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Enlarged Prostate Overview

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Author: Nicolas A Muruve, MD, FRCSC, FACS, Associate Staff, Department of Urology, Cleveland Clinic Florida

Nicolas A Muruve is a member of the following medical societies: American College of Surgeons, American Society of Transplant Surgeons, American Urological Association, and Royal College of Physicians and Surgeons of Canada

Coauthor(s): Keith Steinbecker, MD, Consulting Staff, Department of Urology, St John's Mercy Medical Center; T Brian Willard, MD, Consulting Staff, Department of Surgery, Division of Urology, Lexington Urological Associates

Editors: Allen Donald Seftel, MD, Professor, Department of Urology, Case School of Medicine; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Shlomo Raz, MD, Professor, Department of Surgery, Division of Urology, University of California at Los Angeles School of Medicine; J Stuart Wolf, Jr, MD, FACS, David A Bloom Professor of Urology, Director, Division of Minimally Invasive Urology, Department of Urology, University of Michigan Medical Center; Stephen W Leslie, MD, FACS, Founder and Medical Director of the Lorain Kidney Stone Research Center, Clinical Assistant Professor, Department of Urology, Medical College of Ohio

Author and Editor Disclosure

Synonyms and related keywords: transurethral needle ablation, transurethral needle ablation of the prostate, TUNA, transurethral destruction of prostate tissue by radiofrequency thermotherapy, TUMP, prostate cancer, prostate surgery, prostate-specific antigen, prostate specific antigen, PSA, prostate needle ablation, benign prostatic hypertrophy, benign prostatic hyperplasia, BPH, prostatism, American Urologic Association Symptom Score, AUA Symptom Score, International Prostate Symptom Score, IPSS, prostatic enlargement, enlarged prostate, digital rectal examination, DRE, interstitial radiofrequency needles, interstitial RF needles, heat-induced coagulation necrosis, transurethral resection of the prostate, TURP, TUNA of the prostate, diminished uroflow, urodynamic obstruction



Transurethral needle ablation (TUNA) of the prostate is a procedure used to treat benign prostatic hypertrophy (BPH). It is performed by placing interstitial radiofrequency (RF) needles through the urethra and into the lateral lobes of the prostate, causing heat-induced coagulation necrosis. The tissue is heated to 110°C at an RF power of 456 kHz for approximately 3 minutes per lesion. A coagulation defect is created.

History of the Procedure

Transurethral resection of the prostate (TURP) was originally developed in the United States between 1920 and 1930 and was generally considered the criterion standard for surgical management of BPH.

Recent advances in the surgical treatment of BPH have come via new applications of traditional electrosurgical current. TUNA is one of these new minimally invasive treatments of prostatism. It began as a treatment in the early 1990s, with the first preliminary trials on humans in 1993. The first studies in the United States began in 1994, and the US Food and Drug Administration approved TUNA of the prostate in 1996.

Problem

BPH is a pathologic definition characterized by a cellular proliferation of stromal and epithelial components. The clinical symptoms of BPH are most likely due to the combination of a mass-related increase in urethral resistance and an obstruction-induced and age-induced detrusor dysfunction. Treatment ranges from numerous medical to surgical options. Development and growth of minimally invasive options for BPH have arisen, in part, as a response to the general public's desire for outpatient, less-invasive surgical treatment.

Prostatism describes a clinical syndrome defined as prostatic enlargement, histologic hyperplasia with lower urinary tract symptoms, diminished uroflow, or urodynamic obstruction.

Frequency

No single definition of BPH has gained universal acceptance. Histology, prostate size, symptoms of prostatism, urodynamic measurements, and performance of a prostatectomy are used to define BPH.

Histologically, BPH is characterized by an increased number of epithelial and stromal cells in the periurethral area of the prostate. Prostate size has been used in the past to define BPH, although the relationship between size and lower urinary tract symptoms has not been proven to be linear. Although likely too simplistic, the clinical symptoms of BPH, or prostatism, have been used to define BPH. Urodynamic measurements that show elevated voiding pressures and decreased urine flow also have been used to define BPH. In the past, BPH has also been viewed as an indication for surgery. Although the exact definition is unclear, surgery is indicated based on symptoms, or sequelae of BPH, such as bladder stones or renal insufficiency.

