Renal Tumors Ch 15 Aua Review And Weider's

Front 1

In 2006, what were the rates of GU cancer in men?

Back 1

* In adult men, GU cancers accounted for more than 40% of all cancer diagnoses and 15%of all cancer
deaths.

• #1 Prostate cancer (33%)
* Lifetime probability of diagnosis 1 in 6.
* Accounts for 9% of all cancer deaths in men.
* Approximately 12% (27,000 deaths/year) of the 234,000 cases diagnosed each year.

• #4 Bladder cancer (6%)
* Lifetime probability of diagnosis 1 in 28.
* Accounts for 3%of all cancer deaths in men.
* Approximately 21% (13,000 deaths/year) of the 61,000 cases diagnosed each year.

• #6 Kidney cancer (3%)
* Lifetime probability of diagnosis 1 in 61.
* Accounts for 3% of all cancer deaths in men.

• Testicular cancer
* Approximately 4% (370 deaths/year) of the 8,300 cases diagnosed each year.

Front 2

In 2006, what were the rates of GU cancer in women?

Back 2

* In adult women, GU cancer accounted for approximately 3% of all cancer diagnoses.

• #9 Bladder cancer (2%)
* Lifetime probability of diagnosis 1 in 88.
* Approximately 21% (13,000 deaths/year) of the 61,000 cases diagnosed each year.

• #10 Kidney cancer (1%)
* Lifetime probability of diagnosis 1 in 103.
* Approximately 33% (13,000 deaths/year) of the 39,000 cases diagnosed each year (excluding renal
pelvic cancers)

Front 3

Other epidemiology of renal cell cancer

Back 3

• Male to female ratio for malignant renal parenchymal lesions is approximately 1.7 to 1.
• Primarily a disease of the elderly with peak incidence in the 6th and 7th decades of life.
• 10%–20% higher incidence in African Americans for unknown reasons.
• 96% of cases are sporadic, while 4% are associated with familial syndromes.
• The incidence of kidney cancer has increased by a rate of approximately 2%–4% per year over the last 3
decades. This may be explained by:
* Increased incidental detection.
* Unidentified environmental influences.
• There has been a steady rise in the reported mortality rates attributed to kidney cancer over the last 3 decades.
• A slow stage migration has occurred with kidney cancer over the last 3 decades. Current rates of stage at the time of presentation are:
* Localized disease – 53%
* Regionally advanced disease – 20%
*Metastatic disease – 22%
• The only generally accepted environmental risk factor is tobacco exposure:
* Increases relative risk by 1.4 to 2.5.
* All forms of tobacco have been implicated.
* Risk increases with cumulative exposure.

Front 4

What are risk factors for RCC?

Back 4

1. Tobacco
2. Obesity
3. Hypertension
4. Horseshoe kidney
5. Acquired cystic renal disease from chronic renal failure
6. Genetic risks (VHL, BHD< TS, ADPKD)

Front 5

Differential Diagnosis for benign renal tumors

Back 5

RenalCapsular Tumors
- Fibroma
- Leoimyoma
- Lipoma

Renal Parenchymal Tumors
- Oncocytoma
- Adenoma
- Cystic nephroma

Vascular Tumors
- Hemangiomas
- Hamartoma
- Lymphangioma
- Renal artery aneurysm
- AVmalformation

Pseudotumors
- Hypertrophic column of Bertin

Mesenchymal Tumors
- Leiomyoma
- Reninoma (JGtumor)
- Metanephric adenoma angiomyolipoma

Front 6

Differential Diagnosis for malignant renal tumors

Back 6

Tumors of the Renal Pelvis andUreter
- Papilloma
- Urothelial carcinoma
- Squamous carcinoma
- Adenocarcinoma

Renal Parenchymal Tumors
- Conventional carcinoma (clear cell)
- Papillary carcinoma
- Chomophobe carcinoma
- Collecting duct carcinoma

Renal Sarcomas
- Leiomyosarcoma
- Liposarcoma
- Angiosarcoma
- Hemangiopericytoma
- Malignant fibrous histocytoma
- Rhabdosarcoma

Other Renal Tumors
- Carcinoid
- Lymphoma/leukemia
- Metastases
- Wilms’ Tumor

Front 7

Differential Diagnosis for inflammatory renal tumors

Back 7

Abscess
Focal pyelonephritis
Xanthogranulomatous pyelonephritis
Tuberculosis

Front 8

Clues for the Differential Diagnosis of the Radiographic Renal Mass

Back 8

1. Fever, flank pain, pyuria think inflammatory (pyelonephritis or abscess)
2. “Problematic stones”—think of XGP
3. Spontaneous RP bleed—think of underlying RCC
4. SpeckledCa++—think of possible RCC
5. Look for fat by MRI,US orCT and consider AML, liposarcoma
6. For upper pole renal lesions always look for the adrenal
7. Always assess perirenal soft tissues
8. For calcified rounded hilar lesion—think about a renal artery aneurysm
9. Cystic lesions in middle-aged female—think of cystic nephromas

Front 9

What is the classic triad for renal mass presentation? How often does it occur? What does it signify?

Back 9

- Flank mass, hematuria, and pain
- Used to occur in 10% of pts but is now rare because tumors are detected incidentally.
- Triad signifies advanced disease

Front 10

What are characteristics of paraneoplastic syndrome associated with RCC? How often does it occur? Is it reversible? What does it mean if it persists?

Back 10

1. Elevated ESR
2. Weight loss
3. Fever
4. Anemia
5. Hypertension (from increased renin)
6. Hypercalcemia (from release of PTH-like substance)
7. Stauffer's synderom (hepatic dysfunction that is reversible hepatitis)
8. Elevated alk phos
9. Polycythemia (from increased erythropoietin)
- Occurs in 20-30% of pts with RCC.
- Syndrome is reversible with tumor resection
- If it persists, metastatic disease is probably present and prognosis is poor

Front 11

What are labs/imaging ordered on initial work-up?

Back 11

- CT/MRI, chest x-ray, BMP, alk phos, LFTs, serum calcium, CBC, and urinalysis.
- Obtain chest CT if pts has pulm symptoms.
- Obtain bone scan if pt has bone pain, elev alk phos, elev calcium

Front 12

How do you begin clinical staging?

Back 12

1. Clinical staging for RCC begins with a thorough history, physical exam and judicious use of laboratory
tests
2. Symptomatic presentation, significant weight loss (>10% of total body weight), bone pain and poor
performance status all suggest advanced disease as do a physical exam findings of a palpable mass or
lymphadenopathy.
3. Nonreducing varicocele or lower extremity edema suggests possible venous involvement.
4. Absence of findings on history and physical exam does not rule out advanced disease.
*Abnormal liver function tests, elevated alkaline phosphatase, sedimentation rate or anemia
suggest possible advanced disease.
* Clinical clues will often be helpful in distinguishing amalignant renalmass fromother
causes

Front 13

How do you begin radiographic staging?

Back 13

1. Radiographic staging of RCC requires a contrast based study demonstrating enhancement (blood flow)
of the mass
2. 3-phase CT of the abdomen and pelvis, with all 3 phases being done at the same setting is imperative.
3. This is the single best test. Should not rely on a noncontrast CT or a contrast CT performed at
different settings, especially on different machines.
4. Enhancement (>15–20 units by CT) of the
mass is required.

Front 14

When should MRI be performed?

Back 14

1. MRI pre- and post gadolinium should be reserved for patients with suspected venous involvement, those with a iodine contrast allergy and those with renal insufficiency.
2. Patients with lymphadenopathy >2 cm generally harbor malignancy. Smaller nodes may be inflammatory.
3. Venous involvement is best imaged by MRI. The sensitivity of CT for renal vein and IVC involvement
is 78%–96%. Venography is reserved for patients with equivocal MRI findings or those with contraindications to MRI.
4. Transesophageal echo is an accuratemethod of determining the cephalad extent of the tumor and
may be used intraoperatively. It has no real advantage over MRI in the preoperative setting.

Front 15

What are the indications for renal biopsy?

Back 15

1. Appropriate for pts in whom a wide range of management options are under consideration
2. Biopsies should be considered in patients with suspected lymphoma, abscess/infectious or metastatic diseaseto the kidney. In most cases of patients with a primary malignancy elsewhere, metastases to the kidney are late and are usually accompanied by extensive disease elsewhere. Solitary renal metastases
are uncommon.
3. Risk stratification tools including the risk of RCC (vs a benign lesion) and grade can be calculated using published nomograms (www.cancernomograms.com).

Front 16

What are reasons not to obtain biopsies?

Back 16

- Is non-diagnostic 10-15% of the time
- Most primary solid renal masses are malignant
- False negative occur in 1-2%
- Tumor spillage with cystic masses
- Risk of hematoma, spillage, infection, and pseudoanuerysm

Front 17

What are secondary renal masses that are mets from most common to least common?

Back 17

Lymphoma, lung, and breast

Front 18

What should be included as part of the metastatic evaluation?

Back 18

1. All cases should include a routine chest x-ray, careful review of the CT findings of the abdomen and pelvis, and liver function tests.
2. Bone scan, CNS imaging, and chest CT can all be reserved for symptomatic patients, abnormalities
on CXR, abdominal imaging or laboratory studies (ie, elevated alkaline phosphatase), or
patients with extensive disease identified by routine studies.
3. PET has shown poor sensitivity for routine use in the evaluation of RCC. Newer immunoPET scans like the G250 scan may be available soon and are specific for clear cell RCC

Front 19

What can you see on ultrasound of a lesion?

