Sunday, September 30, 2012

Abdominal Masses in Neonates and Children

Polycystic kidney
Distended bladder
Ovarian cyst
Wilms’ tumor
Mesoblastic nephroma
Adrenal hemorrhage
Renal vessel thrombosis
Pyloric stenosis
Germ cell tumors
Hepatic lesions
Sacrococcygeal teratoma

Pediatric “Urgencies”

Prune-belly syndrome
Imperforate anus
Urethral prolapse
Urinary tract infections

Pediatric Emergencies

Acute scrotum
Ambiguous genitalia
Renal vein thrombosis
Renal artery thrombosis
Adrenal hemorrhage
Posterior urethral valves
Child abuse
Abdominal mass

Testicular torsion

Testicular torsion occurs when a testicle rotates, twisting the spermatic cord that brings blood to the scrotum. The reduced blood flow causes sudden and often severe pain and swelling. Testicular torsion is most common between ages 12 and 16, but it can occur at any age, even before birth.
Testicular torsion usually requires emergency surgery. If treated within a few hours, the testicle can usually be saved. But waiting longer can cause permanent damage and may affect the ability to father children. When blood flow has been cut off for too long, a testicle may become so badly damaged it has to be removed.

With testicular torsion, the testicle twists on the spermatic cord. This cuts off blood flow to the testicle and causes sudden, severe pain.
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Instant Anatomy

The Rational Clinical Examination 2009

Saturday, September 29, 2012

AUA recommendations: Urologic Surgery Antimicrobial Prophylaxis

The recommendations provided in this document, including specific indications and agents enumerated in the Tables, can assist urologists in the appropriate use of periprocedural antimicrobial prophylaxis.

Perforation of the Bladder

Perforation of the bladder may occur during TURP. The incidence of perforation is estimated at 1.1%. Perforations are most often made by the cutting loop or the knife electrode, although the tip of the resectoscope is sometimes responsible. Overdistension of the bladder with irrigating fluid can also result in a perforation. Most perforations are extraperitoneal. In the awake patient, pain may occur in the periumbilical, inguinal, or suprapubic region. If the
irrigation fluid fails to return as it normally does, perforation of the prostatic capsule is suspected. Occasionally, damage to the wall of the bladder may cause an intraperitoneal perforation, or a large extraperitoneal perforation may extend into the peritoneum. In such cases, pain might be referred from the diaphragm to the precordial region or the shoulder, or may be more generalized to the upper abdomen. Additional warning signs or symptoms may include pallor, diaphoresis دوخة, abdominal rigidity, nausea, vomiting, hypotension, or hypertension. Hiccups and shortness of breath may result from subdiaphragmatic irritation. Intraperitoneal
fluid will usually be extruded by the kidney although catheter drainage may be necessary. Significant extravasation may need to be drained suprapubically.

Hypothermia During Transurethral Resection of the Prostate

Geriatric patients tolerate hypothermia poorly. There is an age-related decline in the function of the autonomic nervous system and in the ability to increase heat production, which results in thermoregulatory impairment. The constant irrigation of cold fluid through the bladder, in addition to its intravascular absorption, can rapidly lower core body temperature. Furthermore, these patients are in cold operating rooms, and receive intravenous fluids at ambient temperature. The anesthetic technique used, general or regional, does not appear to influence intraoperative hypothermia. However, the use of warm intravenous and irrigating fluids, warming mattresses, and even warmed anesthetic gases, will help minimize the problem of excessive heat loss. Shivering, a direct consequence of hypothermia, causes increased oxygen consumption. Therefore, supplemental oxygen should be used in every patient. Shivering also increases venous pressure and promotes hemorrhage. Maintaining body temperature is an important consideration in providing for optimal care of TURP patients.


A number of irrigants are used in the genitourinary system during urologic procedures. These include irrigants used to dissolve stones, that is, renacidin, Suby’s Solution G, and irrigants used for endoscopic procedures, which include water, glycine, sodium chloride, sorbatol, and urea. Each one of these irrigants may have significant untoward effects particularly if excessive absorption occurs.