Clinical definitions often include the American Urologic Association (AUA) Symptom Score and the International Prostate Symptom Score (IPSS), which are 2 indices that attempt to define BPH based on its symptoms.

The following table is the AUA Symptom Score. Patient responses to the questions in the table are assigned point values, as follows:

  • Not at all = 0 points
  • Fewer than 1 in 5 = 1 point
  • Less than half the time = 2 points
  • Approximately half the time = 3 points
  • More than half the time = 4 points
  • Almost always = 5 points
Table 1. AUA Symptom Score
Over the past month:Value based on above criteria
How often have you had a sensation of not emptying your bladder completely after you finished urinating?
How often have you had to urinate again less than 2 hours after you finished urinating?
How often have you stopped and started again several times when you urinated?
How often have you found it difficult to postpone urination?
How often have you had a weak urinary stream?
How often have you had to push or strain to begin urination?
Over the last month, how many times did you most typically get up to urinate from the time you went to bed at night until the time you get up in the morning?0 = None
1 = 1 time
2 = 2 times
3 = 3 times
4 = 4 times
5 = 5 or more times

After totaling the scores from the table, the symptoms are assigned the following classifications:

  • 0-7 points – Mild
  • 8-19 points – Moderate
  • 20-35 points – Severe

The IPSS is essentially the same as the AUA Symptom Score.

Using autopsy data, histopathologic evidence of BPH occurs in less than 10% of men aged 40-50 years, 50% of men aged 51-60 years, and 90% of men older than 80 years.

With a clinical diagnosis based on history and a physical examination, the Baltimore Longitudinal Study of Aging diagnosed 69% of men aged 61-70 years with BPH. The Baltimore Longitudinal Study of Aging is a long-term prospective study of normal human aging. It is a National Institute of Health study that was established in 1958 and originally enrolled 1371 men. The subjects are examined every 2 years. Many diagnoses are studied, including BPH. BPH in this study is diagnosed based on clinical judgment, taking into account medical history and digital rectal examination findings.

Regardless of the definition, BPH is an extremely common condition.

Etiology

BPH is characterized by an increased number of epithelial and stromal cells in the periurethral area of the prostate. The increased number of cells is most likely due to epithelial and stromal proliferation or impaired programmed cell death. Other factors may play a role, such as androgens, estrogens, stromal-epithelial interactions, growth factors, and neurotransmitters.

Pathophysiology

Prostatic enlargement leads to an increase in urethral resistance, which then results in secondary bladder changes. Obstruction-related changes in the detrusor function are most likely compounded by age-related changes in bladder and nervous system function. These changes lead to the BPH-related conditions of frequency, urgency, hesitancy, nocturia, and other symptoms.

The TUNA system produces thermal tissue ablation by applying low-level RF energy to prostate tissue. The generated RF is in the form of electrical energy and is delivered by the 2 electrodes, which are in contact with the patient. As the prostate cells resist passage of the current, thermal energy is produced by friction and by the heating of water molecules. This leads to tissue heating and, ultimately, coagulation necrosis. Thermal lesions occur only in a localized area because the RF signal is transmitted into tissue only by direct contact.

Clinical

Patients typically present with worsening symptoms from BPH that begin to affect their quality of life, which are the same symptoms used in the IPSS.

Perform a thorough history and physical examination. The examination should be performed to evaluate for other causes of voiding dysfunction. Multiple aspects of the physical examination might suggest another cause of voiding dysfunction. A general neurologic examination should be performed to assess neurologic function and mental status, motor function, sensory function, and reflexes. Myriad findings may suggest etiologies of dysfunction, from cerebrovascular accident to multiple sclerosis to diabetes mellitus.

Other causes of voiding problems should also be sought in the history and physical examination. For instance, one should evaluate for meatal stenosis or palpable urethral masses. The rectal examination is important to evaluate for prostate nodules or rectal cancers. For patients who require invasive therapy, the digital rectal examination can estimate the size of the prostate. The size of the prostate is important in determining the most appropriate technical approach. However, importantly, note that the size of the prostate does not correlate with the degree of symptoms. Size has not been found to correlate with symptom severity or degree of obstruction after urodynamic evaluation.

Conduct a urinalysis to rule out a urinary tract infection.