Back 19

1. A simple cyst on US should be anechoic, have good through transmission and posterior wall enhancement.
2. Complex or hyperdense cysts on US may appear to be solid lesions and read incorrectly as RCC.
3. Fatty lesions such as an angiomyolipoma (AML) appear hyperechoic (white) on US.

Front 20

What can you see on MRI of a lesion?

Back 20

1. A simple cyst on MRI will appear bright on T2 and dark on T1. It will not enhance. A hyperdense cyst may appear bright on T1 and dark on T2, depending on the age and composition of its contents. It will not enhance.
2. Fat (ie, froman AML) is generally bright on MRI but depends on technique. Look at subcutaneous fat for an idea as to how the fat looks on that particular MRI sequence.

Front 21

What are pseudotumors? How do you differentiate pseudotumors from true tumors?

Back 21

1. Solid renal masses on radiographic studies that are actually normal renal parenchyma. Examples include column of Bertin, fetal lobation, dromedary hump, hilar lip or uncus, and nodular compensatory hypertrophy
2. obtain a DMSA renal scan; true tumors show decreased isotope uptake

Front 22

What types of solid renal masses are there and what are their relative frequencies?

Back 22

- Clear cell RCC 65%
- Papillary RCC 10-15%
- Chromophobe RCC 5-10%
- Collecting duct carcinoma <1%
- Oncocytoma 7%
- AML 1-2%

Front 23

Name 7 hereditary syndromes.

Back 23

1. Hereditary clear cell RCC
2. Hereditary papillary RCC
3. Familial oncocytoma
4. Von hippel lindau
5. Birt-Hogg Dube
6. Tuberous sclerosis
7. Hereditary Leiomyoma RCC

Front 24

What are skin lesions associated with RCC?

Back 24

- Adenoma sebaceum: Pink or red colored papules overlying cheek bones or nasolabial folds
- Ash-leaf spots: hypopigmented macules on trunk or buttocks
- Shagreen patches: orange-peel textured plaques on lower back
- Periungual fibromas: flesh-colored papules near the nail bed
- Fibrofolliculomas - small white or flesh-colored papules on the face, neck, back or upper trunk

Front 25

Where is the VHL gene (clear cell RCC) located?

Back 25

3p25

Front 26

Where is the Type 1 Papillary RCC) located?

Back 26

7q31

Front 27

Where is the gene for Type 2 Papillary RCC - Hereditary Leiomyoma RCC?

Back 27

1q42

Front 28

Where are the tuberous sclerosis genes located?

Back 28

1. 9q42 - TSC1
2. 16p13 - TSC2

Front 29

Where is the Birt Hogg Dube gene located?

Back 29

17p11

Front 30

What 3 syndromes have cutaneous manifestations? Which are painful and which are painless?

Back 30

1. BHD has painless fibrofollicumomas on head and neck
2. Tuberous sclerosis has painless adenoma sebaceum on cheeks and nose
3. Hereditary leiomyoma RCC has painful leiomyomas that can occur anywhere on the body

Front 31

What is the classic triad of tuberous sclerosis?

Back 31

Mental retardation, seizures, and adenoma sebaceum. Only seen in 30% of cases

Front 32

What genes are associated with tuberous sclerosis? Is is autosomal dominant or recessive?

Back 32

*TSC1 gene is on chromosome 9q34.
*TSC2 gene is on chromosome 16p13.
*They are AD
*Defects in TSC genes have not been directly linked to cases of RCC

Front 33

What are the characteristics of tuberous sclerosis?

Back 33

Hamartomas of the retina, brain (cerebral cortex tubers), kidney (AML), lung (lymphangioleiomyomatosis), and heart (cardiac rhabdomyomas)

Front 34

What are renal manifestations associated with tuberous sclerosis

Back 34

- AML in 60% of pts. These can be multiple and bilateral
- RCC in 2% of pts
- Renal cysts usually develop in childhood

Front 35

What gene is associated with Birt-Hogg Dube? Is is autosomal dominant or recessive?

Back 35

BHD gene is on chromosome 17p11. It is AD

Front 36

What are the characteristics of Birt Hogg Dube?

Back 36

- Skin fibrofolliculomas: usually painless and appear after age 30
- Air filled pulmonary cysts
- Spontaneous pneumothorax
- Renal tumors: multifocal and bilateral
* Most commonly oncocytoma and chromophobe carcinoma
* Clear cell and papillary tumors can coexist
- Other possible associations include nevi, parathyroid adenomas, lipomas, oral mucosal papules, colonic polyps or tumors.

Front 37

What are fibrofilliculomas?

Back 37

benign, painless, small white or flesh-colored papules on the face, neck, back, or upper trunk that usually appear after age 20-30

Front 38

What are renal manifestations associated with Birt Hogg Dube?

Back 38

- 25% of pts with BHD develop renal tumors, most bilateral and multiple
- Most common types of tumors are clear cell RCC, chromophobe RCC, and oncocytoma

Front 39

What gene is associated with Von Hippel Lindau? Is is autosomal dominant or recessive?

Back 39

VHL gene encodes the VHL protein. It is AD and is caused by a mutation of VHL gene. VHL is a tumor suppressor gene

Front 40

What are the non-urologic characteristics of von Hippel Lindau?

Back 40

1. Cerebellar hamangioblastomas
2. Spinal hemangioblastomas
3. Retinal angiomas
4. Pancreatic cysts and islet tumors

Front 41

What are the urologic characteristics of von Hippel Lindau?

Back 41

1. Renal cysts (75%)
2. Clear cell RCC (50%)
3. Pheochromocytomas (15%): Most frequently associated with missense mutations of the VHL gene that encode for an amino acid substitution
4. Epididymal cystadenomas(10%)
5. Epididymal cysts (7%)

Front 42

How does the VHL gene work?

Back 42

The VHL protein is regulated by HIF. If VHL protein is mutated, HIF cannot bind and it will accumulate in the cell. This will lead to upregulation of VEGF, PDGF, and other proteins which regulate cellular growth and development

Front 43

How do tumor suppressor genes work?

Back 43

They negatively regulate growth. Their function is to prevent uncontrolled proliferative processes including cell division. Knudsen's two hit hypothesis predicts that it only takes one functioning copy to regulate growth, therefore both copies or alleles must be mutated or silenced in order to promote carcinogenesis.

In the case of a germ line mutation, the offspring inherits a mutated copy of the tumor suppressor from one of their parents. In this scenario,
only the second copy of the gene need undergo somatic mutation to induce transformation.
This is the case with inherited forms of clear cell kidney cancer associated with the VHL syndrome.

In cases of sporadic clear cell carcinoma, the patient is born with 2 normal copies of the VHL gene, both of which need undergo a somatic mutation to induce transformation. Since this is a statistically less common event, clear cell RCC is less frequent in nonmutant VHL carriers.

Front 44

What are the established genetic mechanisms are responsible for the majority of known mutations in tumor suppressors?

Back 44

1. Loss of heterozygosity (LOH)
2. Point mutations
3. Promoter hypermethylation

Front 45

What is Loss of heterozygosity (LOH)?

Back 45

* Involves the loss of specific chromosomal regions that contain known or presumptive tumor suppressor genes. LOH may be achieved due to a deletion, gene conversion, mitotic recombination, translocation, chromosome breakage and loss, chromosomal
fusion or telomeric end-to-end fusions, or whole chromosome loss. This may result in asymmetric loss of a gene or homozygous deletions, whereby both copies of the gene are affected.
* LOH is a useful diagnostic marker because of its high level of specificity for transformed cells.

Front 46

What is a point mutation?

Back 46

Occur at the level of individual nucleotides where substitutions, insertions and deletions may result in frameshift, missense and nonsense mRNA transcripts and ultimately truncated or nonfunctional proteins.

Front 47

What is a promoter hypermethylation?

Back 47

In most somatic cells, the CpG dinucleotide islands in the controlling or promoter region of a gene are normally protected from methylation. Although not a distinct genetic event, promoter hypermethylation is an epigenetic event capable of silencing expression.

Front 48

What type of RCC is related to von Hippel Lindau? How common is it in VHL? At what age do they develop?

Back 48

- Clear cell RCC?
- Occurs in 50% of pts with VHL
- Develops at age 20-40

Front 49

How do you treat patients with VHL?

Back 49

1. NSS for patients with VHL represents an absolute indication.
2. Adequate surgical treatment requires excision of all solid and cystic renal lesions.
3. Unfortunately, patients with VHL have multifocal disease which can rarely be excised fully without radical nephrectomy. Several studies demonstrate a 3-cm threshold to intervene in patients with VHL. In these patients, lesions >3 cm have been shown to have a greater propensity toward the development of metastases, although there have been reports of smaller lesions associated with metastases. Therefore,
NSS may be withheld until the dominant lesion reaches 3 cm. Surgery should then be aimed at resetting the biological clock, such that all dominant lesions are excised and the renal remnant is watched closely until a dominant lesion reaches 3 cm.
4. Options in this setting include radical nephrectomy with transplantation, attempted NSS or ablative technologies
5. When extensive bilateral RCC is present and renal sparing surgery is not possible, bilateral nephrectomy and dialysis is required

Front 50

What part of the collecting system do papillary adenomas develop? Are these benign or malignant? How big are these lesions?

Back 50

- Arise from the proximal tubule and have similar cytogenetic abnormalities as papillary RCC
- These lesions are benign
- They lesions are <5mm

Front 51

What part of the collecting system do oncocytomas develop? What is the typical finding of oncocytomas on imaging? How do you treat oncocytomas? What % of solid renal masses does it represent?

