Thursday, October 30, 2014

New Interesting case at CRBCM

A 47 Year old young Hispanic woman has been referred to us because a 1 year history of abdominal pain and lately has had Hematochezia.  An EGD and colonoscopy were performed and Biopsy in the stomach and the Colon revealed Burkitt Lymphoma. The patient Bone Marrow biopsy is still pending (it is my understanding that a first attempt by the pathologist failed-it should not happen!?  Now patient is asking for general Anesthesia-always a twist to some cases).  Lumbar tap cytology pending!
questions about this case
1.EBV titer?
3.or just plain old Allopurinol
4.Rituxan-HyperCVAD  Vs standerd ALL protocols
5.And now for intrathecal treatment -she is asking for general Anesthesia
6.How to prepare for transplant in patient with lack of Insurance
7. Echo Vs MUGA

Case unfolding, will update you

Sunday, October 26, 2014


certifies that
Mutombo Kankonde, MD
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El Paso, TX 79936
has participated in the enduring material titled

An Innovative Platform to Improve Patient Care in Multiple Myeloma

October 26, 2014
and is awarded 2.00  AMA PRA Category 1 Credit(s)™.
Medscape, LLC designates this enduring material for a maximum of 2.00 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
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For information on applicability and acceptance of continuing education credit for this activity, please consult your professional licensing board.
Certificate Number: 49513617 Cyndi Grimes
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Saturday, October 25, 2014

Imput on Non Hodgkin lymphoma

3 distinct groups of lymphoma
1.Germinal center
2.Activated B cell
3.Primary Mediastinal B cell lymphoma  (closer to Hodgkin disease)

when activated B cell, the prognosis is worse

somatic mutation may also influence outcome

Hans model   CD10     BCL-6   and MUM-1/IRF4   model to determine cell of origin

The Germinal Center B cell  lymphoma respond well to R-EPOCH  (CD10+, BCL-6+, MUM-1 -negative)
whereas the Activated B-cell lymphoma may be better of with Ibrutinib based treatment

Germinal Center responds better to Revlimid than Activated B cell lymphoma

Addition of Velcade allows to conquer the the resistance due to Activated B Cell Lymphoma

Those c-MYC positivity are the worse...and may need upfront transplant...or a clinical trial

Certificate for 'Advances in the Management of Lymphoma and Chronic Lymphocytic Leukemia' at OMedLive

Certificate for 'Advances in the Management of Lymphoma and Chronic Lymphocytic Leukemia' at OMedLive

The power on Pembro! don't leave home without it (in head and neck cancers)!

Why not combine Pembrolizumab and Methotrexate in head and Neck cancer
and break them up into HPV positive and negative. There is reason to believe this combination would be just as powerful as any Cisplatin based treatment.

Pembrolizumab (Trade name Keytruda formerly lambrolizumab;[1]also known as MK-3475) is a drug marketed by Merck that targets the programmed cell death 1 (PD-1) receptor. The drug is intended for use in treating metastatic melanoma.[2][3] Pembrolizumab was invented by Gregory Carven, Hans van Eenennaam and John Dulos at Organon Biosciences which later became Schering Plough Research Institute and then Merck & Co. [4]
On September 4, 2014 the US Food and Drug Administration (FDA) approved Pembrolizumab as a breakthrough therapy. It is approved for use following treatment with ipilimumab, or after treatment with ipilimumab and a BRAF inhibitor in patients who carry a BRAF mutation.[5]"   and "Methorexate  acts by inhibiting the metabolism of folic acid.[3] Methotrexate began to replace the more toxic antifolate aminopterin starting in the 1950s. The drug was originally synthesised by the Indian biochemist Yellapragada Subbarow and clinically developed by the American paediatrician Sidney Farber.[6][7]
It is on the World Health Organization's List of Essential Medicines, a list of the most important medications needed in a basic health system.[8]'

Givem the relative tolerance of these two medications, one must surmise this combination of treatment to be the most tolerable yet effective in disease that seems so virally driven!  We are at the gate of excitement in cancer reaserch and cancer target therapy has just began!
The thing is treatment of locally head and neck cancer has left us hanging,   most people who treat this disease will notice that at the end of radiation  treatment most patient are left with residual mass.  And you keep scratching yourself...should we give additional chemotherapy, watch, of have some form of maintenance therapy?
A lot of patient end up being watched...would maintenance with pembro help survival  ?  How about Pembro+Methotrexate?

Sunday, October 19, 2014


a 39 YEAR old Hispanic woman present to us with T2N1 Breast Cancer, she had a Lumpectomy with sentinel node biopsy, the controlateral breast had a reduction to balance her chest, ER positive PR positive, the immunohistochemical for Her-2 2+ however the FISH did not amplify!  DOES SHE NEED ALND?