Evaluate an obstructive uropathy, if suspected, with a serum creatinine study. It fact, a routine creatine measurement is probably reasonable because distinguishing patients who have obstructive uropathy from patients who do not is difficult. In the authors' practice, a referring physician makes the initial diagnosis in most patients who have renal insufficiency.

Patients with advanced BPH may present with bladder stones or urinary retention.

Conduct uroflowmetry, postvoid residual urine tests, and pressure-flow studies to further evaluate for the possible presence of BPH. These studies are considered optional based on the AUA guidelines for evaluating BPH.

Upper-tract imaging is typically not indicated.

Urethrocystoscopy may be indicated to help select the optimal form of therapy.



Deciding which intervention to choose is difficult. TURP is still considered the criterion standard for surgical intervention. The newer less-invasive treatments are still being evaluated. In general, these treatments are considered less morbid; however, the results are not considered as efficacious or long lasting as the formal TURP. Transurethral needle ablation (TUNA) is offered as one of the less-invasive surgical treatment modalities.

Minimally invasive therapy is generally the next step after failed medical management. This therapy is also the primary therapy for a patient who is not interested in medical therapy and unwilling to undergo a TURP.

Symptoms constitute the primary reason to recommend surgical intervention. This is especially true in light of objective evidence of abnormal function, such as the patient with urodynamic evidence of low peak flow and high residual urine volumes. However, some more absolute indications exist. These are generally considered to be urinary retention, recurrent infection, bladder stones, and azotemia.



No absolute contraindications exist to performing a transurethral needle ablation (TUNA) of the prostate. The relative contraindications are a high bladder neck and large prostate. A large median lobe used to be a contraindication for the procedure, but TUNA is now approved for the treatment of median lobes. In fact, TUNA offers several advantages compared to TURP, as follows:

  • TUNA can be performed in an outpatient or clinic setting with local anesthesia (block of periprostatic nerves) and oral sedation (diazepam [Valium]). Patients are also given a dose of oral meperidine (Demerol) prior to the procedure.
  • The cost is less in terms of the direct cost of the procedure and recovery time, both in and out of the hospital. Naslund and Stitcher estimate that TUNA is 40-50% less expensive than TURP.1 Chapple et al have described other specifics.2 The initial cost of the generator and computer is approximately $16,500. The cost of the disposables range from $1050-$1400 (depending on the volume of cartridges that are ordered). The current global fee is approximately $3500. Of course, those who need further operations also incur those additional costs.
  • A recent cost analysis compared medical therapy with TUNA and found that a 5-year regimen of 5-alpha reductase inhibitor therapy cost the same as TUNA.3 A 5-year regimen of tamsulosin therapy was slightly less expensive. However, combination therapy was found to be more expensive, reaching an equivalent cost to TUNA at 2 years and 7 months.
  • The intraoperative and postoperative morbidity and mortality rates associated with TURP are significantly higher than with TUNA. TUNA is associated with fewer sexual side effects and less bleeding. The anesthetic requirement is also lower. Although more recent data suggest that the long-term outcomes may not be as durable as those achieved with TURP, the decreased associated morbidity makes TUNA a useful treatment option for prostatism in select patients.



Lab Studies

  • In general, no set workup studies have been determined beyond the standard history and physical examination, which are required before transurethral needle ablation (TUNA) can be performed. In fact, one advantage of TUNA (as compared with TURP) is that a general or spinal anesthesia is not required. The most common reason for intervention is symptoms of bladder outlet obstruction and bladder irritability, which interfere with the patient's quality of life. The AUA Symptom Score and the IPSS are indices that attempt to quantify the degree of symptoms. Typically, patients whose symptoms fail to respond to watchful waiting or medical therapy are offered surgical intervention. More absolute indications for intervention include acute urinary retention, recurrent infection, azotemia, and cystolithiasis.
  • Performing a set of chemistries and a CBC count with differential is prudent for the evaluation of a patient's general health. Specifically, evaluate creatinine to assess for obstructive uropathy.
  • One should screen for prostate cancer with a serum prostate-specific antigen (PSA) study and a digital rectal examination.

Imaging Studies

  • No imaging studies are needed.

