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Biomedical subjects

Rodney Davis

Publications and source records attributed to Rodney Davis.

18 recordsLinked to original sources

Transperitoneal versus extraperitoneal robotic-assisted radical prostatectomy: is one better than the other?

OBJECTIVES: To evaluate the differences, if any, in outcomes with transperitoneal (TP) versus extraperitoneal (EP) approaches during robotic-assisted radical prostatectomy (RARP). METHODS: We reviewed the data from 40 consecutive patients who underwent EP-RARP at our institution by the same surgical team. The outcomes were compared with those of 40 consecutive patients who underwent TP-RARP performed by the same team in a nonrandomized manner. The operative and postoperative parameters (total operative time, estimated blood loss, length of stay, robotic console time, and robotic anastomosis time), as well as complications and surgical margin status, were analyzed and compared. RESULTS: The patient demographics were similar in both groups. Nerve sparing was performed in 35 and 36 patients in the TP and EP groups, respectively. Pelvic lymphadenectomy was performed in 14 and 12 patients in the TP and EP groups, respectively. The operative time was slightly longer with the TP approach at 236 minutes (range 111 to 360) compared with 229 minutes (range 143 to 382) in the EP group, but the difference was not statistically significant (P = 0.5722) between the two groups. Also, the differences in robot console time, anastomosis time, estimated blood loss, and length of stay were not statistically significant between the two groups at the 5% significance level. The complication and positive surgical margin rates were similar in both groups. CONCLUSIONS: As expected, the EP approach is feasible with RARP. Our data suggest that the EP approach is comparable to the TP approach and produces favorable outcomes. Surgeon preference will likely play a significant role in the approach used.

Aged↗

Met-Independent Hepatocyte Growth Factor-mediated regulation of cell adhesion in human prostate cancer cells.

BACKGROUND: Prostate cancer cells communicate reciprocally with the stromal cells surrounding them, inside the prostate, and after metastasis, within the bone. Each tissue secretes factors for interpretation by the other. One stromally-derived factor, Hepatocyte Growth Factor (HGF), was found twenty years ago to regulate invasion and growth of carcinoma cells. Working with the LNCaP prostate cancer progression model, we found that these cells could respond to HGF stimulation, even in the absence of Met, the only known HGF receptor. The new HGF binding partner we find on the cell surface may help to clarify conflicts in the past literature about Met expression and HGF response in cancer cells. METHODS: We searched for Met or any HGF binding partner on the cells of the PC3 and LNCaP prostate cancer cell models, using HGF immobilized on agarose beads. By using mass spectrometry analyses and sequencing we have identified nucleolin protein as a novel HGF binding partner. Antibodies against nucleolin (or HGF) were able to ameliorate the stimulatory effects of HGF on met-negative prostate cancer cells. Western blots, RT-PCR, and immunohistochemistry were used to assess nucleolin levels during prostate cancer progression in both LNCaP and PC3 models. RESULTS: We have identified HGF as a major signaling component of prostate stromal-conditioned media (SCM) and have implicated the protein nucleolin in HGF signal reception by the LNCaP model prostate cancer cells. Antibodies that silence either HGF (in SCM) or nucleolin (on the cell surfaces) eliminate the adhesion-stimulatory effects of the SCM. Likewise, addition of purified HGF to control media mimics the action of SCM. C4-2, an LNCaP lineage-derived, androgen-independent human prostate cancer cell line, responds to HGF in a concentration-dependent manner by increasing its adhesion and reducing its migration on laminin substratum. These HGF effects are not due to shifts in the expression levels of laminin-binding integrins, nor can they be linked to expression of the known HGF receptor Met, as neither LNCaP nor clonally-derived C4-2 sub-line contain any detectable Met protein. Even in the absence of Met, small GTPases are activated, linking HGF stimulation to membrane protrusion and integrin activation. Membrane-localized nucelolin levels increase during cancer progression, as modeled by both the PC3 and LNCaP prostate cancer progression cell lines. CONCLUSION: We propose that cell surface localized nucleolin protein may function in these cells as a novel HGF receptor. Membrane localized nucleolin binds heparin-bound growth factors (including HGF) and appears upregulated during prostate cancer progression. Antibodies against nucleolin are able to ameliorate the stimulatory effects of HGF on met-negative prostate cancer cells. HGF-nucleolin interactions could be partially responsible for the complexity of HGF responses and met expression reported in the literature.