This case raises many issues age 39, should we obtain a BRCA gene?
2.frequency of triple positive breast
3.should BRAC be positive should with push for bilateral Mastectomy and Bilateral Oophorectomy
4.should BRCA be positive, what are the proximity genes to look at?
5.what is the frequency of lymphedema post RT
6.Is AC-T the best chemotherapy regimen
7. should T be weekly even though Herceptin is not offered?
8.What is the role of PET in helping decide ALND  Vs RT

but first thing first


For Node-Positive Breast Cancer, Axillary Radiation Is Best

Kate Johnson
June 06, 2013
The AMAROS trial involved patients with cT1-2N0 breast cancer up to 5 cm and clinically node-negative axilla who were undergoing either breast conservation or mastectomy with sentinel lymph node mapping.
Of the patients with positive lymph nodes, 744 went on to receive ALND and 681 received axillary radiotherapy.
Radiotherapy (50 Gy in 25 fractions of 2 Gy, 5 days a week) was started within 12 weeks of surgery, and directed at 3 levels of the axilla and the medial part of the supraclavicular fossa, Dr. Rutgers explained. Levels I and II of the axilla were mandatory and level III was optional.
There were no significant differences in between the radiotherapy and surgery groups at baseline. Median age was 55 to 56 years, and 38% to 42% of the patients were premenopausal. Median tumor size was 17 to 18 mm, and 75% of patients had grade 2 or 3 cancer.
In the cohort, 82% underwent breast conservation and the remainder underwent mastectomy; 90% received systemic treatments. A median of 2 sentinel nodes were removed from each woman.
For patients who received axillary clearance, the sentinel node was the only positive node in 67%; 33% had further node involvement and 8% had 4 or more positive nodes.
After 5 years of follow-up, the axillary recurrence rate was "extremely low" in the surgery and radiotherapy groups (0.54% vs 1.03%), Dr. Rutgers reported.
Because "this was far below what we anticipated, the trial was underpowered for a noninferiority comparison," he explained.
There were no significant differences between the surgery and radiotherapy groups in disease-free survival (86.9% vs 82.7%; P = .1788) or overall survival (93.3% vs 92.5%; P = .3386).
However, 5 years after therapy, the rate of lymphedema in the surgery group was twice that of the radiotherapy group (28% vs 14%).
"The AMAROS trial provides very important evidence that the kind of regional nodal treatment used after a positive sentinel node biopsy will not substantially affect the risk for subsequent regional nodal failure, rates of metastasis-free breast-cancer-specific, or overall survival in most patients," Dr. Recht told Medscape Medical News.
He explained that a more important question than whether to choose radiotherapy is which type to choose.
"Is axillary radiotherapy better at preventing regional nodal failure than just irradiating the breast, which includes the lower portion of the axilla in many individuals?" he asked.
Dr. Recht said that previous studies that compared breast radiotherapy with ALND — such as the"

ASCO recommendation
Kristen Golberg
"The guideline updates three recommendations based on evidence from randomized controlled trials:
• Women without sentinel lymph node (SLN) metastases should not receive axillary lymph node dissection (ALND).
• Most women with 1 to 2 metastatic SLNs planning to receive breast conserving surgery with whole breast radiotherapy should not undergo ALND.
• Women with SLN metastases who will receive mastectomy may be offered ALND.
The guideline updates two groups of recommendations based on cohort studies and/or informal consensus: 
• Women with operable breast cancer and multicentric tumors, and/or DCIS who will have mastectomy, and/or had prior breast and/or axillary surgery, and/or had preoperative/neoadjuvant systemic therapy may be offered sentinel lymph node biopsy (SNB).
• Women who have large or locally advanced invasive breast cancers (tumor size T3/T4), and/or inflammatory breast cancer, and/or DCIS, when breast-conserving surgery is planned, and/or are pregnant should not receive SNB.
The ASCO committee noted that in some cases, evidence was insufficient to update previous recommendations."

Wednesday, October 15, 2014

We have crossed 50,000 reviews!

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Functional proximity of main genes

It is striking to notice that during the daily practice of Medicine, it seems that despite the big number of genes in the cell, there seem that most pathology in human seems to coalesce in just a few abnormalities ultimately.  Disturbances seem to be mostly
1. In Cholesterol or lipid disturbances
2. which are linked to thyroid or endocrine (hormone) disturbances
3.which are linked to Autoimmune diseases
4,linked to vitamins (D) disturbances
5. and linked to neoplastic phenomena, linked to Glucose derangements
6. and to neurologic and psychiatric disturbances...
The only new phenomena that may be separate but linked is Infection because indeed Infection involves a foreign body looking in!  And fight against infection seems to follow cellular pathways which depend of the nature of the infectious agent...with Viral infections involving the mitochondrial process more than bacterial infection...