Other Tests

  • Urodynamics are not necessary, but uroflowmetry, postvoid residual urine volumes, and pressure-flow studies may provide additional information for diagnosis and may offer the chance that a prostatectomy may be beneficial. However, these tests are not uniformly recommended because they are difficult to interpret and the results are often irreproducible.

Diagnostic Procedures

  • No preoperative procedures are necessary. Preoperative transrectal ultrasonography and cystoscopy may be useful to determine the optimal form of surgical treatment. 
    • The fact that the size of the prostate does not correlate with the degree of symptoms is well known. Thus, ultrasonography to evaluate for the size of the prostate would not help in the diagnosis. Also, performing a cystoscopy to evaluate for size would similarly not be helpful in establishing a diagnosis of benign prostatic hypertrophy (BPH). However, in the population of patients in whom invasive treatment is being considered, these tests may be useful because knowing the size and shape of the prostate is helpful in determining which form of treatment may be optimal. Once a decision to proceed with TUNA is made, ultrasonography of the prostate is required to obtain prostate length and width. This is needed to determine the needle length for treatment and helps determine how many lesions are needed for treatment.
    • Generally, the ideal patient for TUNA is thought to be a man with obstructive symptoms and a prostate of 60 g or less with predominantly lateral lobes.
    • Patients found to have larger glands may be offered different forms of treatment. Naslund and Stitcher, however, have done some work with TUNA in these patients, which is discussed in Outcome and Prognosis.1
    • Historically, patients with glands larger than 100 mL are thought to be candidates for open prostatectomies. However, many urologists have gained considerable expertise in safely performing TURP on patients with prostates larger than 100 mL. The decision of which surgical therapy to perform depends, to a large degree, on the individual surgeon's skill and experience with both TURP and open surgery. For those with exceptional skill, expertise, and experience with TURP surgery, open prostatectomy for benign prostatic disease may be rarely required.

Histologic Findings

Histologic studies, mainly derived via transrectal ultrasonography of the prostate and needle biopsy, are needed only in the event of an elevated PSA level or suggestive physical examination to rule out prostate cancer.



Surgical therapy

Prior to starting the procedure, transrectal ultrasonography is performed to determine the length and width of the prostate. The periprostatic block can also be placed at this time. The length helps determine the number of lesions required to appropriately treat the gland. The width is used to determine the needle length.

Place interstitial radiofrequency (RF) needles through the urethra and into the prostatic lateral lobes to cause coagulation necrosis. Heat the tissue to approximately 110°C at an RF power of 456 kHz for approximately 3 minutes per coagulation defect, thereby creating the lesion. Specifically, the area of coagulation necrosis that is created is an ellipsoidal volume along the axis of the needle antenna.

RF energy is created and delivered to the active electrode by the RF generator. The electrode that delivers the RF energy and heats the tissue is the active electrode. It has a very small surface area, allowing the RF current to concentrate in the area immediately surrounding the small electrode.

Externally apply the indifferent electrode, which is large in size. This serves to collect the RF current delivered by the active electrode. No tissue heating occurs near this indifferent (second) electrode. Tissue heating occurs in the concentrated area surrounding the active electrode because this tissue resists the flow of RF current.

At further distances from the active electrode, the RF current rapidly decreases; thus, no further tissue heating occurs and a sphere of coagulation necrosis around the active electrode results.

The size of the lesion is related to the depth of the electrode, the size of the electrode, the power used, and the duration of treatment.

Use a 22F delivery catheter to deliver the RF via 2 needles at 40° angles to each other and at 90° angles to the catheter. The needles are located at the tip of the catheter and are advanced into the prostate by piercing the urethra.

Treat the prostate by moving the RF needle within the various prostatic zones, from the bladder neck to the verumontanum. The number of treatment planes is based on the length of the prostate. Perform approximately 1 plane per 1-1.5 cm of prostatic urethral length (ie, minimum of 2 treatment planes).

The prostatic urethra is preserved. Because the pain-sensitive region of the prostatic urothelium is preserved, general or spinal anesthesia is not needed. Urethra preservation is also thought to reduce postoperative complications of irritative voiding and hematuria.

The needles are covered by insulated sheaths, which allow for control of the length of the exposed needles. Thermosensors on the end of the catheter, in the needle sheaths, and in the rectum measure the temperature in the prostate and periprostatic areas. The shaft of the delivery catheter can be rotated 180°. The RF creates temperatures in the active electrode of 70-110°C, and treatment times are 3 minutes per lesion created.

