <10 being low risk, 10-20 being intermediate risk and >20 being high risk. You can also use MP MRI to further characterize extent of tumor which will also impact staging.

Treatment for Localized Prostate Cancer

Low Risk= typically active surveillance but patients may also opt for radical prostatectomy or radiation (external beam or seeds)

Intermediate Risk=radical prostatectomy OR external beam radiation (EBRT) +/- androgen deprivation therapy (ADT)

High Risk= Radical prostatectomy+ EBRT+ ADT

Androgen Deprivation Therapy

ADT’s goal is to reduce testosterone <50 as testosterone binds to androgen receptors in the cancerous prostate cell leading to dimerization, translocation into the nucleus and ultimately cell growth. There are three mechanisms of drugs to suppress testosterone levels. Side Effects include: fatigue, weight gain, decreased muscle mass, decreased bone mass, elevated cholesterol and possible cognitive effects

(1) LHRH agonists or antagonists: LHRH agonists will create consistent agonism which eventually will turn off the axis of LHRH release leading to decreased testosterone production from the testicles HOWEVER it will initially cause a transient RISE in testosterone. Antagonists will immediately decrease testosterone levels without a transient rise in testosterone. Consider antagonists if the patient already has obstructive symptoms from PCA or spinal cord compression. This is “castration therapy”

(2) Androgen Receptor Blockade: This class blocks testosterone from binding the androgen receptor, so you will actually see a rise in testosterone levels however they are unable to cause downstream effects on the prostate cancer cell.

(3) CYP17 inhibitors: These medications block the conversion of mineralocorticoid and glucocorticoid to sex hormones produced by the adrenals. Since only 10% of the body’s testosterone is made in the adrenals, these medication are combined with other ADT therapies. Side effects include mineralocorticoid excess (hypokalemia, hypertension, edema)

Other Classifications of Prostate Cancer include “Biochemical Recurrence” which is an elevation in PSA after treatment of localized disease without evidence of metastatic disease, “Metastatic Hormone Sensitive” which still responds to ADDT (+an additional agent), and “Metastatic Hormone Resistant” where multiple drug regimens (including chemotherapy) would be needed and this no longer responds to ADT

Jacobs EBM Conference!

We had to great EBM presentations today by our Jacobs Wards residents!

Portal Vein Thrombosis: Should we anticoagulate? (Brad Fairfield PGY3)

When considering treatment of PVT, treatment goals are to prevent clot progression and thus worsening portal hypertension or inhibit transplant candidacy

Stronger evidence for treating cirrhosis related PVT:  Mesenteric ischemia or risk of mesenteric ischemia (SMV involvement), Transplant listed

Stronger evidence against treatment:  Malignancy associated (TIV), chronic PVT, contraindications to AC

Bleeding complications do occur in patients treated with AC, though not at significantly higher rates than patients not treated with AC

Overall low quality of evidence, but data seems to suggest that AC should be considered in all patients with cirrhosis related PVT and would favor initiation in patients without general AC contraindications

Aspiration Pneumonia: Do we always need to cover for anaerobes? (Armando Martinez PGY3)

There has been a decrease prevalence of anaerobes in sputum cultures in patients with suspected aspiration pneumonia over the years, which is suspected to be due to possible improvement in oral hygiene

While anaerobic coverage was typically used for presumed aspiration pneumonia, studies have not shown any benefit with antibiotic regimens that include anaerobic coverage

In 2019, the IDSA and ATS released an updated statement recommending against routinely adding coverage against anaerobes in suspected aspiration pneumonia unless empyema or lung abscess is present

Check out this great review article on Aspiration Pneumonia (thanks to Erica Feldman!)

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!!

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!

Jacobs PM Conference – Acute Anaphylaxis

This afternoon, Sophie Cannon presented an interesting case of a female in her 30s with a history of chronic urticaria who presented in respiratory distress, tachycardia and throat swelling following the ingestion of a meal prepared at a restaurant. A similar event had happened previously, months ago though the symptoms were not as severe, and self resolved. This prompted the discussion of upfront recognition and treatment of patients whose presentations are concerning for anaphylaxis, the diagnosis of which is purely clinical, and can be made in the following scenarios: Screen Shot 2020-02-20 at 8.02.14 AM.png

We also reviewed the pathophysiology of the various mechanisms by which anaphylaxis occurs. Most are likely familiar with the canonical IGE mediated pathways, Which upon re-exposure, allergen-specific IgE antibodies bind to allergens and form allergen-specific IgE immune complexes, which then activate mast cells and basophils, causing degranulation and release of preformed histamine, leukotriene, prostaglandins, and platelet activating factor. There are several additional pathways worth mentioning, including the non-IgE pathways involving IgG, cytokine release response pathways involving IL-6, IL-1B, and TNFa, mixed CRR/IgE pathways, as well as the direct complement C5a activating pathways. Screen Shot 2020-02-20 at 8.09.01 AM.png

The patient was ultimately treated with IM Epinephrine, which prompted resolution of the patient’s respiratory symptoms, glucocorticoids to help prevent biphasic anaphylaxis, as well as antihistamines to treat the patient’s pruritis and skin manifestations. Thank you to Sophie and Dr. Broide for a great case, and fantastic teaching!

Take Home Points: 

  1. Anaphylaxis is a clinical diagnosis; early recognition and empiric treatment can prevent respiratory and cardiovascular collapse and death
  2. Multiple mechanisms lead to “anaphylaxis,” including those that are mediated by T-cells and macrophages, which may present with a sepsis-like presentation, due to release of pro-inflammatory cytokines IL-6, IL-1B, and TNF-a
  3. IM Epinephrine is the gold standard therapy upfront and is the only measure that has been shown to effectively treat respiratory compromise associated with anaphylaxis. Glucocorticoids, antihistamines, and leukotriene modulators are all adjunct strategies and should not be used in place of epinephrine. Caution should be used when considering IV Bolus epinephrine, as outcomes have not been demonstrated to be superior, but have instead been linked to cardiovascular complications such as MI/Stroke.

Figures were adapted from Wilfox et al, Journal of Asthma and Allergy, 2018

Jacobs PM Report–10/16/19–EBM with Dr. Lizzy Hastie

For our PM report at JMC this Wed, R2 Lizzy Hastie led us through an interactive worksheet, a review of the literature on the pros and cons of the LRINEC score for identifying Necrotizing Fasciitis, AND a photo quiz of soft tissue infections.  Take home point, as with any tool, clinical judgment is paramount! Trust your instincts and involve surgery early if nec fasc is on your differential.  Early in the course, the labs may not yield a high LRINEC score.