Cell Adhesion↗

Positive surgical margins in robotic-assisted radical prostatectomy: impact of learning curve on oncologic outcomes.

OBJECTIVE: The presence of positive surgical margins following radical prostatectomy is a known risk factor for disease recurrence and may lead to adjuvant treatment. Our goal was to assess the incidence of positive surgical margins in our series of robotic-assisted radical prostatectomy (RARP) and its relationship to our learning curve. METHODS: Between February 2003 and August 2005, 140 patients underwent RARP by the same surgical team at our institution. The records of our first 100 consecutive RARPs were retrospectively reviewed. The patients were divided into three groups based on the time of surgery: group I included the first 33 cases; group II included the second 33 cases; and group III comprised the last 34 cases. We compared the incidence and location of positive surgical margins among the groups. Additional variables evaluated included the patient's prostate-specific antigen (PSA) level, preoperative/postoperative Gleason score, clinical/pathologic stage, and pathologic tumour volume. RESULTS: The positive margin rates were 45.4%, 21.2%, and 11.7% for groups I, II, and III, respectively. The difference in positive margin rates in the three groups was statistically significant (p=0.0053). Positive margin rates declined specifically at the apex and bladder neck when comparing the first 33 patients to the last 34 patients. Patient demographics and preoperative staging variables were comparable among all three groups, with no statistically significant differences among them. CONCLUSIONS: This study illustrates that experience gained with time led to a decrease in the incidence of positive surgical margins. We do not feel that a selection bias affected our results because clinical and pathologic staging was evenly distributed within the three study groups. A steady reduction in positive surgical margin rates demonstrates a learning curve, of approximately 30 patients, associated with RARP, and suggests that oncologic outcome is affected by the experience of the robotic surgeon.

Follow-Up Studies↗

Testicular presentation of sarcoidosis and organ preservation: case report and review of management strategies.

We report the case of a 24-year-old Cuban-American man initially presenting with a 1-year history of bilateral testicular pain, subsequently diagnosed as sarcoidosis. The diagnosis was histologically confirmed intraoperatively with excisional biopsy of the right tunica. Genitourinary complaints are a rare initial presentation of this disease. Although therapeutic approaches have varied in published reports, no definitive protocol for treatment has been established. We suggest confirmation of the diagnosis, followed by symptomatic treatment, reserving orchiectomy and steroid therapy for severe, refractory, or disseminated cases.

Adult↗

Prospective evaluation of concomitant lymphadenectomy in robot-assisted radical prostatectomy: preliminary analysis of outcomes.

BACKGROUND AND PURPOSE: Lymph-node staging is important in many patients with prostate cancer, as it influences adjuvant treatment and prognosis. However, lymphadenectomy adds to the operating time, cost, and potential for complications. Herein, we compared the effects of concomitant lymphadenectomy in patients undergoing robot-assisted radical prostatectomy (RARP). PATIENTS AND METHODS: Data were collected prospectively on 145 consecutive RARPs. Patients were evaluated in two groups. Group I was patients who underwent RARP and concomitant lymphadenectomy (LAD)(N = 40), and group II consisted of patients who underwent RARP only (N = 105). Operative time (OT), length of hospital stay (LOS), estimated blood loss (EBL), cost, and complications were compared in the two groups. RESULTS: The mean number of lymph nodes removed per patient in group I was 14.08 (range 9-24). Lymph-node metastases were detected in 2 (5%) of the patients. There were no statistically significant differences in LOS, EBL, OT, operative charges, or hospital charges in the two groups. However, the mean OT increased 9.3% when LAD was performed. At a mean follow-up of 14.8 months (range 3-32 months), 16 complications had been observed in the entire series of patients (11.03%). According to the Clavien system, there were eight grade I complications, seven grade II complications, and one grade III complication. Four complications occurred in group I (10%) and 12 in group II (11.4%). There were no lymphoceles or deep venous thromboses (DVTs) in group I. Cost analysis showed no statistically significant difference between the groups. CONCLUSION: There was no significant impact of concomitant lymphadenectomy on LOS, EBL, charges, or complications when RARP was performed. Although the difference was not statistically significant, the OT will be slightly longer, as an additional procedure is being performed.