In the early work on transurethral needle ablation (TUNA), Schulman performed pathologic examinations of the coagulation defect. This area of necrosis ranged from 1.2 cm by 0.7 cm to 1.7 cm by 1 cm.

Importantly, note that the high bladder neck probably should not be treated. Experience with this is very limited. Another drawback is that, with TUNA, no tissue is available for pathologic analysis.

Preoperative details

Most patients are treated with oral sedation (Valium and Demerol) and urethral gel. Local anesthesia is placed with ultrasound or digital guidance. This typically is an outpatient procedure.

The patient needs to have sterile urine prior to performing TUNA. If this is not the case, he should be adequately treated with antibiotics.

Intraoperative details

The procedure lasts approximately 30 minutes. The number of treatments is based on the length of the prostate. For lengths of less than 3 cm, use one treatment plane. For lengths of 3-4 cm, use 2 planes. For lengths greater than 4 cm, use 3 or more planes.

Postoperative details

Postoperatively, the patient typically wears a catheter for 1-3 days. Postoperative urinary retention is reported in 13-41% of patients. Treatment is typically conservative (ie, catheter drainage), and this retention tends to resolve in less than 2 days in most patients. Secondary catheterization is reported in 12% of patients, and most patients are able to return to work in 2-3 days.

Postoperative antibiotic coverage is recommended for 3-5 days after TUNA or after the catheter is removed.

Follow-up

Determining the length of time necessary for the coagulation defect to mature is difficult. Pathologic studies performed at 1 month following TUNA continue to show areas of maturing fibrosis and necrosis. Naslund feels that patients may not see improvement in voiding symptoms for 2-6 weeks.1 Furthermore, the patient may continue to see improvement for up to 2-3 months postoperatively. Therefore, the therapy should not be considered a failure until after 2-3 months.

Some patients fail to resume voiding or fail to see significant improvement in symptoms following TUNA. These patients are typically treated with a formal TURP. Rosario et al reported that 22 out of 71 (31%) men treated with TUNA for symptomatic benign prostatic hypertrophy (BPH) proceeded to a TURP during a 1-year follow-up study.4 Kahn et al, Rodrigo Aliaga et al, Millard et al, and Zlotta et al report performing a TURP following initial treatment with TUNA in 2 of 45 patients (4%), 7 of 42 patients (14%), 5 of 20 patients (25%), and 8 of 38 patients (21%), respectively.5, 6, 7, 8 Thus, a total of 44 patients out of 216 (20%) went on to undergo TURP. Long-term follow-up examinations over a period of months to years are needed to reevaluate symptom improvement.

For excellent patient education resources, visit eMedicine's Prostate Health Center. Also, see eMedicine's patient education article Enlarged Prostate.



Minimally invasive therapy is generally the next step after failed medical management, and it is the primary therapy for a patient who is not interested in medical therapy but is unwilling to undergo TURP. No mortality is reported, and morbidity is low.

Reported rates of urinary retention are 13-42%. Retention appears transient, lasting from 12-48 hours. Postoperative catheter usage alleviates this problem.

Urinary incontinence is not reported.

Macroscopic hematuria is noted in most patients for up to 24-48 hours. This is usually self-limiting and requires no treatment. Ensure that patients with coagulopathies have them corrected prior to transurethral needle ablation (TUNA).

Irritative voiding symptoms occur in up to 40% of the patients; however, these are typically self-limiting and resolve within 7 days. These complaints rarely last beyond 4 weeks.

A urinary tract infection and epididymitis are essentially nonexistent in the face of sterile urine preoperatively and appropriate antibiotic coverage postoperatively. Coverage is recommended for 3-5 days after TUNA or after the catheter is taken out.

Urethral strictures may occur from instrumentation of the urethra. Reported rates are less than 2%; however, reported rates with a standard TURP are as high as 7.3%.

Little evidence suggests that retrograde ejaculation occurs. Marginal decreases in ejaculatory fluid are reported. Reported rates after TURP are 50-95%.

The incidence of erectile dysfunction is rare, less than 2%.