Back 51

- Distal convoluted tubule
- Spoke wheel pattern of tumor arterioles with a lucent rim around the tumor is often seen on arteriography, but this can occur with RCC
- Surgical excision is treatment of choice because imaging cannot distinguish between RCC and oncocytoma.
- Represents 3-7% of all solid renal masses
- May be part of the Birt-Hogg-Dubé syndrome and be part of the spectrumof chromophobe carcinoma continuum.
- Occurs inmiddle-aged patients with a slightmale preponderance

Front 52

What do oncocytomas look like on gross pathology? On microscopic pathology? On electron microscopy?

Back 52

- Mahogany or tan mass with a fibrous capsule and often with a centra scar.
- Under microscope, nests of granular eosinophilic cytoplasm
- On electron microscopy, the cytoplasm is packed with mitochondria

Front 53

What is an AML and how does AML present? What size are AMLs likely to hemorrhage?

Back 53

- AML is a benign renal mass composed of blood vessels, smooth muscle, and fat
- Presents in females age 40-60, rare before puberty
- Presents in 60% of pts with tuberous sclerosis (but most pts with AML do not have tuberous sclerosis - only 20-30%)
- AML is often asymptomatic but symptoms include flank pain, hematuria, and hemorrhage with hypotension (Wunderlich's syndrome)
- Pregnancy increases risk of hemorrhage
- AMLs >/= to 4cm are more likely to by symptomatic and hemorrhage

Front 54

What is the syndrome called after retroperitoneal hemorrhage with AML? what increases the risk of spontaneous hemorrhage in AML?

Back 54

- Wunderlich's syndrome
- Pregnancy increases the risk of spontaneous hemorrhage with AML

Front 55

What are the imaging characteristics of AML? How do you diagnose AML?

Back 55

- AML rarely contain calcification. If calcium is present, the mass is likely RCC
- The amount of fat in an AML varies and in 14%theremay be no fat
- Classic CT scan findings: HU of -20 to -80 on noncontrast indicating fat content, homogenous, not calcified, and not cystic
- On ultrasound, AML is hyperechoic
- It is the only primary renal tumor that expresses HMB-45

Front 56

How do you treat AML?

Back 56

- Observation with yearly ultrasound is recommended for AML that is asymptomatic and <4cm
- For asymptomatic AML >/= 4cm, tx with arterial embolization or partial nx
- For stable pts with hemorrhage, arterial embolization can be performed but may require repeat tx
- For unstable pts with hemorrhage, immediate surgical exploration should be performed

Front 57

Where is the gene for Type 1 papillary RCC? What type of gene is it? What does it encode?

Back 57

- It is on chromosome 7q31
- Oncogene
- c-Met gene encodes met protein which is a receptor tyrosine kinase family

Front 58

What is an oncogene?

Back 58

It is responsible for gain of function events leading to cellular growth, differentiation or proliferation through the accumulation of normal signaling proteins or creation of a mutant activating protein.

Unlike tumor suppressor genes, oncogenes may only require a single mutating event in one (not both) allele to promote malignant transformation.

The most common mutating genetic event is point mutation.

Front 59

What syndrome is associated with Type 1 papillary RCC? How does it manifest?

Back 59

- Hereditary Papillary RCC
- There are no extrarenal manifestations
- The rarest form of hereditary RCC
- Characterized by bilateral and multifocal type I Papillary RCC

Front 60

Where is the gene for Type 2 papillary RCC? What type of gene is it? What does it encode?

Back 60

- It is on chromosome 1q42
- It is a tumor suppressor gene
- It encodes the Kreb's cycle protein fumurate hydratase
- More aggressive type of papillary RCC

Front 61

What syndrome is related to Type 2 Papillary RCC? How does it manifest?

Back 61

- Hereditary leiomyoma RCC
- Painful cutaneous leoimyomas which can occur anywhere on the body
- Uterine fibroids: early age of onset, multiple, painful
- Type 2 papillary RCC - very aggressive tumors

Front 62

What is the most common type of RCC? What are microscopic features and why? What part of the collecting system does it arise from? What chromosome abnormalities is it associated with?

Back 62

- Clear cell RCC: accounts for 70-80% of all RCC
- Demonstrates low nuclear/cytoplasm ration adn has a clear cytoplasm
- They cytoplasm is filled with glyocen and lips with dissolve during tissue processing resulting in a clear cytoplasm
- Arises from the proximal tubule
- Associated with the loss of 3p
- Associated with VHL, BHD, TS, and hereditary clear cell RCC
- Moderate malignant potential
- 2-5% contain sarcomatoid features
- More likely to respond to immuno and targeted therapies

Front 63

Where can you find sarcomatiod features of RCC? What does presence of this mean to prognosis?

Back 63

- Sarcomatoid elements can be present in any tumor type
- Poorly differentiated regions of other histological types.
- Found in 1%–5%of RCCs, most commonly with conventional or chromophobe RCC.
- Median survival is poor (depending on stage).
- Presence indicates high grade tumor and worse prognosis

Front 64

What part of the collecting system does Chromophobe RCC arise? What are its microscopic characteristics? What disease is it associated with? What is its malignant potential? Are there any cytogenetics associated?

Back 64

- Arises from the collecting duct or distal tubule
- Granular eosinophilic cells often with perinuclear halo, and pale transparent cells
- Positive Hale's colloidal iron stain, distinct cell borders, and perinuclear halo. On electron microscope, microvesicles fill the cytoplasm
- BHD
- Low malignant potential
- Multiple chromosome deletions
- Account for 5% of all RCC

Front 65

What is oncocytoma similar to microscopically and how can you differentiate between Chromophobe RCC and oncocytomas?

Back 65

- Both have similar microscopic appearance
- Only the border of oncocytomas stain blue with Hale's colloidal iron (negative stain) whereas the entire cytoplasm of chromophobe RCC will stain blue (positive stain).
- There are microvesicles in cytoplasm of chromophobe whereas oncocytomas have mitochondria filled cytoplasm

Front 66

What is another name for Chromophilic RCC? What are microscopic features and how many types are there? What part of the collecting system does it arise from? What chromosome abnormalities is it associated with? What is the syndrome related to this type of RCC?

Back 66

- Secondmost common histological type, representing 10%–15%of all RCCs
- Also known as Papillary RCC, now more common
- Characteristic pathologic feature is the papillary architecture
- There are 2 subtypes
- Type 1 have a basophilic cytoplasm and are usually low grade
- Type 2 have an eosinophilic cytoplasm and are usually high grade with a worse prognosis
- Papillary RCC arises from the proximal tubule and is associated with c-met gene mutaion on chromosome 7 and loss of Y chromosome
- Herediatry papillary RCC is the familial form/syndrome
- Tends to be multicentric in as many as 40%of cases.
- Grade for grade and stage for stage, prognosis is likely not any different than with conventional
RCC.

Front 67

What is the most common type of RCC found in pts with acquired cystic renal disease from chronic renal failure?

Back 67

- Papillary RCC; therefore it is the most common type found in pts on dialysis

Front 68

What is another name for Bellini duct carcinoma? What are microscopic features? What part of the collecting system does it arise from? What is the prognosis?

Back 68

- Collecting duct carcinoma
- Microscopic appearance demonstrate hob nail cells lining the tubular spaces and pronounced stromal desmoplasia
- Arises from medullary collecting duct or duct of Bellini. Usually located in the renal medulla or papilla
- It is a rare, highly malignant cancer. 40% present with mets. 5-year survival is rare
- May occur in younger population
- Immunohistochemical and molecular analysis suggest that these tumors resemble urothelial
carcinomas.
* Systemic treatment often includes bladder like chemotherapy regimens

Front 69

What type of patients do renal medullary carcinomas arise in? What part of the collecting system does it arise from? What is the prognosis?

Back 69

- Primarily occurs in African American adults with sickle cell trait typical age 10-39.
- Arises from collecting duct
- Mean survival time from surgery is approx 15 weeks. It is rare, rarely confined to kidney, rarely responds to chemo or radiation, and only renal tumor with racial predilection
- Typically diagnosed in the 3rd decade of life.
- Most cases are locally advanced and metastatic at diagnosis.
- Highly aggressive. Mean survival is 12–15 months.

Front 70

What are clinical features that affect prognosis?

Back 70

1. performance status,
2. presence of symptoms related to primary ormetastases,
3. weight loss.
4. Also included are possible laboratory factors such as anemia, polycythemia, thrombocytosis, hypercalcemia and/or elevated alkaline phosphatase (MSKCC criteria).

Front 71

What are anatomic factors that affect prognosis?

Back 71

1. tumor size,
2. extension,
3. adrenal, venous or lymphatic involvement
4. radiographically identifiable metastatic disease

Front 72

What are histologic factors that affect prognosis?

Back 72

1. histologic type,
2. nuclear grade,
3. presence of necrosis,
4. sarcomatoid features
5. invasion of the collecting system.

Front 73

What are the most important prognostic factors?

Back 73

1. stage,
2. grade,
3. histology,
4. symptoms at presentation
5. performance status

Front 74

What are the 5-year risks of recurrence for local or regional RCC fully excised?

Back 74

* 5%–9%for low-risk disease.
* 20%–25%for intermediate-risk disease.
* 60%–80%for high-risk disease.

Front 75

What percent of patients present with metastatic RCC? Whats is a risk factor? What are the risk of mets based on size? Are mets usually singe or multiple?