With the use of renacidin or Suby’s Solution G, magnesium intoxication may occur with increased salivation followed by hypotension, seizures, and coma. It is particularly dangerous to utilize these solutions in the presence of infection as sepsis may be a sequelae.

The use of water, glycine, sorbatol, and urea as irrigants may result in volume overload and severe hyponetremia—termed the transurethral resection syndrome. Significant volume overload
results in an increased pulse pressure, bradycardia and in the case of severe hyponetremia, visual disturbances followed by seizures, coma, and death. The correction of these abnormalities, if hyponetremia is a major component, includes diuresis with restoration of systemic sodium. In severe cases of hyponatremia in patients who are symptomatic, half of the sodium deficit is replaced with hypertonic saline. It should be noted that diuretics do not work in patients with severe hyponetremia. Therefore, repletion may be necessary before a loop diuretic is effective.

The use of saline as an irrigant results in volume overload and volume expansion without hypernatremia. A diuretic and fluid restriction are therapeutic.

On occasion ammonium intoxication may occur with the use of glycine.

Prevention of untoward long-term sequelae is best accomplished by recognition of the potential problems and correcting the metabolic abnormalities early, even though they may be of minor degree.

Prevention of Surgical Site Infection

The NNIS guidelines recommend preoperative prophylactic antimicrobial therapy for procedures
with an estimated SSI risk >1% based upon the NNIS score.

Prophylactic antimicrobial therapy should be strongly considered for:
(i) any clean-contaminated procedure,
(ii) any clean procedure in a patient with an NNIS score >1
(iii) an immunocompromisedpatient,
(iv) when any prosthetic material is inserted,
(v) when the operative area contains high bacterial counts, such as the axilla or scrotum.

NNIS Score Risk of SSI (%)
0: 1.5
1: 2.9
2: 6.8
3: 13.0

Note: Because it is difficult to estimate an individual patients risk of SSI based on traditional risk factors
the NNIS score was developed to consider the interaction between multiple
risk factors and provide individualized SSI risk assessments. Estimates are based on over 84,000
procedures with 2376 documented SSIs. To calculate NNIS score, contaminated and dirty wounds are
given 1 point, an ASA score of III or greater is given 1 point, and length of procedure >75th percentile
is given 1 point.
Abbreviations: NNIS, National Nosocomial Infection Surveillance System; SSI, surgical site infection.

Timing of antimicrobial prophylaxis administration is critical. A large study by Stone et al. found that the lowest SSI risk occurred when therapy was initiated within one hour of surgery.
Patients who received therapy after the incision had nearly the same risk as patients who
did not receive prophylaxis. More recent data corroborate the conclusion that timely preoperative
antimicrobial administration can reduce SSI rates. These and other observations
demonstrate the importance of obtaining therapeutic serum antimicrobial levels before the surgical
incision and exposure to bacteria.

Current guidelines suggest that prophylactic antimicrobials should be redosed appropriately for lengthy procedures and should stop within 24 hours of surgery.

Recent data support prophylactic antimicrobial therapy for trans-scrotal surgery based on
high bacterial counts on the scrotum and perineum. In a retrospective review of 131 outpatient
scrotal procedures, Kiddoo et al. found a 9.3% overall SSI rate among patients who did not receive
prophylactic therapy. In contrast, Swartz et al. found a 4% SSI rate in over 100 trans-scrotal procedures with a mean follow-up of 36 months (Swartz M, Urology, University of Washington).
Although the precise benefit of prophylactic antimicrobials cannot be ascertained by comparing
such retrospective studies, these data do suggest that scrotal wounds merit consideration as
clean-contaminated wounds that may warrant prophylaxis.

