Cancer Screening - US Preventive Services Task Force (USPSTF) guidelines

     As the saying goes - "Awareness is Power in a world where information is everywhere", lets quickly learn the USPSTF recommended guidelines for Cancer screening

CANCER	SCREENING MODALITY	AGE GROUP
Breast Cancer	Biennial Mammography	Women aged 50 to 74 yrs
Cervical Cancer	Cervical cytology every 3yrs   Cervical cytology every 3 yrs  or High risk HPV(hrHPV) testing every 5 yrs or hrHPV testing in combination with cytology every 5yrs (cotesting)	Women aged 21 to 29 yrs  Women aged 30 to 65 yrs
Lung Cancer	Annual Low dose CT chest (who have a 20 pack-year smoking history and currently smoke/quit within past 15 yrs)	Adults aged 50 to 80 yrs
Colorectal Cancer	Colonoscopy screening every 10 yrs Flexible sigmoidoscopy every 5 yrs Computed tomography colonography every 5 yrs High-sensitivity guaiac fecal occult blood test (HSgFOBT) or fecal immunochemical test (FIT) every yr Stool DNA-FIT every 1 to 3 yrs	Adults aged 45 to 75 yrs

P.S. - USPSTF now recommends screening for Colorectal cancer in adults aged 45 to 75 years

- Padma Sri Katikaneni                                                                                                                       

                  

COMMON METASTASES - MNEMONICS

SITE OF METASTASIS                              PRIMARY TUMOUR 

BRAIN                                                                    Lots of Bad Stuff Kill microGlia

                                                                                 Lung, Breast, Skin (melanoma), Kidney, GI(colon)

LIVER                                                                     Cancer Sometimes Penetrates Big Liver   

                                                                                 Colon, Stomach, Pancreas, Breast, Lung 

BONE                                                                      Permanently Relocated Tumours Like Bones

                                                                                 Prostate, Renal, Thyroid, Lungs, Breast

     

P.S. - FOUR CARCINOMAS ROUTE HEMATOGENOUSLY! 

        (Follicular carcinoma thyroid, Choriocarcinoma, Renal cell carcinoma, Hepatocellular Carcinoma)

Hope these mnemonics help!

Feel free to add any more fun mnemonics :)

- Padma Sri Katikaneni

Atrial myxoma song

By Huzefa Bhopalwala

Mnemonic for cancers which have “BRAF” gain of function mutation

Hello everyone ! 

Mnemonic : 

A Factor A Day Keeps Colon Cancer Away

Protective Factors For Colon Carcinoma

A - Aspirin,vitamin A 
B - Bisphosphonates
C - Calcium, Coffee, vitamin C
D - Dietary Fiber
E - vitamin E
F - Fruits
G - Green Vegetables

Olanzapine dose in CINV

Hi!

Olanzapine, an anti-psychotic, has been used in the patients of cancer for its beneficial effects on chemotherapy-induced nausea and vomiting (CINV) at a dose of 10 mg due to its anti-emetic action (neurotransmitter blockade at serotonin and dopamine receptors).

But due to its major adverse impact of daytime sedation, recent studies and randomized controlled trials have concluded its revised dose to be 5 mg for CINV.

To be noted here that the anti-emetic use of olanzapine is still off label, an unlicensed drug used for this purpose.

That's all

- Jaskunwar Singh

Retinoic Acid and Malignancy

Hello Awesomites !

This is going to be short post.
Relevant for exams.

All trans retinoic acid is used in APML (ACUTE PROMYELOCYTIC LEUKEMIA)

Cis retinoic acid and derivatives like 13-cis-retinoic acid (13-cRA) reduces second aerodigestive tract tumors in patients with resected head and neck cancers.
13-cis RA is used in Neuroblastoma.

Happy studying.
-Upasana Y.

Differentiation syndrome

Hello Awesomites !

AML (M3) also known as acute promyelocytic leukemia.
The drug is ATRA+As2o3 ( All trans retinoic acid +arsenic trioxide).

After few days from therapy :-
unexplained fever,
acute respiratory distress with interstitial pulmonary infiltrates,
and/or a vascular capillary leak syndrome
leading to acute renal failure.

Suspect :-

Differentiation syndrome (DS), formerly known as retinoic acid syndrome, is the main life-threatening complication of therapy with differentiating agents (all-trans retinoic acid [ATRA] or arsenic trioxide [ATO]) in patients with acute promyelocytic leukemia (APL).