Back 75

- 25%
- Size; larger primary turmors have a higher risk of mets at presentation
- </= 3cm is 4% risk
- 3-7cm is 7-16% risk
- 7-10cm is 30% risk
- >10cm is 43% risk
- Mets are usually multiple

Front 76

How do mets spread? What are the rates of distant and regional mets?

Back 76

-Lymphatic and hematogenous spread with equal frequency
- Distant mets are present 50% of pts with regional lymph node mets

Front 77

How are mets identified?

Back 77

1. Most metastases (50%–75%) are asymptomatic.
2. More than 70% of metastases are identified by abdominal imaging and CXR.

Front 78

What are the most common sites of recurrence?

Back 78

lung>bone>liver>adrenal>contralateral kidney>CNS
Site and median time to recur:
Lung (38%) 1.6
Bone (18%) 1.5 -The most common site of bone met is to the spine
Liver (13%) 1.7
Local (includes adrenal) 10% 1.7
CNS (8%) 2.5

Front 79

When do recurrences occur?

Back 79

Most recurrences occur within the first 24 months after resection. The risk of recurrence decreases as
disease-free interval increases.

Front 80

When do mets usually occur?

Back 80

- If mets develop after nephrectomy, they usually occur within one year of surgery

Front 81

Grade

Back 81

• Nuclear features can be highly variable in RCC.
• Grading systems are based on nuclear size, shape, and presence or absence of nucleoli.
* Fuhrman’s system is the most common classification for conventional RCC
• Grade 1 and 2 are considered low grade.
• Papillary (chromophilic) RCC are classified as type 1 (low grade, basophilic) or type II (high grade, eosinophilic).
• Tumor grade is recognized as an important prognostic variable in RCC.

Front 82

Stage

Back 82

• Refers to the local, regional and systemic extent of disease.
• Historically used the Robson staging system.
• Currently uses the 2010 v7 AJCC TNM staging system.
• The TNM system defines the anatomic extent of disease explicitly and can be used to facilitate
comparisons of data fromcenters worldwide.
• Changes in the v7 of TNMfor kidney include the addition of T2 substages based on tumor size, changes in the substaging of T3 tumors such that pT3a is for tumors involving the fat or segmental venous branches and pT3b/c depends on height/invasion of IVC involvement and changes in T4 to include ipsilateral adrenal involvement.

Front 83

T1a

Back 83

Tumor 4cm or less limited to kidney

Front 84

T1b

Back 84

Tumor 4-7cm limited to kidney

Front 85

T2a

Back 85

Tumor 7-10cm limited to kidney

Front 86

T2b

Back 86

Tumor more than 10cm limited to kidney

Front 87

T3a

Back 87

Tumor grossly extends into renal vein or its segmental branches, or tumor invades perirenal and/or renal sinus fat but not beyond Gerota's fascia

Front 88

T3b

Back 88

Tumor grossly extends into vena cava below the diaphragm

Front 89

T3c

Back 89

Tumor grossly extends into vena cava above the diaphragm or invades into the wall of vena cava

Front 90

T4

Back 90

Tumor invades beyond Gerota's fascia or into the ipsilateral adrenal gland

Front 91

What are the primary goals of T1 RCC management?

Back 91

1. Save the kidney
2. Performsurgery usingMIS technique if possible
3. Surgery remains themainstay of treatment for RCC. The objective is to resect all tumors with an adequate negative surgical margin.

Front 92

What is the primary treatment modality for RCC?

Back 92

- surgical excision

Front 93

Who should undergo active surveillance for enhancing renal masses in the absence of mets?

Back 93

- AS is a reasonable option for pts with limited life expectancy or for those who are unfit for or do not desire intervention

Front 94

For a </= 3cm enhancing renal mass, what are the chances of it being benign, high grade, extending locally outside kidney, or have node/distant mets?

Back 94

- 20% benign,
- 12% high grade,
- 6% extending locally outside kidney,
- <4% present with node/distant mets?

Front 95

What is the risk of developing mets within 3 years of diagnosis in an untreated pt with an enhancing renal mass </= 3cm?

Back 95

- 1%

Front 96

What did the meta-analysis by Chawla et al in 2007 show regarding surveillance for an enhancing rena mass </= 4cm?

Back 96

It showed a 1% risk of developing mets and an average tumor growth rate of 2-4mm per yeat. Tumors >4cm had a higher risk of tumor growth and mets. This study suggests that in the short term, surveillance for a renal mass </= 4cm has a low risk of mets and local tumor growth but in the long-term, surveillance may compromise survival

Front 97

What did a retrospective study by Zini et al in 2009 show?

Back 97

Exicision improved cancer specific survival by 9.4% at 5 years in pts with an enhancing renal mass </= 4cm. So long term data suggests that even small renal masses should be removed in pts who can tolerate an invasive procedure.

Front 98

What is considered a radical nephrectomy?

Back 98

1. Early ligation of the vessels, removal of kidney outside Gerota's fascia, excision of the ispilateral adrenal and regional lympadenectomy
2. As per a recently completed phase III randomized European Trial (EORTC 30881), resection of clinically negative nodes does not improve PFS or OS. Unsuspected node positivity was identified in only 4% of cN0 patients.
3. Cases of clinically involved lymphadenopathy require resection of all involved nodes where feasible, particularly if there are no metastases

Front 99

Should you always excise the ipsilateral adrenal glank?

Back 99

Excision of the ipsilateral adrenal gland is not routinely necessary in the absence of radiographic
involvement.

Front 100

What are the operative approachs to the kidney and tumor?

Back 100

1. Depends on the size and location of the tumor, as well as the body habitus of the patients.
2. Open approaches include flank (subcostal, intercostals or with excision of portion of the rib), chevron, or thoracoabdominal (especially useful on the right side with large upper pole tumors, IVC involvement or adjacent organ involvement).
3. Laparoscopic approaches include transabdominal, retroperitoneal or hand assisted.

Front 101

What are advantages of lap nephrectomy?

Back 101

1. has emerged as a less morbid and more safe option formost cases of localized RCC, including large tumors (<20 cm), patients with significant prior surgical histories, the morbidly obese and even in cases with early venous involvement.
2. Multiple studies have demonstrated the safety and efficacy of laparoscopic nephrectomy in these settings.

Front 102

What does renal/nephron sparing surgery (NSS) entail?

Back 102

1. Complete local excision of the renal tumors, leaving the largest possible amount of normal functioning parenchyma.
2. Enucleation of the tumor implies incomplete resection and is not a preferred term for nephron-sparing surgeries for localized kidney tumors
3. Interest in NSS has grown as a result of stage migration due to improved imaging, a greater
experience with renovascular surgery, improvements in surgical methods (including means to prevent renal ischemic injury) and excellent long-term published outcomes
4. Large population–based studies suggest that NSS is under utilized nationally

Front 103

What are absolute indications for NSS?

Back 103

bilateral tumors or a tumor in a anatomically or functional solitary kidney/poor renal function

Front 104

What are relative indications for NSS?

Back 104

1. A renal tumor involving kidneys compromised or potentially compromised by systemic disorders, which decrease global renal function (diabetes, hypertension,
glomerulopathy, etc).
2. Elective – an ipsilateral renal tumor in an otherwise healthy individual with 2 anatomically and functionally normal kidneys.
A. The accepted tumor size cutoff for elective partial nephrectomy is 4 cm;
B. However, lesions ≥7 cmmay also be amenable to safe elective partial nephrectomy

Front 105

Why is renal sparing surgery usually limited to a solitary clinical stage T1 tumor?

Back 105

- Partial nx has a higher local recurrence rate of clinical stage T2-T4 (3-6% vs 1% for T1)
- radical nx achieves longer cancer specific survival for tumors >7cm

Front 106

What are options for renal sparing surgery?

Back 106

- Enucleation: no margin of normal renal tissue
- Partial nx: the preferred method of nephron sparing surgery bc long term data proves that it is effective
- Ablation: usually reserved for pts who cannot tolerate surgical excision and who have a small peripheral tumor

Front 107

How much of a margin should be taken with parital nx?

Back 107

Some recommend 1cm margin however the size of a negative margin does not impact prognosis. A close margin achieves the same cure rate as an ample margin; therefore, a close margin should be considered truly negative

Front 108

What are Pre-Op implications of NSS?

Back 108

1. Specific renal imaging such as video 3-dimensional volume-rendered CT may be useful to delineate the relationship of the tumor to the intrarenal vascular supply and collecting system.
2. Additionally, a functional assessment of the contralateral kidney, such as a contrast-based CT orMRI, is imperative.
3. Nuclear renal scan adds little in the absence of a well-done, contrast-based CT/MR.

Front 109

What are Intra-Op implications of NSS?

Back 109

1. Intraoperative considerations should mimic that of a donor nephrectomy with excellent exposure and hemostasis, complete vascular control and promotion of a brisk intraoperative diuresis.
2. Once these factors are assured, hilar clamping (usually independently with separate arterial and venous clamps), full excision with a negativemargin, and detailed reconstruction of the collecting system and renal remnant are essential. Warm ischemic times should be <30minutes and cold ischemic times should be <60 minutes whenever possible. Clamping and reclamping should be avoided and is associated with reperfusion injury.
3. Recent data in 660 partial nephrectomies in solitary kidneys suggests that percent of parenchyma preserved and preoperative GFR are most predictors of postoperative renal function.

Front 110

What is the risk of temporary or permanent dialysis associated with NSS?

Back 110

Patients undergoing NSS for absolute or relative indications, particularly in the case of a solitary kidney, should be told there is a 5%–8% risk of temporary or permanent dialysis associated with NSS.

Front 111

What are considerations for lap vs open parital nx?