Impotence is reported in approximately 3% of the patients, and deterioration in function is reported slightly more often. Improvement in erectile function is reported by 14-21% of men.

Postoperative hematology and electrolyte changes are not noted in these patients.



Numerous clinical trials have been performed worldwide. Various parameters are used to assess the performance of transurethral needle ablation (TUNA). Subjective improvement ranges from 56-61% at 6 months, 40-70% at 1 year, and 57-73% at 2 years. In a review of more than 10 studies on 546 patients, the overall average improvement was 58% at 1 year, 60% at 2 years, and 66% at 3 years.

Schulman and Zlotta collected data for 2 years from 150 men with symptomatic benign prostatic hypertrophy (BPH).9 They found the following: (1) the peak flow rate (PFR) improved from 9.8 mL/s to 17 mL/s at 1 year and to 16.8 mL/s at 2 years, (2) the mean AUA Symptom Score improved from 21 to 8.8 at 1 year and to 9.2 at 2 years, and (3) the mean postvoid residual urine volume improved from 77 mL to 44 mL at 1 year and to 25 mL at 2 years.

PFRs (Q-max) improved from 28% to 93%. After TURP, the Q-max typically increased more than 100%. In a review of 546 patients, the average improvement was 77% at 1 year, 82% at 2 years, and 92% at 3 years.

Hill et al recently studied the durability of TUNA 5 years after treatment.10 They found that patients treated with TUNA had stable responses over 5 years based on IPSS, quality of life, and PFR. These were all statistically significant at all yearly intervals when compared to baseline. At 5 years, IPSS scores decreased from 24 to 10.7, quality of life improved from 11.8 to 3.8, and PFR improved from 8.8 mL/s to 11.4 mL/s.

In the prospective American study, TURP was randomized against TUNA (see Table 2). In the TURP group, PFRs at 12 months were 20.8 mL/s. In the TUNA group, PFRs were 15 mL/s. Both groups had initial PFRs of 8.8 mL/s. The AUA Symptom Scores improved from 23.9 to 11.1 in the TUNA arm and from 24.1 to 8.3 in the TURP arm.

The decrease in the postvoid residual urine volume after a TUNA procedure is 13-80%. Acceptable evidence does not exist that demonstrates a significant reduction in prostate size. No long-term data beyond 3 years are available.

Few studies exist regarding the efficacy of the TUNA procedure on the treatment of urinary retention secondary to BPH. Zlotta et al reported a success rate of 79% (30 of 38) in patients with retention.8 In addition, Millard et al reported a success rate of 78% (15 of 20) in treating patients with retention.7

Although the ideal use of TUNA has been thought to be in patients with large lateral lobes, Naslund and Stitcher reported that TUNA can be used effectively in patients with large median lobes.1 The key to this form of treatment is to ensure that the needles are in the median lobe and do not protrude into the bladder.

Very limited experience has been gained with TUNA being used to treat patients with high bladder necks. At this time, these patients should probably be treated with another form of therapy.

Table 2. Comparison of TURP and TUNA 

TURPTUNA
Initial peak flow8.8 mL/s8.8 mL/s
Peak flow at 12 mo20.8 mL/s15 mL/s
Improvement in AUA Symptom
Score
From 23.9 to 11.1From 24.1 to 8.3



Expect further advances and refinement of the existing technologies. A further study is needed in order to maximize the usefulness of transurethral needle ablation (TUNA). Without question, TUNA offers the patient a less morbid procedure. The results of TUNA are undeniably promising, yet by no means are they as good as TURP (ie, the criterion standard). The greatest difficulty in evaluating TUNA is determining the durability of its results. Certainly, only time will tell.

At present, the decision to proceed with surgical treatment of benign prostatic hypertrophy (BPH) is difficult. Obviously, the decision is based on the patient's and the surgeon's preferences but comes down to the fact that TUNA is better tolerated, carries fewer adverse effects, and generally offers reasonable results compared with those of TURP. In the authors' opinion, if the patient and the physician are in agreement, these reasons are worth the uncertainty of the long-term results and the possibility of a poorer outcome.



For additional information, visit Medscape’s BPH Resource Center.



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Transurethral Needle Ablation of the Prostate (TUNA) excerpt

Article Last Updated: Feb 7, 2008