Yes indeed, we see for example that a patient may have an elevated white blood cell could have an infection, but in most cases, it is an autoimmune disease, usually associated to a thyroid dysfuction and a depressive or anxiety component.

Now this notion that Prostate cancer recurrence may be associated with dyslipidemia...
or that polycystic kidney disease be accompanied by depression.

Disturbances in anexins and other supportive structures are somewhat hidden but their importance remains in full force...Now I can see why so many genes are somewhat or definitively much is left un attended to.   My day to day is globally busy with the few genes that I still have my finger up ready to point!  Even when I see the NF1 gene and many growth gene dancing with the BRAC gene...and that triple negative breast cancer in some race is dancing with autoimmune disease that affect the skin (psoriasis)!

Sunday, October 12, 2014

Where don't we dance enough: managing life span, an independent factor in managing cancer patient, and may increase the cure rate!

Because of limited resources available in research, society falls short in the management of cancer patients.  The notion that cancer patient should be managed by affecting only their driver Mutation has been popular lately and most research has focused on this emphasis.  There is a rush to discovering  the driver mutation in each disease.   The truth is that driver mutation although very effective (ie. BRAF inhibitor) for a short time, are quickly overwhelmed by what we have come to know as "mechanisms of resistance"  The point is that cells are constantly exposed to new environmental stimulants.  And their natural TASK is to die or adapt.  And naturally we try to forget or underestimate the adaptative capability of cells, including neoplastic (cancer) cells.  Cure will remain fleeting until a closer look is taken into these adjustment techniques used by the cancer cells.  and it is within that contest that I bring this statement to your mind:

" that SHC-1 not only opposes IIS but also activates JNK signaling. Loss of shc-1 function results in accelerated aging and enhanced sensitivity to heat, oxidative stress, and heavy metals, whereas expression of human p52Shc rescues the shc-1 mutant phenotype. SHC-1 acts upstream of the insulin/IGF receptor DAF-2 and the PI3 kinase AGE-1 and directly interacts with DAF-2. Moreover, SHC-1 activates JNK signaling by binding to MEK-1 kinase. Both aspects converge on controlling the nuclear translocation and activation of the FOXO transcription factor DAF-16." Elke Neuman-Haeflin et al.

If you are shocked and troubled by the placement of this statement here, you are completely within the norm! but let's go back and recapitulate.   Most cells succumbs to external pressure by cellular environmental stimulations.   Hypoxia, autocrine cytokines, chemicals and minerals end up exciting receptors including VEGFRs  (the MEK is close by).  But really when you speak of the VEGF, you imply SHC1,2 and stimulation of Annexins and from there p52, p42, and the famous p66SHC....then you can understand the above sentence...In Gastric cancer for example,  VEGFR2 is stimulated and therefore the effectiveness of Ramucirumab.  (CYRAMZA.)

Please note that the statement speak about p52 and does not even address the main RAS cofactor p66 which may affect Cyclin D and deplete MCI-1 the main depletor of SHC-1. (through PTPNs)
RAS autophosphorylation driving the cancerous process may be hidden here.

These facts point to the truth that independent of cancer driven mutation, control of these processes must occur concurrently to improve the cure!  cancer deaths are produced by progression of cancer but also involvement of cellular maturation and lifespan determinants that most Oncologist do not measure! (we dance very little away from guidelines (NCCN))...

Saturday, October 11, 2014

Pathogenesis of Neoplastic transformations.

Speculative sources of Neoplastic disease

As we plan Cancer Prevention, it seems logical to target potential mechanisms that likely could initiate the neoplastic process in order to propose logical steps.  And clearly, from a beginner stand of view, and from data screening of various cancer, this task could be daunting.  However major patterns have to be proposed as we examine what works, and what are the main metabolic disturbances in each disease.
*In Kidney cancer for example, Here abnormality in the Von Hippel Lindau gene (gene that promote UBIQUINATION) has supported strongly the involvement of an exaggeration of deficient Hypoxia induced factors (HIF) and related proteins.  This facts lead to the removal of inhibitor forces leading to the expansion of VEGF and PDGF.   It takes blocking the either the the VEGF (Avastin) or blocking the MTOR down the line (Everolimus) to slow down the neoplastic process.   Anything in between may have not been efficient.   Hypoxic conditions often found in patient with obesity (associated with sleep Apnea) may favor the frequency of this disease.   The involvement of VEGF explain the importance of abnormal Angiogenesis in this disease...the tumor is bloody ...Therefore, optimizing Oxygenation (CPAP use in obese patient with sleep Apnea), decreasing or impairing VEGF, could have significant prevention use.   Optimizing Iron level may also have a positive impact should studies initiated here further support that iron deficiency may exacerbate the various cellular metabolites.   Interferon and IL-2 should be consider under this light (as to their effect on the VEGF-MTOR  axe. The involvement of Ubiquination beg the question on whether Velcade and anti-TNF related compound may add to the therapy in Kidney cancer.  One thing is for sure, all cancerous transformation try to escape the immune system, and Pembrolizumab could be discussed further within the contest of this disease!   our knowledge is rapidly expanding.