Back 111

- Warm ischemia time is usually longer with lap partial nx
- lap partial nx has a higher risk of post-op hemorrhage but transfusion rates are similar
- lap partial nx have a higher risk of being converted to radical nx (3.4% vs 1.6% for open partial nx)

Front 112

What are ways to minimize ischemic renal damage during partial nx?

Back 112

- give mannitol 12.5gm IV 5 and 10minuites prior to clamping the renal artery bc mannitol scavenges free radical and reduces cellular damage
- clamp artery only once. you can consider leaving renal vein unclamped to permit retrograde renal perfusion
- if renal ischemia time is >30min, cool the kidney with an ice path for 15 min after clamping the arter. Cooling the kidney provides up to 3 hours of ischemia time without permanent renal damage
- Avoid hypotension and hypovolemia

Front 113

What is the rate of urinary fistula rate with NSS?

Back 113

1. Urinary fistula rates are 3%–8% depending on the size of the lesion, the location of thelesion, the ischemic time and the experience of the surgeon.
2. Most fistulae will close after a time with adequate drainage. Some may require a ureteral stent and/or Foley catheter to promote healing.

Front 114

What are the rates of complications when comparing radical vs. partial nx?

Back 114

Partial nx has highter rates of complications:
- hemorrhage >1L (3.1% vs 1.2% for radical nx)
- Urine leak/fistula (4.4% vs 0% for radical nx)
- Re-operation for complications (4.4% vs. 2.4% for radical)

Front 115

What is the difference in renal function comparing radical vs. partial nx?

Back 115

- Post-op creatinine is higher after radical nx than partial nx
- Partial nx results in a lower risk of chronic renal insufficeincy defined as creatinine > 2.0 and lower risk of proteinuria

Front 116

What is the difference in survival and recurrence comparing radical vs partial nx?

Back 116

- retrospective studies show that nephron sparing surgery and radical nephrectomy achieve equivalent disease-free survival but local recurrence is higher with partial nx (3% vs 1% in radical nx)
- Overall survival is improved in pts undergoing partial nx due to cardiac protection and preservation of renal function

Front 117

When there are multiple, bilateral tumors, which side should you operate on first?

Back 117

- Perform partial nx on the easy side first so that it has time to recover. Also, the difficult side has a higher likelihood of requiring radical nx.
- Decreases chance of requiring dialysis during recovery period

Front 118

How often do bilateral synchronous sporadic RCC occur?

Back 118

1. 0%–5%of cases and may occur more commonly
in African American men.
2. In the case of bilateral RCC, surgeries are usually staged with the less involved size treated first. This provides more options to the surgeon and may
reduce the need for perioperative dialysis.

Front 119

How often does direct invasion or mets to the adrenal gland occur?

Back 119

- 2-10%

Front 120

How often is adrenal insufficiency after unilateral adrenalectomy?

Back 120

- very rare when the patient has a normal contralateral adrenal gland

Front 121

What factors increase risk of mets from RCC in ipsilateral adrenal gland?

Back 121

- tumor in upper pole of kidney
- local tumor extension through the renal capsule
- tumor thrombus up to level of adrenal vein
- tumor size >7cm
- abnormal ipsilateral adrenal gland on pre-op imaging (ie non-visualization of ipsilateral adrenal gland)
- If none of the above are present, adrenal mets are rare

Front 122

When should you consider removing the ipsilateral adrenal gland?

Back 122

- upper pole tumor >7cm in size
- tumor thrombus up to the level of adrenal vein
- abnormal or non-visualized ipsilateral adrenal galnd on pre-op imaging
- intraop suspicion of adrenal involvement

Front 123

Does lymph node dissection at the time of radical nx change survival or progression? Does it increase surgical complication?

Back 123

- Regional lymph node dissection does not improve cure rate or survival in pts who undergo radical nx for clinical stage N0M0.
- LND does not increase risk of surgical complications

Front 124

How often are mets found in lymph node dissection at the time of radical nx?

Back 124

Regional lymph node mets were found in 4% of pts

Front 125

How often are node mets found in palpably normal nodes and palpably enlarged nodes?

Back 125

- 1% in palpably normal nodes
- 17% in palpably enlarged nodes
- Most palpable nodes do not harbor mets in pts who were clinical stage N0 preoperatively

Front 126

What are risk factors for positive lymph nodes?

Back 126

- Stage T3-T4
- Grade 3-4
- Tumor size >/= 10cm
- Tumor necrosis or sarcomatoid elements

Front 127

For clinical stage N1-2 RCC, does LND improve survival?

Back 127

- Yes. In addition, data suggests that pts who receive post-op IL-2 have a better response when grossly positive nodes are resected

Front 128

When is radical nx recommended?

Back 128

It is always recommended except
- When renal masses <7cm are amenable to partial nx
- Some AMLs
- Bosniak I, II, or IIF renal cysts
- Unresectable tumors

Front 129

What are ablation options?

Back 129

1. Thermal ablative techniques include renal cryosurgery and radiofrequency ablation (RFA).
2. Both can be administered percutaneously or through laparoscopic exposure, thus decreasing morbidity and allowing amore rapid recovery.
3. Preliminary data suggest that these therapies are effective but the length of follow-up in most studies is quite limited (on average 15–20months) and long-term efficacy is not established.
4. Acceptable candidates for thermal ablations are patients with advanced age, significant comorbidities and recurrence after prior NSS.
5. Experience with cryosurgery is more extensive than with RFA in the urologic literature.
6. Both ablative techniques cause tumor death by immediate cellular damage and delayed microcirculatory failure.
7. The ideal treatment parameters are yet to be fully determined; although most will double ablate (2 cycles) for a margin of safety.
8. Imaging concerns remain one of the greatest obstacles to ablative technologies. Real-time imaging is best achieved with intraoperative ultrasound;
9. Most ablations will error on overtreatment of the tumor to attain an adequate margin. For this reason, more nephrons may be lost during ablation than excision.

Front 130

What tumors are amenable to ablation?

Back 130

1. <3.5cm, peripheral, solid, exophytic, remote from major vascular and collecting system structures
2. These are the same characteristics
of the ideal tumor for NSS.

Front 131

What does heat sinking refer to?

Back 131

1. The dissipation of thermal energy by nearby vascular structures (more of a problem with RFA than cryo)
2. Animal data also suggest there is a greater risk of urinary collecting system injury and fistula formation with RFA than with cryosurgery.
3. The type of energy ablation used should be carefully considered for lesions close to the collecting system and larger intrarenal vessels.

Front 132

Are recurrence rates and re-treatment rates lower with cyro or RFA? What are reported recurrence/persistence rates following ablative techniques?

Back 132

- Cryo
- Reported recurrence and/or persistence rates following ablative techniques are between 5% and 12% per the AUA guidelines

Front 133

What is the problem with imaging and RFA?

Back 133

After RFA, lack of enhancement of an ablated mass does not always correspond with histologic absence of tumor on biopsy

Front 134

What is the definition of cytoreductive nephrectomy?

Back 134

1. Removal of the kidney in patients with metastatic RCC is termed cytoreductive.
2. In the immunotherapy era, some patients were unable to proceed to systemic therapy, calling into question the benefit of cytoreduction.
3. In a randomized prospective trial sponsored by SWOG, the role of cytoreductive nephrectomy was shown to be associated with a statistically significant improved overall survival.
4. Selection is key in identifying thosemost likely to benefit fromcytoreductive nephrectomy.
5. Patients should have a good performance status, lesser metastatic disease, and no/minimal
hepatic or osseous metastases. CNS metastases are considered a contraindication with rare exception.
6. Cytoreduction has been successfully performed laparoscopically; however, a laparoscopic
approach should not compromise the primary goal, which remains excision of all localized disease including involved regional lymph nodes.
7. For locally advanced RCC involving adjacent organs, such as colon or spleen, cytoreduction is often necessary to control local symptoms. En bloc resection is the primary aim. In selective patients, such as those with solitary regional metastases, long-term survival is possible with wide excision.
8. The role of cytoreductive nephrectomy in the setting of TKIs is unclear but under study.

Front 135

When should adjuvant tx be given after nephrectomy?

Back 135

- Adjuvant tx is not recommended when RCC is completely resected

Front 136

What is the long term survival in pts with a solitary met from RCC?

Back 136

-Long term survival is achieved with excision of the primary tumor and the met.
- Preferred tx is radical nx and met resection if it is known at the same time as primary RCC

Front 137

What is the preferred tx of a solitary recurrence after radical nx?

Back 137

Met resection

Front 138

In pts with RCC and mult mets, what is the preferred tx?

Back 138

- For pts with resectable primary tumor and are medically fit, standard tx is cytoreductive nx followed by systemic tx. This is based on 2 randomized trials that show RN follwed by interferon improves time to progression and overall survival compared to interferon alone

Front 139

If a pt is dx with RCC and mult mets but is not a candidate for radical nx, what are tx options?

Back 139

- Surveillance
- Systemic tx
- Palliative embolization
- Debulking by partial resection is usually not indicated

Front 140

What are systemic tx options for RCC mets?

Back 140

- IL-2 (interleukin-2)
- Tyrosine kinase inhibitor
- mTOR inhibitor
- Bevacizumab and interferon
- Chemotx

Front 141

How do you treat RCC mets to brain?

Back 141

- Brain mets are tx with radiation or surgical resection bc systemic tx are generally ineffective against brain mets due to blood-brain barrier

Front 142

When can you use radiation for RCC mets?

Back 142

Palliation of bone and brain mets. It is not effective against the primary tumor

Front 143

What are systemic therapies for mRCC?