Prophylactic antimicrobial agents should be selected based on the most likely organisms
encountered. Beta-lactam antibiotics, such as the cephalosporins, are the most common agents
used for prophylaxis.
Recommendations include cefazolin for clean abdominal procedures or cefotetan for clean-contaminated abdominal procedures involving the gastrointestinal tract.
Clindamycin or vancomycin regimens are recommended alternatives for patients with
documented beta-lactam allergies. Other possible regimens include combinations of either
metronidazole or clindamycin with gentamicin or a floroquinolone. Currently, there is no
evidence supporting the use of prophylactic vancomycin rather than other agents, even in hospitals with perceived high rates of bacterial resistance.

Recommendations for specific urologic procedures are described next
Special consideration must be given to preventing bacteremia in surgical patients with
prosthetic joints who are at risk for joint infections or patients with certain cardiac anomalies
who are at risk for life-threatening endocarditis. The American Urological Association (AUA)
and the American Heart Association (AHA) have published specific guidelines for antibiotic
prophylaxis in these patient populations (as outlined previously).

Transient bacteremia can occur after a variety of urologic procedures, especially if patients
are instrumented during active UTI. Identification and treatment of active infections is strongly
recommended prior to any elective procedure. Bacteremia is commonly associated with urologic
procedures, with rates of 31% for patients undergoing TURP, 24% among patients undergoing
urethral dilations, 44% in patients having prostate needle biopsy, and 7% in patients having
office urodynamics. The AHA recommends endocarditis prophylaxis for patients undergoing prostatic surgery, urethral dilations, cystoscopy, or ureteroscopy.

Prophylaxis is not necessary for urethral catheterization or circumcision in the absence of clinical infections.

Perioperative ampicillin or vancomycin with gentamicin is recommended for high-risk patients while moderate-risk patients can be treated with single-agent ampicillin or vancomycin. High risk patients are defined by having prosthetic heart valves, previous histories of endocarditis, or complex congenital anomalies. Currently, the AUA recommends assessing patients overall risk for artificial joint infection based on a combination of patient-related and procedure-related factors.


Urosepsis is a syndrome resulting from a complicated UTI in a patient with one or more of the following signs: tachypnea, tachycardia, hyperthermia or hypothermia, or evidence of inadequate end-organ perfusion.

Inadequate tissue perfusion is often accompanied by elevated plasma lactate, oliguria, or hypoxemia.

Septic shock refers to sepsis syndrome that is accompanied by hypotension. Septic shock is a rare event after urologic procedures. Fortunately, septic shock following urologic procedures (often termed urosepsis) has a more favorable prognosis than septic shock from diseases of other organ systems because many urologic disorders are correctable. After correction of underlying urologic factors, the pathophysiology
of urosepsis is often reversible.

Thursday, September 27, 2012

Prune belly syndrome

Abdominal distension and prominent wrinkling of the abdominal skin are characteristic of prune belly syndrome. Although the underlying pathophysiology is enigmatic, distension of the abdomen associated with distension of the urinary bladder is present in all cases. (From MacLennan GT, Cheng L: Atlas of Genitourinary Pathology. London, Springer-Verlag, 2011.)

In the classic form of prune belly syndrome, the bladder appears distended, and there is bilateral hydroureteronephrosis. It is unclear whether failure of bladder emptying is a mechanical or a physiologic problem. Mechanical obstructions may include posterior urethral valves, urethral diaphragm, urethral stenosis, atresia or multiple lumina; or the bladder neck may be incompetent, forming a flap-like valve. When seen at autopsy, the bladder is not always massively distended and thin-walled. After decompression, it may be small or normal-sized but markedly thick-walled; in such cases, bilateral upper tract distension and renal abnormalities are readily apparent nonetheless. (From MacLennan GT, Cheng L: Atlas of Genitourinary Pathology. London, Springer-Verlag, 2011.)

