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Kidney Renal Cell Cancer Cure - Kidney Renal Cell Cancer Medicine Drug
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Renal cell carcinoma (RCC) is the most common form of kidney cancer
arising from the renal tubule. It is the most common
type of kidney cancer in adults. Initial treatment is surgery.
It is notoriously resistant to radiation therapy and chemotherapy,
although some cases respond to immunotherapy. The advent of
targeted cancer therapies such as sunitinib has vastly
improved the outlook for treatment of RCC.
Contents [hide]
1 Signs and symptoms
2 Causes
3 Pathology
4 Radiology
5 Treatment
5.1 Watchful waiting
5.2 Surgery
5.3 Percutaneous therapies
5.4 Radiation therapy
5.5 Medications
5.6 Chemotherapy
5.7 Vaccine
5.8 Cryoablation
6 Prognosis
7 See also
8 External links
9 References
[edit] Signs and symptoms
The classic triad is hematuria (blood in the urine), flank pain and
an abdominal mass. This is now known as the 'too late triad' because
by the time patients present with symptoms, their disease is often
advanced beyond a curative stage. Today, the majority of renal tumors
are asymptomatic and are detected incidentally on imaging, usually
for an unrelated cause.
Other signs may include:
Abnormal urine color (dark, rusty, or brown) due to blood in the urine
Weight loss, malnourished appearance
The presenting symptom may be due to metastatic disease, such as a
pathologic fracture of the hip due to a metastasis to the bone
Enlargement of one testicle known as varicocele (usually the left,
due to blockage of the left gonadal vein by tumor invasion of the left
renal vein -- the right gonadal vein drains directly into the
inferior vena cava)
Vision abnormalities
Pallor or plethora
Hirsutism - Excessive hair growth (females)
Constipation
High blood pressure
Elevated calcium levels (Hypercalcemia)
[edit] Causes
Renal cell carcinoma affects about three in 10,000 people, resulting
in about 31,000 new cases in the US per year. Every year, about
12,000 people in the US die from renal cell carcinoma. It is more
common in men than women, usually affecting men older than 55.
Kidney cancer both RCC & TCC currently is diagnosed in some 6,600
people in Britain/UK per annum and some 3,600 people who die are
recorded as having died of kidney cancer in a given year. The
morbidity rate recorded is thought to underestimate the percentage
who die of kidney cancer. Often the cause of death recorded on the
death certificate may not mention kidney cancer but the subsequent
metastases. It is clear that well over 50% of those diagnosed with
kidney cancer in Britain will die of the disease or as a result of
the disease.
Why the cells become cancerous is not known. A history of smoking
greatly increases the risk for developing renal cell carcinoma. Some
people may also have inherited an increased risk to develop renal
cell carcinoma, and a family history of kidney cancer increases the risk.
Increasingly there is a belief that inhalation of a diversity of
chemicals may be causal and it is also noted that there is a steady
increase in diagnosis in women. That a disproportionate percentage of
those diagnosed with kidney cancer are obese is increasingly believed
to be a significant factor.
People with von Hippel-Lindau disease, a hereditary disease that also
affects the capillaries of the brain, commonly also develop renal
cell carcinoma. Kidney disorders that require dialysis for treatment
also increase the risk for developing renal cell carcinoma.
[edit] Pathology
Renal cell carcinoma
Renal cell carcinomaGross examination shows a yellowish,
multilobulated tumor in the renal cortex, which frequently contains
zones of necrosis, hemorrhage and scarring.
Light microscopy shows tumor cells forming cords, papillae, tubules
or nests, and are atypical, polygonal and large. Because these cells
accumulate glycogen and lipids, their cytoplasm appear
"clear", lipid-laden, the nuclei remain in the middle of
the cells, and the cellular membrane is evident. Some cells may be
smaller, with eosinophilic cytoplasm, resembling normal tubular
cells. The stroma is reduced, but well vascularized. The tumor
compresses the surrounding parenchyma, producing a pseudocapsule.[1]
Secretion of vasoactive substances (e.g. renin) may cause arterial
hypertension, and release of erythropoietin may cause erythrocytosis
(increased production of red blood cells).