Back 143

1. Multiple adjuvant therapies have been assessed to reduce the risk of recurrence following resection of high-risk disease. Of these, only 1 positive trial has been published using autologous tumor vaccine (Jachamet al). Unfortunately, there were several design and enrollment concerns that limit this study’s clinical relevance. Therefore, at the current time, the only role
for adjuvant treatment of high-risk RCC is in the context of a clinical trial.
2. There is no convincing role for hormonal or radiation therapies in mRCC other than for palliation.
3. RCC is a chemoresistant tumor. Multiple studies have demonstrated a low (2%–6%) response rate to multimodal chemotherapeutic approaches.
4. Immunologic therapies have been the preferred treatment for mRCC for the last 2–3 decades. These strategies include cytokines, adoptive immunotherapies and vaccines.

Front 144

What are cytokine tx options?

Back 144

1. Interferon (IFN) alpha – a member of a group of pleiotropic proteins with antiviral, immunomodulatory and antiproliferative activities related to modulation of gene expression in selected cell populations. Overall response rates in mRCC to single agent IFN alpha are approximately 12%, with only 1.8% complete responses and a median overall survival of 5–15months.
2. Interleukin-2 (IL-2) – a T-cell growth factor. In the US, IL-2 was approved on the basis of data from a high-dose infusion protocol.
3. Cytokine combination therapy with IL-2 and IFN alpha suggest response rates of approximately 19%, but with no improvement in overall survival.

Front 145

What type of therapy is IL-2? What is it?

Back 145

- Immunotherapy/cytokine
- It is a cytokine, T-cell growth factor produced by activated T cells that binds to the IL-2 receptor whcih causes expansion of cytotoxic T cells

Front 146

What is IL-2 used to treat? What are its response rates? What is median overal survival? What are its side effects?
Who studied this drug?

Back 146

- It is used to treat clear cell RCC (other types of RCC usually do not respond)
- It is the only drug that has achieved durable remission in pts with metastatic clear cell RCC
- The overall response rate to IL-2 is approximately 15% with durable complete responses in 6%–8%.
- Median overall survival is 12-18mos. Patients with Clear Cell RCC responded best
- Side effects: hypotension, oliguria, multiorgan failure fever, chills, weight gain, fluid retention, reversible renal and hepatic insufficiency,

Front 147

What is the most effective regimen for IL-2? What other comorbidities must you take into consideration?

Back 147

- High-dose bolus IL-2
- IV IL-2(600,000-720,000IU/kg) q8hrs x 14 doses.
- 2 cycles are given with 5-9 days of rest between cycles
- No brain mets, adequate cardiac, renal, and pulmonary function
- In responding pts, this 2 cycle course is repeated every 6-12 weeks

Front 148

What are targeted therapies?

Back 148

1. With the identification of the VHL gene and subsequent delineation of portions of its pathways,
various agents have been investigated which seek to perturb the VEGF pathway for therapeutic benefit.
2. Bevacizumab – an IgG1monoclonal antibody that binds all isoforms of VEGF, thereby inhibiting its signaling by sequestering the circulating ligand. High-dose bevacizumab has been shown to increase time to progression compared to placebo, although it did not improve overall survival. This was among the first proof of principles that demonstrated that therapies targeting the VEGF pathway could be used for therapeutic benefit. It is currently not being used as a single agent inmRCC.
3. Sunitinib – an oral tyrosine kinase receptor inhibitor approved formRCC that blocks multiple kinases, including VEGFR-2, PDGF, cKit and Flt-3. In phase III trials, sunitinib has been shown to have a higher response rate asmeasured by tumor regression
(30%–40%) when compared directly to IFN, with a statistically significant improvement in progression-free survival. Side effects include fatigue, hypertension, rash,
diarrhea and, potentially, thyroid and left ventricular dysfunction.
4. Sorafenib – an oral tyrosine and Raf kinase receptor inhibitor approved formRCC. Has demonstrated improvements in progression-free survival, tumor regression and stabilization of disease in phase II/III trials. Side effects include nausea, vomiting, diarrhea, fatigue, hypertension, and hand and foot syndrome.
5. Temsirolimus – an intravenous inhibitor ofmTOR (mammalian target of rapamycin). This agent blocks translation of HIF1. It has been shown in a phase III study of poor risk patients with mRCC to improve overall survival vs IFN. It is not yet approved for use in RCC.
6. Other recently approvedmedications for mRCC include pazopanib (TKI) and everolimus (oral mTOR inhibitor).

Front 149

What type of therapy is mTOR inhibitor? What is it? What are names of mTORs?

Back 149

- mTOR is a protein that regulates HIF and VEGF. So mTOR inhibitors reduce angiogenesis and cell proliferation
- Temsirolimus and everolimus

Front 150

What are mTOR inhibitors used to treat? What are its response rates?

Back 150

- Temsirolimus is approved for tx of advanced RCC in pts with predictors of short survival. It improved median survival and progression free survival by 3 mos
- Temsirolimus is the only agent that has shown activity against non-celar cell RCC. It has achieved benefit in both clear cell and non-clear cell RCC
- Everolimus is approved to tx advanced RCC after failure of sorafenib or sunitinib. It was shown to improve progression free suvival by 2 mos

Front 151

What is the most effective regimen for mTORs?

Back 151

- Temsirolimus: 25mg IV qweek over 30-60 min. Give antihistamine before infusion
- Everolimus 10mg po qday

Front 152

What are its side effects of mTORs? What labs should you order during tx?

Back 152

- Side effects include rash, stomatitis (mouth ulcers), infections, asthenia, nausea, diarrhea, thrombocytopenia, neutropenia, hyperglycemia, elev creatinine, elev LFTs, hypophosphatemia
- CBC, BUN, creatinine, fasting serum glucose, lipid profile, LFTs, and serum phosphate

Front 153

What type of therapy is a Tyrosine Kinase inhibitor? What are names of these?

Back 153

- Tyrosine kinase inhibitors reduce angiogenesis and cell proliferation by inhibiting VEGFR, platelet derived growth factor receptor (PDGFR), and stem cell factor receptor (c-KIT)
- Sunitinib, sorafenib, and pazopanib are names of tyrosine kinase inhibitors

Front 154

What are tyrosine kinase inhibitors used to treat? What are its response rates?

Back 154

- These are used to treat metastatic RCC
- Appear to improve median progression free survival by 2-6 mos and median overall survival by 3-4 mos
- Sunitinib has been shown to have a higher tumor regression rate (30-40%) compared to IFN

Front 155

What is the most effective regimen for tyrosine kinase inhibitors? What are its side effects of tyrosine kinase inhibitors? What labs should you order during tx?

Back 155

- Sunitinib 50mg po qday. It is administered in cycles with each cycle consisting of 4 weeks on and 2 weeks off
- Sorafenib 400mg po BID
- Pazopanib 800mg po qday
- Side effects: hand and foot syndrome, GI, hypophosphatemia, hypothyroidism, HTN, proteinuria, bleeding, thrombocytopenia, alopecia, headache, fatigue, arterial embolic event (stroke, MI)
- During tx, check CBC, urinalysis for proteinuria, thyroid function tests, BMP, LFTs, consider ejection fraction

Front 156

What is bevacizumab? What does it do?

Back 156

- Recombinant monoclonal antibody
- It inhibits angiogenesis and tumor growth by binding to and neutralizing VEGF-A

Front 157

What is bevacizumab used to treat? What are its response rates?

Back 157

- Bevacizumab is used with interferon
- Used to tx metastatic RCC
- Has been shown to increase time to progression
- In pts with clear cell RCC, bevacizumab with interferon improved progression free survival by 3-5 mos compared to interferon alone

Front 158

What are its side effects of bevacizumab?

Back 158

- dry mouth, headache, HTN, stomatitis, GI, minor bleeding, poor wound healing.
- To avoid poor wound healing, stop at least 28days before elective surgery and resume 28 days after surgery

Front 159

What is adoptive immunotherapy?

Back 159

1. This strategy involves the transfer of autologous lymphocytes for the treatment of mRCC, including lymphokine activated killer (LAK) cells, T cells and tumor-infiltrating lymphocytes (TIL).
2. Randomized trials combining cytokines with adoptive immunotherapy have not shown any improvement in survival. Adoptive immunotherapy remains experimental.

Front 160

What are vaccine tx?

Back 160

1. The use of active specific immunotherapy to indirectly enhance the immune response.
2. Vaccines used in RCC include autologous tumor lysate combinations, tumor fused with dendritic cells (an antigen-presenting cell), dendritic cell vaccines and heat shock proteins.
3. No vaccine trial has demonstrated improvement in survival and therefore these remain investigational.

Front 161

When comparing systemic agents, what are the preferred tx?

Back 161

- IL-2 is the only drug that has achieved durable remission in pts iwth metastatic clear cell RCC
- Temsirolimus is the only agent that has shown activity against non-clear cell RCC
- If the initial agent fails, try a different agent or clinical trial. If the pts has specifically failed sorafenib or sunitinib, everolimus may be tried

Front 162

What are multimodal therapy?

Back 162

1. Most cases of advanced RCC are not treated by any one modality alone. The combination of integrated surgery of the primary tumor with selective surgery on metastases and combination or sequential targeted systemic therapies is aimed at prolonging survival in patients with mRCC. Randomized trials are continuing to validate and refine these strategies.

Front 163

What can happen when functional renal tissue is removed? How long does it take to develop?