The differentiation of leukemic blasts and promyelocytes induced by ATRA and/or ATO may lead to cellular migration, endothelial activation, and release of interleukins and vascular factors responsible of tissue damage.

 Roughly one quarter of patients with APL undergoing induction therapy will develop the DS.

Treatment -
Early therapy with intravenous corticosteroids. The use of invasive diagnostic techniques, such as bronchoscopy and bronchoalveolar lavage or lung biopsy, is not usually required in patients with suspected DS and respiratory distress with lung infiltrates.
Be careful with invasive procedure as these patients have concomitant coagulopathy (DIC like state)

The early administration of high-dose dexamethasone at the onset of the first signs or symptoms of DS is crucial, since it appears to dramatically reduce mortality of this complication.

 HAPPY STUDYING :)
-Upasana Y.

Protein gap

The gamma gap aka paraprotein gap or protein gap is the difference between total serum proteins and albumin measured from a comprehensive metabolic panel.

Albumin accounts for the majority of total serum protein.

Viral infections, plasma cell malignancies, or autoimmune conditions there is an excess of immunoglobulins, raising the total amount of serum protein independent of albumin.

The gamma gap is typically considered to be elevated if it is above 4 g/dL.

In the right clinical context, gamma gap should be worked up with SPEP, UPEP, and a serum free light chain assay.

Random exercise: Calculate the protein gap.
Total protein 8.9 g/dL (normal 6.4-8.3 g/dL)
Albumin is 3.6 g/dL (normal 3.4-4.8 g/dL)

That's all!

-IkaN

Burkitt’s Lymphoma types

There are three types of Burkitt’s Lymphoma: Endemic (African), Sporadic  (non-endemic) and immunodeficiency-associated.

Molecular mayhem - AML relapse after HSCT

For many hematological disorders including AML, CLL, ALL HSCT is the only viable therapeutic option when cytogenetics are not conducive for chemotherapeutic agents. However subsequent relapses are not uncommon which are due to subtle molecular alterations because of underlying and acquired mutations.

Simpson's Grading for Brain Tumors.

Hello Everyone!

So my Neurosurgery residency diaries continue and I continue sharing as I learn.

Learnt about the Grades of Tumor resection while operating on a Glioma.

These are Simpsons Grades of Tumor resection and are correlated as the degree of surgical resection completeness with with symptomatic recurrence. 

Grade I-complete removal including resection of underlying bone and associated dura.

9% symptomatic recurrence at 10 years

Grade II-complete removal and coagulation of dural attachment.

19% symptomatic recurrence at 10 years

Grade III-complete removal without resection of dura or coagulation.

29% symptomatic recurrence at 10 years

Grade IV-subtotal resection of the tumor.

44% symptomatic recurrence at 10 years

Grade V-simple decompression with or without biopsy

100% symptomatic recurrence at 10 years.

That was it!

Let's Learn Together!

-Medha Vyas 

Difference Between Solitary and Singular Brain Metastasis.

Hello Guys!

So we were operating on a metastatic brain lesion the other day when My Consultant happened to ask me the question-  " What is the difference between Solitary and Singular Brain Metastasis?" Well I happened to have a vague idea and managed to blabber something, the actual definition goes as-

• A solitary brain metastasis is defined as the only known metastasis of a tumour in the whole body which happens to be
localised in the central nervous system.

• A singular brain metastasis is defined as a single cerebral metastasis with additional metastases in other organ systems.

Well it's a small nugget, may save you some embarrassing moments.

Let's Learn Together!
-Medha Vyas.

Paroxysmal nocturnal hemoglobinuria

1)PNH originates from an acquired mutation ( frame-shift that creates a premature stop codon) in a myeloid stem cell, the acquired mutation in PNH occurs in the PIGA gene which is responsible for the first step in the synthesis of the GPI anchor that attaches CD55 and CD59 to the cell surface.

2)Complement detects self vs nonself cells by these complement inhibitors. Function of these complement inhibitors is to:

3)In the absence of these inhibitors, complement proteins bind cell membranes of our own cells and through the alternative complement pathway can lyse self-cells.

4)CD55/DAF decrease → More C3 convertase→Increase C3b→Increase opsonization→Extra Vascular Hemolysis.

   CD59/MIRL decrease→More MAC→Intra Vascular Hemolysis.


5)Why nocturnal hemoglobinuria- hemolysis occurs throughout day but its more at night because:   (a)Increased hemolysis in night due to respiratory acidosis(Shallow breathing).
 (b)Overnight concentration of urine is more and hemoglobinuria is clearly evident.