[edit] Radiology
A CT scan showing bilateral renal cell carcinomasThe characteristic
appearance of renal cell carcinoma (RCC) is a solid renal lesion
which disturbs the renal contour. It will frequently have an
irregular or lobulated margin. 85% of solid renal masses will be RCC.
10% of RCC will contain calcifications, and some contain macroscopic
fat (likely due to invasion and encasement of the perirenal fat).
Following intravenous contrast administration (computed tomography or
magnetic resonance imaging), enhancement will be noted, and will
increase the conspicuity of the tumor relative to normal renal parenchyma.
A list of solid renal lesions includes:
renal cell carcinoma
metastasis from an extra-renal primary neoplasm
renal lymphoma
squamous cell carcinoma
juxtaglomerular tumor (reninoma)
transitional cell carcinoma
angiomyolipoma
oncocytoma
Wilm's tumor
In particular, reliably distinguishing renal cell carcinoma from an
oncocytoma (a benign lesion) is not possible using current medical
imaging or percutaneous biopsy.
Renal cell carcinoma may also be cystic. As there are several benign
cystic renal lesions (simple renal cyst, hemorrhagic renal cyst,
multilocular cystic nephroma, polycystic kidney disease), it may
occasionally be difficult for the radiologist to differentiate a
benign cystic lesion from a malignant one. A famous radiologist named
Dr. Morton Bosniak developed a classification system for cystic renal
lesions that classifies them based specific imaging features into
groups that are benign and those that need surgical resection[2]. At
diagnosis, 30% of renal cell carcinoma has spread to that kidney's
renal vein, and 5-10% has continued on into the inferior vena cava[3].
Percutaneous biopsy can be performed by a radiologist using
ultrasound or computed tomography to guide sampling of the tumor for
the purpose of diagnosis. However this is not routinely performed
because when the typical imaging features of renal cell carcinoma are
present, the possibility of an incorrectly negative result together
with the risk of a medical complication to the patient make it
unfavorable from a risk-benefit perspective.This is not completely
accurate, there are new experimental treatments.
[edit] Treatment
If it is only in the kidneys, which is about 40% of cases, it can be
cured roughly 90% of the time with surgery. If it has spread outside
of the kidneys, often into the lymph nodes or the main vein of the
kidney, then it must be treated with adjunctive therapy, including
cytoreductive surgery
[edit] Watchful waiting
Small renal tumors represent the majority of tumors that are treated
today by way of partial nephrectomy. The average growth of these
masses is about 4-5 mm per year, and a significant proportion (up to
40%) of tumors less than 4cm in diameter are benign. More centers of
excellence are incorporating needle biopsy to confirm the presence of
malignant histology prior to recommending definitive surgical
extirpation. In the elderly, patients with co-morbidities and in poor
surgical candidates, small renal tumors may be monitored carefully
with serial imaging. Most clinicians conservatively follow tumors up
to a size threshold between 3-5 cm, beyond which the risk of distant
spread (metastases) is about 5%.
[edit] Surgery
Surgical removal of all or part of the kidney (nephrectomy) is
recommended.[citation needed] This may include removal of the adrenal
gland, retroperitoneal lymph nodes, and possibly tissues involved by
direct extension (invasion) of the tumor into the surrounding
tissues. In cases where the tumor has spread into the renal vein,
inferior vena cava, and possibly the right atrium (angioinvasion),
this portion of the tumor can be surgically removed, as well. In case
of metastases surgical resection of the kidney ("cytoreductive
nephrectomy") may improve survival[4], as well as resection of a
solitary metastatic lesion.
[edit] Percutaneous therapies
Percutaneous, image-guided therapies, usually managed by
radiologists, are being offered to patients with localized tumor, but
who are not good candidates for a surgical procedure. This sort of
procedure involves placing a probe through the skin and into the
tumor using real-time imaging of both the probe tip and the tumor by
computed tomography, ultrasound, or even magnetic resonance imaging
guidance, and then destroying the tumor with heat (radiofrequency
ablation) or cold (cryotherapy). These modalities are at a
disadvantage compared to traditional surgery in that pathologic
confirmation of complete tumor destruction is not possible.