Wednesday, September 26, 2012

Renal Cell Carcinoma - A Reappraisal part 9


RCC is a common malignancy with an incidence that has risen over the last 30 years largely due to incidental findings on imaging. During this time, the evaluation and management of RCC has evolved due to a greater understanding of the genetics of the disease, changes in the TNM staging system, and a trend to less invasive and organ-sparing surgical treatments. Minimally invasive procedures will continue to be at the forefront of treatment in the decades to come. With the advent of biologic response modifiers, additional therapies are now available for patients with metastatic RCC. Nurses and physicians caring for patients with RCC must be knowledgeable about these newer treatment modalities, which patients are appropriate candidates for such therapies, anticipated response rates, and the management of potential adverse effects. A multidisciplinary approach, which includes nurses and allied personnel, will continue to be vital in the management of these patients.

Renal Cell Carcinoma - A Reappraisal part 8

Treatment Options for Stage IV Disease

The value of nephrectomy in metastatic RCC has long been debated. For Stage IV disease, surgery may be considered in carefully selected patients. Cytoreductive nephrectomy can be considered for palliation of local symptoms before initiating systemic immunotherapy. Two welldesigned randomized-controlled trials comparing immuno therapy alone versus immuno therapy and radical nephrectomy showed increased survival in the combined group (Flanigan et al., 2001; Mickisch, Garin, von Poppel, de Prijck, & Sylvester, 2001). Reports have documented regression of metastatic RCC after removal of the primary tumor; however, this is extremely uncommon (Marcus et al., 1993).
Removal of a solitary metastasis is indicated in select patients with good overall performance status. A retrospective analysis from a single institution revealed improved cancer-specific survival advantage, even with removal of more than one metastatic lesion. The authors also reported increased risk of death due to RCC in patients who did not undergo surgical resection of metastasis (Alt et al., 2011). This area is still under great debate, and more studies are needed.
Paraneoplastic syndromes in RCC include hypercalcemia, polycythemia, galactorrhea, anemia, nonmetastatic hepatic dysfunction (Stauffer's syndrome), hypertension, Cushing's syndrome, altered glucose metabolism, amyloidosis, neuromyopathies, vasculopathies, nephropathies, and prostaglandin elevation (Palapattu, Kristo, & Rajfer, 2002). Palliative nephrectomy can be considered in patients with metastatic disease for alleviation of symptoms, such as pain, hemorrhage, malaise, hypercalcemia, erythrocytosis, or hypertension, but many clinicians believe most symptoms can be treated medically without surgical intervention.
Biological therapies include interferons, interleukins, colonystimulating factors, monoclonal antibodies, vaccine gene therapy, and non-specific immunomodulators. Interferons are natural glycoproteins with antiviral, antiproliferative, and immunomodulatory properties. Interleukin-2 (IL-2) is a T-cell growth factor and activator of T cells, as well as a natural killer cell. IL-2 affects tumor growth by activating lymphoid cells in vivo without directly affecting tumor proliferation. Interferons and interleukins are cytokines with low response rates (5% to 20%); a median overall survival is approximately 12 months (Fisher, Rosenberg, & Fyfe, 2000; Janzen, Kim, Figlin, & Belldegrun, 2003; McDermott et al., 2005).
Immunomodulators, such as lenalidomide, a derivative of thalidomide, inhibits vascular endo thelial growth factor (VEGF), stimulates T and natural killer cells and inhibits inflammatory cytokines. Currently in phase 2 trials, this drug showed an antitumor effect in selective cases (Choueiri et al., 2006; Patel et al., 2008). Vaccine trials are still being developed, and autologous vaccine therapy is now being tried in combination with cytokine therapy. Rahma et al. (2010) carried out a pilot clinical trial testing mutant von Hippel-Lindau peptide as a novel immune therapy in metastatic RCC.
More recent developments have focused on targeted cancer therapies (see Table 6). 