6)Diagnosis:(a)Flow cytometry- decrease CD55 and CD59 levels.
                     (b)HAM test-confirmatory.
                     (c)Direct coombs test-Negative (Helps to differentiate PNH and AIHA- its positive in AIHA)                                                                           

7)Treatment: 

(a)Ravulizumab- long acting C5 complement inhibitor

(b)Eculizumab- It is an Antibody to C5 and prevents its clevage to C5a and C5b, so no MAC. Ravulizumab has a half life that is three to four times longer than eculizumab.

-Srikar Sama

SOURCE: UpToDate, Uworld.

Warfarin Induced Skin Necrosis

Warfarin-induced skin necrosis is a complication of warfarin therapy in which the patient develops demarcated areas of purpura and necrosis of skin including the extremities, breasts, trunk, or penis.

Mechanism:
1)Mechanism of action of Warfarin is it inhibits VitK epoxide reductase,so there is decrease in synthesis of VitK dependent factors - (factors II, VII, IX, and X) and natural anticoagulants (protein S and protein C).


2)Now no new clotting factors are produced but the old circulating clotting factors are still present (warfarin has no effect on already circulating clotting factors).


3)Among the factors II, VII, IX, X, ProteinC that are already present,ProteinC has the shortest half life,So ProteinC is depleted more rapidly than the others.


4)Now there is no anticoagulant in the body to oppose the action of already present clotting factors,so there will be initial coagulation till factors II, VII, IX, X gets depleted i.e till their half lives are completed.


5)This initial coagulation occurs in dermal vasculature which causes Skin Necrosis.

Prevention:
Overlapping of warfarin with heparin during the first several days of warfarin administration(if Heparin is given along with warfarin, this prevents functioning of circulating factors since heparin inhibits the activity of circulating thrombin and factorXa) and then warfarin is continued for long term therapy.


Source: UpToDate, First Aid.

-Srikar Sama

Ingenious Immune System

Hello friends, today let's take a moment to appreciate how amazing is our immune system.

In our immune system, just like any regular car, there are brakes in place to regulate its working. Removing brakes can certainly enhance its function which underlies the concept of immune checkpoint blockade.

Two such molecules on the surface of T-cells are CTLA-4(Cytotoxic T-lymphocyte associated protein 4) and PD-1(Programmed cell death protein 1).

When CTLA-4 binds to its ligands B7-1 and B7-2 which are often expressed in increased numbers on tumor cells it results in inhibition of T-cells and hence allowing tumor cells to evade apoptosis and survive.

Similarly when PD-1 binds to PD-L1on tumor cells inhibitory signals are relayed to T-cells.

In macrophages signal, regulatory protein alpha mediates inhibitory signals on interacting with CD47 on tumor cells.

In NK-cells KIR2DL1(killer cell immunoglobulin-like receptor 2DL1) mediates inhibitory signals.

So blocking these inhibitory signals by monoclonal antibodies can remove "brakes" on the immune system ultimately enhancing their ability to kill tumor cells.

Approved antibodies include:

Anti CTLA-4-Ipilimumab

Anti PD-1-Nivolumab, Pembrolizumab

Anti PD-L1-Avelumab,Durvalumab

Kirtan Patolia

Cryptic conundrum in ET: Thrombosis or bleeding?

In essential thrombocytosis, contrary to what might be surmised, bleeding is more of threat than thrombosis.

This is because high platelet count especially above 1 million/mm3 cause acquired von willebrand disease, much like type 2b von willebrand disease, where excessive affinity of vWF for platelet Gpib result in excessive removal of platelet-vWF complex by spleen results in  thrombocytopenia and loss of high molecular weight vWF multimers.

However, incidence of erythromelalgia , transient ischemic attack and other microvascular events are also high in patients with essential thrombocytosis.

Pretty complex and contradictory, right?

- Kirtan Patolia ( BJ medical college).

Zebra series: Stauffer syndrome

Hello,

I'll be talking about Stauffer syndrome today!

Why is the level of Vitamin B12 increased in CML?

Why is the level of Vitamin B12 increased in Chronic Myeloid Leukemia (CML)?

Pathophysiology: The transport of vitamin B12 in the blood as well as hepatic uptake require the presence of transcobalamins (TCBs).

TCB types I (TCB I) and III (TCB III) ensure the binding of ∼80% of circulating vitamin B12.

Warfarin and Newer Oral Anticoagulants (NOACs) notes

Hey guys!
These are my notes from Harrison on Warfarin and Newer Oral Anticoagulants (NOACs).