*In Lung Cancer, the neoplastic transformation is diverse since some non smokers are known to develop the disease.  Here we believe that diet based on high levels of anti-oxidant without sufficient compensatory iron (iron deficiency in women particularly) and HIF gene isoforms may lead to  chronic intoxication triggering once again EGFR/VEGF expansion.   Susceptibility of these cancers to Cetuximab/ERBITUX strongly support this hypothesis. Detoxification may also be influenced by CYP1A1 and GSTM1.

In standard lung cancer however, not only HIF is involved, but there is now increasing suspicion that alterations at the MDM-2 has entered the possibility of initiating the disease process forcing further Ubiquination or intervening at some point, affecting the P53, c-MYC, NPM1 and even prot 14-3-3 ("Phosphorylation of Cdc25C by CDS1 and CHK1 creates a binding site for the 14-3-3 family of phosphoserine binding proteins. Binding of 14-3-3 has little effect on Cdc25C activity, and it is believed that 14-3-3 regulates Cdc25C by sequestering it to the cytoplasm, thereby preventing the interactions with CycB-Cdk1 that are localized to the nucleus at the G2/M transition.[wikipedia) effect on Ubiquitination should be re-emphasized.   With stimulation and amplification of the EGFR/VEGF come the importance of ALK, BRAF, again factors that have enterec lung cancer therapeutics since agents active here have become available (to be continued)

Friday, October 10, 2014

Warsaw Indiana, an interesting case

We are back in Warsaw Indiana completing obligations here for CRBCM.
This exercise also expose us to local pathology and ways they are managed by local Oncologist.
An interesting case encounter here is that of a 22 year young mother who had 2 c-sections and was referred for Menorrhagia, she had a Biopsy of the Uterus, and a Von-Willebrand screen suggested very elevated Factor VIII  (3 times the upper limit).    She is obese and suffers from Hypothyroidism.  Now elevation of Factor VIII has been identified as an independent factor determining an Hypercoagulable state.  We may soon be quantifying related gene.  This Hypercoagulable state is however confusing because it is indeed associated with higher risk of stroke and Coronary events.  However, independent of thrombotic event, does it really require Anti-Coagulation for life?
The patient has been advised Aspirin,  do we  justify Xarelto at preventive dosage?  Should weight loss be a sufficient intervention, should we look for coexisting Hercoagulable factor such as Factor V leyden, or Homocystein for that matter...we are checking TSH level of course...Elimination of this factor is associated with certain Blood Group,  should we type and cross ?  Very puzzling case indeed!  What are the genes proximate to this gene?
familial predisposition has been appreciated by the presence of BRCA1 and BRCA2
but increasingly we find young women with breast cancers who do not carry the mutation expected.  By their age and family history, we know there must be a genetic predisposition for the particular cancer of the breast to occur.
1.Mutation in the genes regulating or acting in the vicinity of the BRCA.
For medicine to advance and allow better use of limited resources and decrease the burden of side effects for our patients, It would be critical that new sets of genes enter the standard detection/category testing in the management of Breast Cancer. There are over 100 Mutations knwon!

2As far as BRCA2 is concerned, interaction with RAD51 has been suggested.   Ween et al:"versican and hyaluronan (HA) which interacts with the HA receptor, CD44, have been shown to play critical roles in ovarian cancer metastasis."  These molecule states (isoforms) have been found to be increasingly affected by interaction with growth factors   TGF and even PDGF.  (early detection of metastatic disease).  They should enter biomarker testing.

3.BRCAs are "wild gene"  first because there are hundred of these Mutations
and also because Wikipidea describes multiple various interactions:

"BRCA1 has been shown to interact with

Monday, October 6, 2014

Getting more training in research, full schedule.....this is my outlook Calendar

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Saturday, October 4, 2014

Treatment in advanced Head and neck cancer

adding Taxane does not change survival
question maintenance of Cetuximab
weekly Taxol - carbo
weekly Methotrexate
Gemzar - Cisplatin

for early stage of course
------------------------------chemotherapy and weekly Cisplatin +/-Cetuximab
or RT with Cetuximab