Table 6. Biological Response Modifiers
Temsirolimus (Torisel®)
Sunitinib (Sutent®)
Everolimus (Afinitor®)
Sorafenib (Nexavar®)
Pazopanib (Votrient®)
Mechanism of Action
Mammalian target of rapamycin (mTOR) inhibitor. Torisel binds to an intracellular protein FKB12, and the protein drug complex inhibits the activity of mTOR that controls cell division. Inhibitor of mTOR prevents transcription of mRNAs and translational proteins required for cell cycle progression from G1 to S phase.
A kinase inhibitor.
A kinase inhibitor; indicated for patients with advanced RCC after failure of Rx with sunitinib or sorafenib.
A tyrosine protein kinase inhibitor; targets the Raf/Mek/Erk pathway (MAP kinase pathway).
A selective multitargeted tyrosine kinase inhibitor (TK-1), it specifically targets growth factors associated with angiogenesis and tumor cell proliferation.
25 mg IV infusion over a 30-to 60-minute period once/week. Rx continues until disease progression or significant toxicity.
Prophylaxis with IV diphenhydramine 25 to 50 mg approximately 30 minutes before each dose of Torisel.
Starting dose is 50 mg qd for a schedule of 4 weeks of treatment followed by 2 weeks off treatment. Can be taken with or without food. Dose interruption and/or dose modifications in 12.5 mg increments or decrements based on individual safety and tolerability.
10 mg po qd with or without food. Treatment interruption and/or decrease dose to 5 mg may be needed to manage AEs.
400 mg (two 200 mg tabs) po BID. May change to 400 mg qd or qod if significant AEs.
800 mg (4x200 mg tablets) qd. Monitor serum liver tests before start of treatment and once every 4 weeks for at least first 4 months of Rx.
49% increase in median overall survival with Torisel (10.9 months; range: 8.6 to 12.7 months) compared with interferon alpha (7.3 months; range – 6.1 to 8.8 months).
In 2 trials, evaluation efficacy in patients with cytokine refractory mRCC, objective response rates in 34% and 36% treated with Sutent.
Superior to PBO for progression-free survival 4.9 months (range – 4 to 5.5 months) for Afinitor compared with 1.9 months (range – 1.8 to 1.9 months) for PBO
In a study of patients with mRCC randomized to PBO or sorafenib, the progression-free rate was significantly higher with sorafenib (50%) compared with PBO (18%), and the progression-free survival significantly longer for sorafenib (163 days) than placebo (41 days).
In all patients, there was a 9.2 months overall median progression free survival with Votrient use for two months. In treatment naïve (non-prior systemic therapy) patients, it was 11 months.
Adverse Effects
Hyperglycemia, hyperlipidemia, iummnosuppression, interstitial lung disease, rash, asthenia, mucositis, nausea, edema, anorexia.
Fatigue, asthenia, diarrhea, nausea, mucositis, stomatitis, vomiting, dyspepsia, abdominal pain, constipation, headache, rash, hand-foot syndrome, skin discoloration, altered taste, anorexia, bleeding.
Stomatitis, infections, asthenia, fatigue, cough, diarrhea.
Diarrhea, rash/desquamation, fatigue, hand-foot syndrome, skin reaction, alopecia, NV.
Transaminase elevations, QT prolongation and Torsade de Pointes, hemorrhagic events, arterial thrombotic events, GI perforation and fistula, HTN, hypothyroidism, proteinuria, diarrhea, hair color changes, nausea, anorexia and vomiting
Caution when using with potent CYP3A4 inducers and inhibitors.
CYP3A4 inhibitors may increase Sutent plasma concentration; therefore, dose reduction to a minimum of 37.5 mg. CYP3A4 inducers, such as rifampin, may decrease Sutent concentration; therefore, increase dose to a max of 87.5 mg recommended; LV ejection fraction decreases to below lower limits of normal.
For patients with children – Pugh class B hepatic impairment, decrease dose to 5 mg qd; if strong inducers of CYP3A4, increase dose in 5 mg increments to max of 20 mg qd; due to significant increase in exposure, co-administration with strong or moderate CYP3A4 inhibitor should be avoided.
When used concomitantly with Docetaxel, doxorubicin, or fluorouracil increases area under the curve of these agents; CYP3A4 inducers increase metabolism of sorafenib and decrease sorafenib concentrations.
CYP2B6 and CYP2C8 substrates: caution; systemic exposure is expected to increase with co-administration of sorafenib.
Drug interactions – avoid use of strong CYP3A4 inhibitors, caution with CYP3A4 inducers. Caution with patients at higher risk of developing QT interval prolongation and in patients taking anti-arrythmics. Use with caution in patients with hepatic impairment.
Notes: AE = adverse events, CYP3A4 = cytochrome P4503A4, DDi = drug-drug interactions, LV = left ventricle, mRCC = metastatic renal cell carcinoma, PBO = placebo, Rx = treatment, qd = daily, BID = twice a day, QOD = every other day, NV = nausea/vomiting, GI = gastrointestional, HTN = hypertension.
Source: Adapted from Ellsworth, 2011.

