Oncology, Transplantation Flashcards
The annual age-adjusted cancer incidence rates among men and women are decreasing for all of the ff EXCEPT
melanoma of skin
liver cancer
thyroid cancer
breast cancer
8 essential alterations in cell physiology that dictate malignant growth
- Self-sufficiency of growth signals
- Insensitivity to growth-inhibitory signals
- Evasion of apoptosis
- Potential for limitless replication
- Angiogenesis
- Invasion and metastasis
- Reprogramming of energy metabolism
- Evading immune destruction
Factors that suggest the presence of a hereditary cancer
- Tumor development at a much younger age than usual
- Presence of bilateral disease
- Presence of multiple primary malignancies
- Presentation of a cancer in the lesss affected sex (e.g. male breast cancer)
- Clustering of the same cancer type in relatives
- Occurrence of cancer in association with other conditions such as mental retardation or pathognomonic skin lesions
Benign extracolonic manifestation of FAP
Congenital hypertrophy of retinal poigment epithelium
Epidermoid cysts
Osteomas
Malignant associations of FAP
Duodenal cancer Periampullary cancer Hepatoblastoma Pancreatic cancer Cholangiocarcionama Thyroid ca Desmoid tumor Medulloblastoma
Mutation in RET gene
MEN2 syndrome
Mutation of TP53
Li-Fraumeni syndrome
Mutation in p16
Melanoma
Pancreaitc CA
Esophageal CA
Risk factors for breast cancer
Age at menarche
Ate at first live birth
First degree relative with cancer
Breast biopsies
Routine cancer screening is recommended for
Thyroid Testicles Ovaraies Lymph nodes Oral cavity Skin
Remarks on FAP
CELECOXIB has been shown to reduce polyp number and polyp burden
Remarks on head and neck cancer
13-cis-retinoic acid has been shown both to reverse oral leukoplakia and to reduce second primary tumor dev’t
Hyperacute rejection is caused by
Preformed antibodies
MOA of azathioprine
Converted to 6 mercaptopurine and inhibits both the de novo purine synthesis and salvage purine synthesis
relegated to adjunct after the introduction of cyclosporine and mycophenolate mofetil for transplant recepients
AZA is preferred in recepients who are considering conceiving a child
Drug interactions of azathioprine
Allopurinol, which blocks AZA’s metabolism, increasing the risk of pancytopenia.
If unavoidable, decrease the dose of AZA by 75%
Side effects of cyclosporine
Hypertension Nephrotoxicity Hirsutism Neurotoxicity (tremor, headache, seizure) Gingival hyperplasia Hypomagnesemmia Hyperkalemia
Postrenal transplant graft thrombosis usually occurs within
2-3 days
*doppler ultrasound may help confirm diagnosis
The 1-year graft survival after renal transplantation is
92% - deceased donor kidney
96.5% - living donor kidney
After compoletion of the vascular anastomoses, drainage of a transplanted pancreas is accomplished by anastomosis
Of the duodenal segment to the bladder (bladder drainage)
Or to the small bowel (enteric drainage)
^pancreatic secretions
*for the venous drainage, systemic venous drainage is preferred over portal venous drainage
Contraindications to a liver transplant
Insufficient cardiopulmonary reserve Uncontrolled malignancy or infection Refractory medical noncompliance Severe COPD with O2 dependence Severe refractory pulmonary hypertension with a mean pulmonary artery perssure >35mmHg
Heart donors and recipiens are matchd via
Status on the UNOS waiting list
Size match
Blood type
Heart is assessed if it can withstand up to ___ hours of cold ischemic time during procurement, transport, and surgery
4
Most common mechanism for transplant rejection
Cellular rejection, in which damage is done by activated T lymphocyts
In thre prevention of graft rejection, cyclosporine…
Selectively inhibits T cell activation.
Cyclosporine binds with its cytoplasmic receptor protein, CYCLOPHILIN, which subsequently inhibits the activity of CALCINEURIN, thereby decreasing the expression of several critical T-CELL ACTIVATION GENES, the most important being for IL-2. As a result, t-cell activation is suppressed
Remarks on kidney transplant and death
30-42% of deaths with a functioning kidney graft are due to CVD
The best method of monitoring the development of acute rejection in a patient after cardiac transplantation is
Endomyocardial biopsy
Both T-cell mediated and B-cell mediated rejection are monitored
First organ to be transplanted from living donors
Kidney
The most common organ donated
Kidney
Remarks on kidney transplant
The donor’s left kidney is usually preferable because of the long vascular pedicle. ⭐️
Donor kidneys with multiple renal arteries should be avoided to decreases the COMPLEXITY of the vascular reconstruction and to hel avoid GRAFT THROMBOSIS
Risk of death with donation
Nephrectomy: <0.05%
Partial hepatectomy: 0.2%
The single most important factor in determining whether to perform a transplant between a specific donor and recipient is
ABO blood types of the donor and recipent ✅
The most common diagnosis leading to a heart transplant is
Ischemic dilated cardiomyopathy
Followed by idiopathic dilated myopathy and congenital heart disease
The most significant side effect of sirolimus is
Hypertriglyceridemia, a condition that may be resistant to statins and fibrates
Most common type of rejectiotn
Acute rejection
Occurs within days to weeks
Divided into cellular and humoral rejection
Most common side effect of MMF
GI in nature, diarrhea, nausea, dyspepsia, bloating
Backbone of most immunosuppressive regimens
Calcineurin inhibitor tacrolimus (Prograf)
-acts by binding PKBPs, causing roughly 10-100x more potent inhibition of IL-2 production than cyclosporine (which acts by binding cyclophilins)
*tracrolimus causes a higher incidnece of new-onset diabetes posttransplant than does cylcosporine
Other s/e: alopecia, nephrotoxicity, neurotoxicity, hypertension, hyperK, hypoMg, increased incidence of certain types of INFECTION
