RENAL CANCER & TRANSPLANTrename
zwinthrop's version from 2015-05-18 18:27
|Renal Carcinoma||MNEMONIC: 3 letters = Chromosome 3 = Triad (hematuria, flank pain, mass). |
GENERAL: Most common primary renal malignancy. RISKS: Men 50-70, Smoking, Obesity, HTN.
GENETICS: Loss of VHL (3P) Tumor Suppressor --> Increased IGF-1 --> Increased HIF --> Increased VEGF/PDGF
Clear Cell Carcinoma = 70-80%, originates in PCT, polygonal clear cells filled with lipids/carbs, more sporadic than familial (5%). VHL Syndrome associated.
Papillary Carcinoma = 10-15%, Originates in DCT, cuboidal/low columnar cells, papillary growth, foam cells in papillary cores, Psammoma bodies, associated with Trisomy 7/17 and loss of Y chromosome.
CLINICAL: Edema (varicocele due to blocked drainage of spermatic vein (left kidney)), Paraneoplastic syndromes: EPO (polycythemia), Renin (HTN), PTHrp (hyper Ca2+), ACTH (Cushing syndrome). Metastasis to lung/bone.
STAGING: based on involvement of renal vein invasion (IVC/hematogenous spread).
|Urothelial Carcinoma||MNEMONIC: Problems in your Pee SAC: Phenacetin, Smoking, Aniline dyes, Cyclophosphamide. |
Genetics: P53, RB, Lynch Syndrome.
TYPES: Transitional Cell Carcinoma = most common tumor of urinary tract (renal calyces, pelvis, ureters, bladder), painless hematuria.
RISKS: Schistosoma haematobium infection (Middle East), chronic cystitis, smoking, chronic nephrolithiasis. Presents with painless hematuria.
CLINICAL: Hematuria, Palpable Hydronephrosis/flank pain, Bilharziasis, Proximal Urethra, Bad Prognosis.
|Wilms Tumor||GENERAL: most common renal malignancy in children 2-4 (90% sporadic). GENETICS: Loss of function mutations of tumor supressors. |
TYPES: WT1 = WAGR Complex (Wilms, Aniridia, Genitourinary malformation, mentar retadation)-11p13 del; Denys-Drash Syndrome (90% risk for Wilms). WT2 = Beckwith-Wieldemann Syn (Wilms, Macroglossia, Organomegaly (tongue), Muscular Hemihypertrophy).
CLINICAL: Large, palpable unilateral flank mass and/or hematuria, HTN (renin).
HISTO: blastema, primative glomeruli, tubules, and stromal cells. Blastema: blue cells. Triphasic Combination. Anaplasia determines prognosis
Renal Cancer Drugs
|All nibs||→ inhibit PDGFR/VEGF and cause Hand-foot syndrome, also called Palmar-Plantar Erythrodysesthesia.|
|What is Hand-foot syndrome? What is it a SE for?||Side effect of some types of chemotherapy. Hand-foot syndrome causes redness, swelling, and pain on the palms of the hands and/or the soles of the feet.|
|Sunittinib||MOA: Multi-kinase inhibitor - inhibits angiogenesis/prolif (PDGFR/VEGF ). |
SE: neutropenia; thrombocytopenia; hypertension; diarrhea; hyperamylasemia; hand-foot syndrome (palmar-plantar erythrodysesthesia).
|Sorafenib||MOA: Multi-kinase inhibitor - inhibits angiogenesis/prolif (PDGFR/VEGF ). |
SE: rash; diarrhea; hand-foot syndrome).
|Pazopanib||MOA: kinase inhbitor (VEGF 1/2/3;PDGF-α/β; c-KIT; FGF-1/3)|
|Axitinib||MOA: newest kinase inhbitor (VEGF 1/2/3;PDGF-α/β; c-KIT).|
|Temsirolimus||MOA: mTOR inhibitor -- downstream inhibits HIF. Esterified precursor of sirolimus. |
SE: Rash; Pain; infection; edema; thrombocytopenia; neutropenia; hyperlipidemia; hyperglycemia.
|Everolimus||MOA: mTOR inhibitor -- downstream inhibits HIF. Esterified precursor of sirolimus. |
SE: Stomatitis; Infections; Fatigue; Asthenia; Cough; Diarrhea.
|Bevacizumab||MOA: VEGF inhibitor - soaks up ligand so it cannot bind VEGFR2 - stops proliferation/angiogenesis. BIG POINT:: only attacks VEGF pathway, not PDGF-beta, but does stil lcompletely block VEGF. |
SE: asthenia, pain, infection.
|IL-2||MOA: activates lymphoid cells→ T-cell growth factor that activates T-cells and natural killer cells. Short half-life. |
SE: fluid retention, inflammation, hypotension, arrythmias.
|IFN-alpha 2a||MOA: antiproliferative effects on RCCs.|
|Why are RCC's resistant to chemo?||MDR p-glycoprotein (ATP-pump). Renal proximal tubules and renal cell carcinoma express high levels of the MDR protein→ Generally < 10% success rate|
|Temsirolimus works by binding to FKBP12 and subsequently inhibiting what protein(s)?||mTOR|
|Stage IV RCC is aggressively treated with agents such as sunitib, sorafenib, and bevacizumab that ultimately target what aspect of the disease?||Angiogenesis and proliferation|
|Historically, advanced stage renal cell carcinoma has had a bleak prognosis because the disease is resistant to traditional cancer chemotherapeutics (alkylating agents, antimetabolites, and natural products) The primary reason for this resistance is||High expression of the multi-drug resistance pump|
|Can you describe - in a sentence - the difference b/w tacrolimus and everolimus?||Calcenuerin inhibitor vs. mTOR inhibitor|
Transplant Rejection Drugs
|Cyclosporine||Goal: Maintenance. MOA: Block Calcineurin→ blocks T cell activation and apoptosis|
|Tacrolimus||Goal: Maintenance. MOA: Binds FKBP→blocks Calcineurin→ blocks T cell activation and apoptosis.|
|Sirolimus||Goal: Maintenance. MOA: Blocks TOR→permits apoptosis/blocks T cell activation|
|Azathioprine||Goal: Maintenance. MOA: Block DNA synthesis via purine metabolism (BM issues with Allopurinol)|
|Mycophenolate mofetil||Goal: Maintenance. Block DNA synthesis by blocking IMPDH|
|Prednisone||Goal: Induction , Maintenance, & Anti-Rejection. MOA: Blocks Cytokine Expression; Prevent all phases of T cell activation|
|Basiliximab||Goal: Induction. MOA: Blocks IL-2 Receptor→Blocking T cell expansion|
|rATG (Thymoglobulin®)||Goal: Induction. MOA: Destroys Cells via CD3|
|Rituximab||Goal: Anti-Rejection. MOA: Anti-CD20 monoclonal antibody (mouse); Destroys naïve and resting memory B cells|