Targeted cancer therapies are drugs or other substances that block the growth and spread of cancer by interfering with specific molecules involved in tumor growth and progression (everolimus, sorafenib tosylate, sunitinib maleate, temsirolimus). Pazopanib (Votrient®) is an oral medication that interferes with angiogenesis. It is a kinase inhibitor indicated for treatment of patients with advanced RCC (Kidney Cancer Assoication, 2012). Several targeted therapies have been approved for the treatment of metastatic RCC. One newer form of therapy under investigation is low intensity stem cell transplantation with multiple lymphocyte infusions to treat advanced RCC (NCI, 2012).
Although these therapies are more commonly administered by oncologists, an awareness of these agents by nursing staff and urologists is helpful. Patients with advanced disease are often followed by both urologists and oncologists, and an understanding of the indications and contraindications for use, as well as method of administration and potential adverse effects, may allow urologists and nurses to alleviate some anxieties of patients with metastatic and/or unresectable disease. Urologists and their nursing staff can also provide these patients with basic information that will better prepare the patient for his or her meeting with the oncologist. Finaly, since management of advanced RCC involves a multidisciplinary approach, questions pertinent to therapy may arise in the urologist's office, and thus, an awareness of these agents may allow the urologist and/or urology nurse to address some of the patient's questions.