Back 163

- A glomerular hyperfiltration occurs in the remaining tissue to restore filtration capacity
- Prolonged glomerular hyperfiltration may cuase renal injury that leads to focal segmental glomerulosclerosis and progressive renal failure
- Hyperfiltration injury may take more than 10 years to develop

Front 164

What is a sign of hyperfiltration injury?

Back 164

- Proteinuria. It precedes pathologic and clinical evidence of renal damange

Front 165

When is hyperfiltration injury more likely to occur?

Back 165

- If more than 75% of the functional renal tissue is removed.
- When </= 50% of the renal tissue is removed, hyperfiltration is uncommon. So in kidney donors, GFR should not significantly decline in 20 years

Front 166

What characteristics increase the risk of hyperfiltration injury?

Back 166

- Removal of 75% of functional kidney
- High protein diet
- Obesity
- Steroid use
- HTN
- Hyperlipidemia
- Poorly controlled DM

Front 167

What are ways to decrease the risk of hyperfiltration injury?

Back 167

- ACE-Inhibitors may help prevent hyperfiltration injury by lowering intraglomerular pressure. Some suggest beginning ACEI if 24hr urine protein is >150mg
- Weight loss in obese pt
- Low protein, low sodium diet
- Strict control of DM, HTN, HL
- Avoid steroid use
- Avoid nephrotoxins (NSAIDs)

Front 168

How should you follow up after radical/partial nx?

Back 168

- H&P, blood pressure, LFTs, alk phos, serum calcium, BUN, and creatinine every 6 mos for 2 eyars then every year
- Abd CT/MRI and chest imaging at 6 mos post-op then every 1-2 yrs
- Bone scans and brain MRI when clinically indicated
- In pts with solitary kidney, 24hr urine for creatinine, protein, ad volume to assess for hyperfiltration
- Pts with solitary kidney should be advised that participation in contact/collision sports places the kidney at risk for traumatic injury.

Front 169

What is the rate of local recurrence in renal fossa after radical or partial nx?

Back 169

<2%. Resection of a local recurrence in absence of metastatic disease can achieve long term survival

Front 170

What is the recurrence rate in the contralateral kidney?

Back 170

1.2%

Front 171

What are the definitions of ECOG performance status 0-4?

Back 171

0=Normal activity
1=Symptomatic but ambulatory
2=Bedridden <50% of the time
3=Bedridden >50% of the time
4=Completely bedridden

Front 172

What are poor prognostic factors for RCC?

Back 172

1. Higher ECOG PS
2. Symptomatic tumor
3. High tumor stage
4. Large tumor size
5. Collecting system invasion
6. High grade tumor
7. Sarcomatoid features
8. Tumor necrosis
9. Microvascular invasion
10. Histology - prognosis is worse for collecting duct, medullary, Type 2 papillary, and unclassified RCC
11. Tumor thrombus envading the vena cava wall
12. Residual tumor (positive margin or incomplete resection)
13. Presence of mets - adrenal, lymph nodes, or distant mets

Front 173

What is survival based on TNM stage T1aN0M0 after RN or PN?

Back 173

5 yr disease specific survival is 95-100%

Front 174

What is survival based on TNM stage T1bN0M0 after RN or PN?

Back 174

5 yr disease specific survival is 88-92%

Front 175

What is survival based on TNM stage T2N0M0 after RN or PN?

Back 175

5 yr disease specific survival is 88

Front 176

What is survival based on TNM stage T3aN0M0 in perirenal or sinus fat but no venous tumor thrombus after RN?

Back 176

5 yr overall survival is 47-68%

Front 177

What is survival based on TNM stage T3N0M0 in with venous tumor thrombus after RN and thrombectomy?

Back 177

5 yr overall survival is 43-72%

Front 178

What is survival based on TNM stage T4 not into contiguous organs after RN?

Back 178

5 yr overall survival is 28%

Front 179

What is survival based on TNM stage T4 into contiguous organs after RN?

Back 179

5 yr overall survival is <5%

Front 180

What is survival based on TNM stage N+M0 after RN?

Back 180

5 yr overall survival is 0-33%

Front 181

What is survival of pt with solitary recurrence develops after nephrectomy for M0 tumor after treatment of recurrence?

Back 181

5 yr overall survival is 13-54%

Front 182

What is survival of pt with solitary met present at initial diagnosis after radical nx and treatmetn of met?

Back 182

5 yr overall survival is 0-20%

Front 183

What is survival of pt with multiple unresectable mets?

Back 183

5 yr overall survival is 0%

Front 184

What is survival based on UCLA system in T1N0M0, ECOG 0, Fuhrman grade 1-2 tx with radical nx?

Back 184

5 year disease specific survival is 91%

Front 185

What is survival based on UCLA system in T1N0M0, ECOG 0, Fuhrman grade 3-4 tx with radical nx?

Back 185

5 year disease specific survival is 80%

Front 186

What is survival based on UCLA system in T1N0M0, ECOG >/=1, Fuhrman grade any, tx with radical nx?

Back 186

5 year disease specific survival is 80%

Front 187

What is survival based on UCLA system in T2N0M0, ECOG any, Fuhrman grade any, tx with radical nx?

Back 187

5 year disease specific survival is 80%

Front 188

What is survival based on UCLA system in T3N0M0, ECOG 0, Fuhrman grade any, tx with radical nx?

Back 188

5 year disease specific survival is 80%

Front 189

What is survival based on UCLA system in T3N0M0, ECOG >/=1, Fuhrman grade 1, tx with radical nx?

Back 189

5 year disease specific survival is 80

Front 190

What is survival based on UCLA system in T3N0M0, ECOG >/=1, Fuhrman grade >/=2, tx with radical nx?

Back 190

5 year disease specific survival is 55%

Front 191

What is survival based on UCLA system in T4N0M0, ECOG any, Fuhrman grade any, tx with radical nx?

Back 191

5 year disease specific survival is 55%

Front 192

What is survival based on UCLA system in N1M0 (only 1 node met), ECOG any, Fuhrman grade any, tx with radical nx and immunotx?

Back 192

5 year disease specific survival is 32%

Front 193

What is survival based on UCLA system in N1M0 (>1 node met or M1), ECOG 0, Fuhrman grade 1-2, tx with radical nx and immunotx?

Back 193

5 year disease specific survival is 32%

Front 194

What is survival based on UCLA system in N1M0 (>1 node met or M1), ECOG 0, Fuhrman grade 3-4, tx with radical nx and immunotx?

Back 194

5 year disease specific survival is 20%

Front 195

What is survival based on UCLA system in N1M0 (>1 node met or M1), ECOG >/=1, Fuhrman grade 1-3, tx with radical nx and immunotx?

Back 195

5 year disease specific survival is 20%

Front 196

What is survival based on UCLA system in N1M0 (>1 node met or M1), ECOG >/=1, Fuhrman grade 4, tx with radical nx and immunotx?

Back 196

5 year disease specific survival is 0%

Front 197

What is a Bosniak I cyst? What is its cancer risk? How is it treated?

Back 197

- Simple cyst with no enhancement, smooth, empty
- 0% cancer risk
- No tx unless symptomatic, no follow-up needed

Front 198

What is a Bosniak IIF cyst? What is its cancer risk? How is it treated?

Back 198

- No enhancement, may be hyperdense (protein/blood), few septa, thin linear calcification
- <10% cancer risk
- No tx, but follow

Front 199

What is a Bosniak III cyst? What is its cancer risk? How is it treated?

Back 199

- Thick irregular wall or septa, thick calcifications, moderate septa, may enhance, mild to moderate heterogeneity
- 50% cancer risk
- Resect

Front 200

What is a Bosniak IV cyst? What is its cancer risk? How is it treated?

Back 200

- Enhancing nodule
- 80-90% cancer risk
- Resect

Front 201

Clues for the DDx of radiographic renal masses:
1. Fever, flank pain, pyuria
2. "Problematic stones"
3. Spontaneous RP bleed
4. Speckeld Ca++
5. Fat by MRI, CT or US
6. Calcified rounded hilar lesion
7. Cystic lesions in middle-aged female

Back 201

1. Think inflammatory (abscess or pyelonephritis)
2. Think XGP
3. Think underlying RCC
4. Think of possible RCC
5. AML or liposarcoma
6. Renal arter aneurysm
7. Think of cystic nephromas

Front 202

What imaging should be routine in RCC metastatic work-up?

Back 202

CXR, 3 phase CT or MRI with gadolinium. Bone scans, CNS imaging and chest CT should be based on symptoms and labs.

Front 203

Is PET useful for evaluating RCC?

Back 203

PET has poor sensitivity for routine use in RCC

Front 204

Principles of surgery for locally advanced RCC?

Back 204

1. The principles of surgery for locally advanced RCC remain the same, excision of all localized disease.
2. In selective cases, NSS may be appropriate and feasible in the setting of node-positive disease
and/or venous involvement.
3. Principles of surgery for venous involvement include complete excision with full vascular control.
4. Involvement of the IVC with RCC occurs in 4%–10% of patients.
5. In cases of suspected venous involvement, it is imperative to determine the highest level of
involvement preoperatively. This is often best staged with an MRV.
6. The prognostic significance of the level of involvement has been controversial.
7. 5-year survival for fully resected Mo RCC with IVC involvement is reported to be 50%–70%.
8. Preoperative angioinfarction may be useful in cases of arterialization of the thrombus or in patients with excessive hilar adenopathy, in whom ligating the artery firstmay be problematic.
9. For cases of level 1 thrombus, simple milking back of the clot into the renal vein with open or laparoscopic ligation proximally is often sufficient.
10. For cases of level 2 thrombus, control and sequential clamping of the IVC above and below the clot and the contralateral renal vein, after full exposure and ligation of lumbar veins, provides a bloodless field.