[edit] Radiation therapy
Radiation therapy is not commonly used for treatment of renal cell
carcinoma because it is usually not successful. Radiation therapy may
be used to palliate the symptoms of skeletal metastases.
[edit] Medications
Medications such as alpha-interferon and interleukin-2 (IL-2) have
been successful in reducing the growth of some renal cell carcinomas,
including some with metastasis. Studies have demonstrated that IL-2
offers the possibility of a complete and long-lasting remission in
these diseases. In addition, the anti-VEGF monoclonal antibody
bevacizumab has been shown to be promising in advanced disease.
Sorafenib (Nexavar) was FDA approved in December 2005 for treatment
of advanced renal cell cancer, the first receptor tyrosine kinase
(RTK) inhibitor indicated for this use.
A month later, Sunitinib (Sutent) was approved as well.
Sunitiniban oral, small-molecule, multi-targeted (RTK)
inhibitorand sorafenib both interfere with tumor growth by
inhibiting angiogenesis as well as tumor cell proliferation.
Sunitinib appears to offer greater potency against advanced RCC,
perhaps because it inhibits more receptors than sorafenib. However,
these agents have not been directly compared against one another in a
single trial. [1][2]
Recently the first Phase III study comparing an RTKI with cytokine
therapy was published in the New England Journal of Medicine. This
study proved that Sunitinib offers superior efficacy compared with
interferon-a. Progression-free survival (primary endpoint) was more
than doubled. The benefit for sunitinib was significant across all
major patient subgroups, including those with a poor prognosis at
baseline. 28% of sunitinib patients had significant tumor shrinkage
compared with only 5% of patients who received interferon-a. Although
overall survival data are not yet mature, there is a clear trend
toward improved survival with sunitinib. Patients receiving sunitinib
also reported a significantly better quality of life than those
treated with IFNa. [5] Based on these results, lead investigator Dr.
Robert Motzer announced at ASCO 2006 that Sunitinib is the new
reference standard for the first-line treatment of mRCC. [6]
Temsirolimus (CCI-779) is an inhibitor of mTOR kinase (mamallian
target of rapamycin) that was shown to prolong overall survival vs.
interferon-a in patients with previously untreated metastatic renal
cell carcinoma with three or more poor prognostic features. The
results of this Phase III randomized study were presented at the 2006
annual meeting of the American Society of Clinical Oncology (www.ASCO.org).
[edit] Chemotherapy
Chemotherapy may be used in some cases, but cure is unlikely unless
all the cancer can be removed with surgery. The use of Tyrosine
Kinase (TK) inhibitors, such as Sunitinib and Sorafenib, and
Temsirolimus are described in a different section.
[edit] Vaccine
In November 2006, it was announced that a vaccine had been developed
and tested with very promising results.(See [3]) The new vaccine,
called TroVax, works by harnessing the patient's own immune system to
fight the disease. Further vaccine trials are underway.
[edit] Cryoablation
This involves destroying the kidney tumor without surgery, by
freezing the tumor. The process can remove 95% of tumors in one
treatment and can be tolerated by patients who are not good
candidates for surgery (older or weak patients). [7].
[edit] Prognosis
The outcome varies depending on the size of the tumor, whether it is
confined to the kidney or not, and the presence or absence of
metastatic spread. The Fuhrman grading, which measures the
aggressiveness of the tumor, may also affect survival, though the
data is not as strong to support this.
The five year survival rate is around 90-95% for tumors less than 4
cm. For larger tumors confined to the kidney without venous invasion,
survival is still relatively good at 80-85%. For tumors that extend
through the renal capsule and out of the local fascial investments,
the survivability reduces to near 60%. If it has metastasized to the
lymph nodes, the 5-year survival is around 5 % to 15 %. If it has
spread metastatically to other organs, the 5-year survival rate is
less than 5 %.
For those that have tumor recurrence after surgery, the prognosis is
generally poor. Renal cell carcinoma does not generally respond to
chemotherapy or radiation. Immunotherapy, which attempts to induce
the body to attack the remaining cancer cells, has shown promise.
Recent trials are testing newer agents, though the current complete
remission rate with these approaches are still low, around 12-20% in
most series.
[edit] See also
Stauffer syndrome
[edit] External links
Photo at: Atlas of Pathology
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