Renal Cell Carcinoma - A Reappraisal part 7

Treatment Modalities

The treatment options for RCC are surgery, radiation therapy (palliative), targeted therapy (bevacizumab, sumitinib, sorafenib, everolimus, temsirolimus), biological therapy (immunotherapy), and combinations of these (Campbell & Lane, 2012). Surgical resection can be curative in patients who present with localized RCC. Unfortunately, most RCCs are asymptomatic for most of their natural history. Therefore, the diagnosis is frequently made when the disease has progressed locally to the extent where it cannot be resected or has already metastasized.
Historically, radical nephrectomy (removal of kidney, ipsilateral adrenal gland, and Gerota's fascia) was advocated for the surgical treatment of RCC. Nephronsparing surgery was indicated for those with a solitary kidney, those at risk for inheritable forms of RCC (such as VHL), or patients with baseline or at risk for renal insufficiency (such as with diabetes mellitus). However, the current trend is to consider nephron-sparing surgical procedures when the lesion is amenable.
The role of adrenalectomy at the time of nephrectomy has also been questioned. In a review of 351 patients who underwent radical nephrectomy from 1998 to 2008, Tsui et al. (2000) concluded that adrenal involvement is not likely with localized early stage RCC, and thus, adrenalectomy is not necessary, particularly when the CT scan is negative. In patients with large and upper pole tumors, the risk of adrenal involvement is greater, and ipsilateral adrenalectomy should be performed; all 10 patients with ipsilateral adrenal metastases in the aforementioned review had upper pole tumors (8) and/or large renal masses (2) (Tsui et al., 2000).
For patients with Stage I or Stage II disease, surgery is usually curative. Surgical options include either a radical or partial nephrectomy for T1 (≤ 7 cm) lesions. Recently, there has been a paradigm shift in the treatment of such tumors from radical nephrectomies to more nephronsparing approaches. Numerous studies have shown that patients who have small tumors (< 4 cm) with a healthy contralateral kidney treated with partial nephrectomy will have much higher likelihood of maintaining an acceptable glomerular filtration rate (GFR) over 45 ml/minute when compared to radical nephrectomy patients (36% vs. 5%) (Huang et al., 2006). Survival was better for patients undergoing partial nephrectomy compared to patients treated with radical nephrectomy (85% vs. 78%) for tumors between 4 to 7 cm (p = 0.01). This increased survival is likely attributable to better renal function in patients with partial nephrectomy (Weight et al., 2010).
Other nephron-sparing approaches, such as radiofrequency ablation, cryoablation, and even active surveillance, may be acceptable alternatives to radical nephrectomy for carefully selected patients who are compliant with regular follow-up visits. For patients with Stage III (> 7 cm) primary lesions, however, radical nephrectomy is the standard of care. Guidelines developed by an AUA panel exist for the management of the clinical Stage 1 renal mass (AUA, 2009).
Laparoscopic nephrectomy, hand-assisted laparoscopic nephrec tomy, and robotic-assisted nephrectomy are less invasive procedures than the traditional open radical nephrectomy and are reasonable alternatives to open radical nephrectomy in T1 and T2 tumors. These procedures incur less morbidity, and are associated with less blood loss and a shorter recovery time (Burgess et al., 2007). Disadvantages include higher costs along with the technically demanding aspect of these procedures. Partial nephrectomy is traditionally performed in an open fashion. However, in an attempt to decrease the associated morbidity, this surgery is increasingly being performed laparoscopically or with robotic-assisted laparoscopy by skilled surgeons.
Patients faced with treatment choices regarding management of RCC look to the urologist and urology staff for guidance in selecting the most appropriate treatment. The patient and his or her family may have questions after the initial office visit that can often be addressed in a timely fashion by a knowledgeable nurse. This often decreases the patient's anxiety and allows the patient to further understand recommendations made by the urologist. Informed choice is important, and nursing staff play a critical role in ensuring that the patient understands the information being presented and the risks and benefits of the treatment selected.

Renal Cell Carcinoma - A Reappraisal part 6


High-quality computed tomography (CT) scan both prior to and following administration of intravenous contrast remains the radiologic modality for choice to work up a renal mass. Magnetic resonance imaging (MRI) may be useful in the setting of locally advanced disease, venous involvement, renal insufficiency, or allergy to IV contrast. However, due to concerns related to a potential link between nephrogenic systemic fibrosis (NSF) and gadolinium exposure, routine use of MRI is not advocated, and MRI should be reserved for patients who have had a previous allergic reaction to contrast (American Urological Association [AUA], 2009). Color flow Doppler imaging may be useful in detecting renal vein/vena cava involvement. Metastatic evaluation includes CT of the abdomen and pelvis, chest X-ray, and liver function tests. If chest xray is abnormal, then a CT of the chest is warranted. Bone scan should be ordered if there is an elevation of alkaline phosphatase and/or bone pain (Seaman, Goluboff, Ross, & Sawczuk, 1996).
The role of biopsy for localized renal tumor has evolved. Initially, renal biopsy was believed to offer no significant benefit except in patients with metastases in which a diagnosis was needed. However, more recently, the role of renal biopsy has been re-examined. This is supported by the fact that about 20% of clinical Stage 1 renal masses may be benign, and improvements in accuracy and safety of biopsy, related to better CT and MRI-guided techniques, have resulted in a reconsideration of the role of biopsy (Kummerlin et al., 2008; Lane et al., 2007; Lebret et al., 2007; Oda et al., 2001; Pahernik, Ziegler, Roos, Melchior, & Thuroff, 2007; Remzi et al., 2006; Salamanca et al., 2007; Schmidbauer et al., 2008; Somani et al., 2007; Volpe et al., 2007; Zagoria, Gasser, Leyendecker, Bechtold, & Dyer, 2007). In a review of the pathology and radiology databases of a single tertiary referral from 2000 to 2009, Ramsey and colleagues (2010) suggested that renal biopsy is no longer simply for diagnostic dilemmas in patients with renal masses. Older adult patients under consideration for targeted therapies and unfit for cytoreductive nephrectomy have established a role for renal biopsy in confirming the diagnosis prior to treatment (Ramsey et al., 2010).