Front 205

What is the definition of metastasectomy

Back 205

1. Resection of synchronous or metachronous metastatic RCC (mRCC) is termed metastasectomy.
2. Aggressive surgical resection may be associated with favorable long-term survival.
3. Patients in whom metastasectomy is most often beneficial are those that have “favorable”
metastatic biology, including solitary lesions, pulmonary lesions and long disease-free intervals in the case of metachronous disease.
4. Those with multiple, hepatic and/or osseous metastases presenting with synchronous metastatic disease and/or a short disease-free interval are poorer candidates for metastasectomy.
5. The MSKCC criteria may be used to stratify the risk of metastasectomy or systemic therapy in patients with mRCC and include performance status, weight loss, serumcalcium, LDH, alkaline phosphatase, hemoglobin, platelets and sedimentation rates.
6. Local recurrence following radical nephrectomy is uncommon and occurs in about 2%. Only about 40% of local recurrences are isolated and the majority also has systemic disease, such that an extensive disease evaluation should be pursued.
7. Many local recurrences are in adjacent nodes which were not removed at the time of surgery. This emphasizes the importance of adequate preoperative evaluation and surgical resection.

Front 206

Who are good candidates for active surveillance?

Back 206

1. pts with small enhancing lesions who are elderly, have significant medical risks, or do not wish to have intervention
2. Offered the opportunity for serial radiographic surveillance to define the growth kinetics of untreated RCC
3. Collectively, there are approximately 900 small renal masses reported in the literature which have undergone a period of active surveillance for an average of nearly 3 years. In over half of these, pathology is available and in over 80%–90% RCC was present.

Front 207

How frequently should you image pts on active surveillance?

Back 207

Every 3-6 mos in the first 12 years and less frequently once stability or slow growth kinetics are established

Front 208

What are the growth kinetics and progression of RCC under active surveillance?

Back 208

1. The median rate of radiographic growth in most series is between 0.08 and 0.58 cm/year.
2. As many as 30% of small renal masses show no radiographic growth when followed over a median of 3 years.
3. The risk of metastatic progression in active surveillance series appears to be quite low at about 1%–2% at amedian follow-up of 3 years.
4. Most series are limited by their retrospective nature and selection biases.
5. Active surveillance of a small enhancing renal mass requires periodic contrast-based imaging, which is often more frequent initially (every 3–6months in the first 12 years) and less frequently once stability or slow growth kinetics are established.
6. Active surveillance, like any intervention, is a calculated risk.

Front 209

How does active surveillance effect survival?

Back 209

- Active surveillance followed by delayed intervention as necessary does not place pts at excessive risk for stage or grade progression

Front 210

What is the post-op surveillance in a pt with T1aN0M0 after radical/partial nx?

Back 210

- H&P, labs yearly
- CT undefined (may not need it)
- No CXR

Front 211

What is the post-op surveillance in a pt with T1bN0M0 after radical/partial nx?

Back 211

- H&P, labs yearly
- CT undefined (may not need it)
- CXR yearly

Front 212

What is the post-op surveillance in a pt with T2N0M0 after radical/partial nx?

Back 212

- H&P, labs yearly
- CT every 2 yrs
- CXR yearly

Front 213

What is the post-op surveillance in a pt with T3N0M0 after radical/partial nx?

Back 213

- H&P, labs every 6 mos for 3 years then yearly
- CT every 6 mos for 3 years then yearly
- CXR every 6 mos for 3 years then yearly

Front 214

What are other malignant neoplasms of the kidney

Back 214

1. Sarcomas
2. Renal lymphoma and leukemia
3. Metastatic tumors to the kidney
4. Carcinoids of the kidney
5. Wilms' tumor
6. PNET tumors

Front 215

How common are sarcomas of the kidney? When is the peak incidence?

Back 215

- Represent 1-2% of all malignant renal tumors
- Peak incidence in 5th decade

Front 216

Where are true renal sarcomas derived from?

Back 216

- Mesenchymal elements of the kidney and are typically surrounded by a pseudocapsule

Front 217

Where are mets from renal sarcomas most commonly found?

Back 217

- Lung
- Renal sarcomas often present with metastatic disease

Front 218

What is the median survival for high grade renal sarcoma? What are most important prognostic variables?

Back 218

- Median survival is months
- histology, grade, and margin status

Front 219

What is the most common type of renal sarcoma? What is 2nd most common type? How are they treated?

Back 219

- Leoimyosarcoma (50-60%) is the most common type and may have a female preponderance
- Liposarcomas are the 2nd most common type and must be distinguised from AML
- Wide and complete excision are mandatory

Front 220

Is renal involvement more common in Hodgkin's or non-Hodgkin's variant of lymphoma?

Back 220

1. More common with non-Hodgkin's lymphoma
2. Renal involvement in patients with hematologic malignancies is commonly found in 34% of patients dying of progressive lymphoma or leukemia at autopsy.
3. Usually a late manifestation of disease and represents hematogenous spread.
4. Often asymptomatic.

Front 221

What are CT characteristics of renal lymphoma?

Back 221

- Adjacent adenopathy particularly in uncommon locations for advanced kidny cancer such as in the mesentery
- Splenomegaly
- Diffuse enlargement of the kidney which maintains its renoform appearance

Front 222

How should you work-up a renal mass if lymphoma is suspected?

Back 222

1. Biopsy with flow cytometry
2. Tx is systemic and the kidney should not be removed
3. Histologically diffuse forms predominate over nodular forms.
4. Primary renal lymphoma is very rare, given the paucity of lymphoid tissue in the normal kidney

Front 223

What are clinical clues for renal lymphoma?

Back 223

- Fever
- Weight loss
- Fatigue
- "B" symptoms of lymphoma

Front 224

What is the most common abdominal malignancy in children?

Back 224

Wilm's tumor

Front 225

How frequent do you see Wilm's tumor in adults? At what age? How do you treat it?

Back 225

- 3%
- 15-20 years of age
- Treatment of adult Wilms’tumor is similar to that in a pediatric population and is multimodal

Front 226

Where are reninomas derived from?

Back 226

- These are benign tumors that arise from the specialized juxtaglomerular cells
- Juxtaglomerular tumors

Front 227

How do reninomas clinically present? When do the present and in whom?

Back 227

- Hypersecretion of renin leading to HTN, hypokalemia, polydipsia, polyuria, myalgias, and headaches
- Present in 3rd or 4th decade, female predominance
- Should exclude renal artery stenosis as cause of hyperreninemia

Front 228

What should you exclude as the diagnosis for reninomas? How are reninomas treated?

Back 228

- Exclude renal artery stenosis as cause of hyperreninemia
- Often at or near the corticomedullary junction
- Tx by excision. Mets are very rare

Front 229

Where do carcinoids of the kidney arise? What are they correlated to? How should you work these up?

Back 229

1. Arise from neuroendocrine cells, which are not normally present in the kidney.
2. This is therefore an exceptionally rare renal tumor.
3. Correlations have been made to horseshoe kidneys (increased relative risk 82-fold over normal kidneys).
4. Most patients are asymptomatic, a minority will present with carcinoid syndrome (flushing, wheezing, diarrhea).
5. Should consider evaluation for carcinoid elsewhere, such as with colonoscopy or upper GI endoscopy.

Front 230

What is a cystic nephroma (Multiloculated cystic nephroma -MLCN)?

Back 230

1. A benign lesion with a bimodal age distribution. Occurs in young (2–3 year old) boys and middle-aged (40–50) women.
2. More often symptomatic in adults.
3. By definition, all are multilocular and therefore appear as Bosniak III or IV cysts.
4. No reliable clinical or radiographic means of distinguishing MLCN from cystic RCC.
5. Managed surgically with NSS whenever clinically feasible.

Front 231

What is a leiomyoma?

Back 231

1. Slow-growing benign renal tumor arising from the capsule or peripelvic tissues. Rarely arises fromthe renal vein.
2. No reliable clinical or radiographic means of distinguishing from incidental RCC, although clearly capsular location should raise suspicion.

Front 232

What is a Metanephric Adenoma?

Back 232

1. Benign, occasionally symptomatic, with peak incidence in the 5th decade.
2. Small basophilic cells.
3. A few reported cases of associated malignant stromal elements.
4. No reliable clinical or radiographic means of distinguishing from incidental RCC. Therefore, excision, preferably by NSS, is indicated.

Front 233

What is a paraneoplastic syndrome?

Back 233

1. Renal tumors are capable of overproducing 1,25-dihydroxycholecalciferol, renin, erythropoietin
and/or various prostaglandins, whichmay case amyriad of constitutional symptoms.
2. Hypercalcemiamay occur in up to 13%of patients with RCC and can be due to either bony
involvement or the production of parathyroid hormone-like peptides. Signs of hypercalcemia
include nausea, anorexia, fatigue and decreased deep tendon reflexes.Management includes
hydration, diuretics, and selective use of bisphosphonates and steroids.
3. Hypertension can be due to local compression of the renal artery, arteriovenous fistula or
overproduction of renin.
4. Polycythemia can be due to overproduction of erythropoietin.
5. Nonmetastatic hepatic dysfunction (Stauffer’s syndrome) has been reported in 3%–20%of
RCC cases and is associated with an increase in serumalkaline phosphatase, prothrombin
time and/or elevated bilirubin. Itmay also be due to elevations in interleukin-6.
6. In general, paraneoplastic syndromes associated with RCC require nephrectomy.