Aged↗

Cost analysis of radical retropubic, perineal, and robotic prostatectomy.

BACKGROUND AND PURPOSE: Radical prostatectomy can be performed via a retropubic, perineal, laparoscopic, or robot-assisted laparoscopic approach. Our goal was to evaluate the actual charges incurred at our institution with patients undergoing retropubic prostatectomy (RRP), perineal prostatectomy (RPP), and robot-assisted laparoscopic prostatectomy (RALP). PATIENTS AND METHODS: We retrospectively reviewed all prostatectomy patients treated over a 22-month period (February 2002-December 2004). The case log included 78 RALPs, 16 RRPs, and 16 RPPs. Hospital charges were broken down into operative and nonoperative amounts. Operative times, blood loss, and length of hospital stay were all determined from the patient medical record. The robotic charges were divided further into the initial and final 20 cases. RESULTS: There were significantly higher overall charges for patients undergoing RALP. The operative charges encountered during the robotic "learning curve" were substantially higher than those during our most recent 20 cases. This reduction seemed to correlate directly with the decreasing operative time. The mean operative time for RALP was 262 minutes (range 150-679 minutes). The mean operative time decreased to 225 minutes for our last 20 cases. In contrast, the mean times for RRP and RPP were similar, 202 minutes (range 142-348 minutes) and 196 minutes (range 105-337 minutes), respectively. CONCLUSION: Robot-assisted prostatectomy is associated with substantially higher operative and total hospital charges in addition to the capital expense incurred by the hospital in acquiring and maintaining the robotic system. The operative charges did decrease substantially (27%) once the learning curve had been overcome. Perineal prostatectomy, in experienced hands, remains the most cost-effective procedure, with lower operative costs and shorter times. There was no significant difference in the nonoperative charges in the three treatment groups secondary to the short hospital stay.

Costs and Cost Analysis↗

Robotics in urologic surgery: an evolving new technology.

Rapid technological developments in the past two decades have produced new inventions such as robots and incorporated them into our daily lives. Today, robots perform vital functions in homes, outer space, hospitals and on military instillations. The development of robotic surgery has given hospitals and health care providers a valuable tool that is making a profound impact on highly technical surgical procedures. The field of urology is one area of medicine that has adopted and incorporated robotic surgery into its armamentarium. Innovative robotic urologic surgical applications and techniques are being developed and reported everyday. Increased utilization and development will ultimately fuel the discovery of newer applications of robotic systems in urologic surgery. Herein we provide an overview of the history, development, and applications of robotics in surgery with a focus on urologic surgery.

Equipment Design↗

Laparoscopic partial nephrectomy of solid renal masses without hilar clamping using a monopolar radio frequency device.

PURPOSE: Partial nephrectomy is currently recommended for most amenable solid renal tumors, especially if they are exophytic and less than 4 cm. We reviewed our initial experience with laparoscopic partial nephrectomy for solid renal masses without clamping the renal vasculature using a monopolar device that uses radio frequency energy with low volume saline irrigation for simultaneous blunt dissection, hemostatic sealing and coagulation of the renal parenchyma (TissueLink, TissueLink Medical, Inc., Dover, New Hampshire). MATERIALS AND METHODS: From September 2002 to April 2003, 10 patients underwent transperitoneal laparoscopic partial nephrectomy, including 9 with solid renal masses and 1 with a complex cyst. In all cases the renal hilum was dissected and the renal vessels were isolated but none had renal vascular clamping. The TissueLink DS dissecting sealer or Floating Ball (TissueLink Medical, Inc.) was used to dissect the tumor free bluntly, while simultaneously sealing and coagulating bleeders. RESULTS: Mean patient age was 54.6 years (range 42 to 72). Mean American Society of Anesthesiologists score was 2.3 (range 2 to 4). Mean tumor size was 3.9 cm (range 2.1 to 8). The mass had a peripheral location in 7 cases and a central location in 3. Mean operative time was 232 minutes (range 144 to 280) and mean blood loss was 352 ml (range 20 to 1000). One patient received blood transfusion and all tumor margins were negative. Mean hospital stay was 1.7 days (range 1 to 5) and pain medication use was minimal. One patient had a brief period of urine leakage from the lower pole calix, which was managed successfully by ureteral stenting and Foley catheter drainage of the bladder. CONCLUSIONS: Laparoscopic partial nephrectomy can be performed without renal vascular clamping. TissueLink technology allows complete tumor resection and provides adequate parenchymal hemostasis of the tumor bed. Its scant tissue charring production does not interfere with the pathological assessment of the tumor margin status.