Renal Cell Carcinoma - A Reappraisal part 5

Classification, Grading, and Staging

Recent advancements in the understanding of the genetics of RCC have led to a new pathological classification of five different subtypes of RCCs: clear cell, papillary, chromophobe, collecting duct carcinoma (Bellini Duct tumor), and renal carcinoma unclassified (renal medullary carcinoma). This classification is primarily based on cytologic appearance and the cell origin in combination with growth pattern and genetic alterations (Campbell & Lane, 2012; Kennedy et al., 1990).
The grading of RCC is based on the morphology of a neoplasm with hematoxylin and eosin (H&E) staining on microscopy. The most popular and widely used system for grading RCC is a nuclear grading system described by Fuhrman, Lasky, and Limas in 1982. This system categorizes RCC into one of four grades based on nuclear characteristics and has been shown to correlate with prognosis (see Table 3).
Table 3. Fuhrman Grading System
Grade 1
Nuclei of the tumor cells are small (< 10 μm), hyperchromatic, and round (resembling mature lymphocytes), with no visible nucleoli and little detail in the chromatin.
Grade 2
Nuclei of the tumor cells are slightly larger (15 μm) with finely granular "open" chromatin but small, inconspicuous nucleoli.
Grade 3
Nuclei of the tumor cells are larger (20 μm in size) and may be oval in shape, with coarsely granular chromatin. The nucleoli are easily recognizable.
Grade 4
The nuclei are pleomorphic with open chromatin or hyperchromatic and single or multiple macronucleoli.
Source: Fuhrman et al., 1982.

The Tumor Node Metastasis (TNM) staging system is used for staging all histologic variants of renal carcinoma. This system assesses the anatomic extent of disease and has been shown to correlate with prognosis. A revision was proposed in 2010 and is supported by the American Joint Committee on Cancer (AJCC) (2010) (see Table 4).
Table 4. Tumor Node Metastasis
Tumor (T) Description
Primary tumor cannot be assessed
No evidence of primary tumor
Tumor 7 cm or less, limited to kidney
Tumor 4 cm or less in greatest dimension, limited to the kidney
Tumor more than 4 cm but not more than 7 cm in greatest dimen-sion, and limited to the kidney
Tumor greater than 7 cm, limited to kidney
Tumor more than 7 cm but less than or equal to 10 cm in greatest dimension, limited to the kidney
Tumor more than 10 cm, limited to the kidney
Tumor extends into major veins/adrenal/perinephric tissue; not beyond Gerota's fascia
Tumor invades perinephric tissue, renal sinus or renal vein
Tumor extends into renal vein(s) or vena cava below diaphragm
Tumor extends into vena cava above diaphragm or into wall of vane cava at any level
Tumor invades beyond Gerota's fascia or directly into adrenal gland
Regional lymph nodes
Regional nodes cannot be assessed
No regional lymph node metastasis
Metastasis in a single regional lymph node
Metastasis in more than one regional lymph node
Distant metastasis
Distant metastasis cannot be assessed
No distant metastasis
Distant metastasis
Source: Edge et al., 2010.

Another commonly used staging system ranges from Stage I to IV based on anatomic stage and places into a prognostic group (see Table 5).
Table 5. Anatomic Staging System/Prognostic Group
Anatomic Stage
Prognostic Group
Stage 1
T1 N0 M0
Stage 2
T2 N0 M0
Stage 3
T1 or T2, N1 M0
T3 N0 or N1, M0
Stage 4
T4 any N M0
Any T, any N, M1
Source: Edge et al., 2010.

It is hoped that with greater knowledge of tumor genetics and immunohistochemistry, there will be an improved ability to make prognoses and appropriately target therapy to those who would most benefit (Odonez & Hank, 2011).

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