Adult↗

Subjective and objective analysis of the prevalence of Peyronie's disease in a population of men presenting for prostate cancer screening.

PURPOSE: In this study we defined the prevalence of Peyronie's disease in a cohort of men being screened for prostate cancer in the United States. The association between Peyronie's disease, and medical comorbidities and patient self-reported erectile dysfunction was also defined. MATERIALS AND METHODS: A total of 534 men presenting to 1 of 3 prostate cancer screening centers provided a complete medical history, underwent physical examination performed in all by a urologist and completed the Sexual Health Inventory for Men (SHIM) questionnaire. This population was chosen because of the access to a large number of subjects combined with the fact that subjects were not presenting with a specific urological complaint. The diagnosis of Peyronie's disease was based on a palpable penile plaque. Data were assessed using univariate analysis, multivariate logistic regression and Pearson chi-square analysis. RESULTS: A total of 48 patients were found to have a palpable penile plaque on physical examination for a prevalence rate of 8.9%. The mean age of men with Peyronie's disease was 68.2 years compared to a mean of 61.8 years in men without Peyronie's disease (p <0.0001). On univariate analysis hypertension (p = 0.02) and diabetes (p = 0.007) were present with significantly increased frequency in patients with Peyronie's disease. Patients diagnosed with Peyronie's disease had significantly lower values for responses to each of the 5 questions on the SHIM survey. An increase in age and decrease in total SHIM score remained significantly associated with a greater probability of Peyronie's disease on multivariate analysis. CONCLUSIONS: We found the prevalence of Peyronie's disease to be greater than in most previously reported series. We also noted a significant association between Peyronie's disease aging, hypertension, diabetes and self-reported erectile dysfunction.

Adult↗

Periprostatic subendothelial intravascular granulomatosis: a mimic of high-grade intravascular prostatic adenocarcinoma.

A rare case of intravascular granulomatous inflammation mimicking intravascular prostatic adenocarcinoma is reported. To the author's knowledge, there have been no previous reports of prostatic or periprostatic intravascular granulomatous inflammation. A 67-year-old man presented with elevated serum prostate specific antigen (PSA) and was found to have a high-grade adenocarcinoma of the prostate. A radical prostatectomy revealed intravascular subendothelial granulomatous inflammation mimicking vascular invasion of a high-grade adenocarcinoma found elsewhere in the prostate. Immunoperoxidase stains confirmed that the subendothelial infiltrate was composed of histiocytes and not tumor cells. Periprostatic subendothelial intravascular granulomatosis is a rare event, which may mimic vascular involvement of high-grade prostatic adenocarcinoma and may result from a previous needle biopsy of the prostate. Possible mechanisms for this finding are discussed. It is important to distinguish this process from high-grade prostatic adenocarcinoma involving blood vessels for obvious clinical reasons.

Adenocarcinoma↗

Functional androgen receptor confers sensitization of androgen-independent prostate cancer cells to anticancer therapy via caspase activation.

Therapeutic resistance remains an unresolved problem in the clinical management of human prostate cancer (PC). Despite initial positive response to androgen ablation therapy (AAT), virtually all PC patients will relapse due to acquisition of hormone refractory disease and selective outgrowth of tumor cells with multidrug resistance phenotype. We here provide the first experimental evidence that restoring a functional androgen receptor (AR) in the androgen-independent prostate cancer PC3 cells enhances their sensitivity to growth arrest and suppresses their colony-forming ability in response to paclitaxel and gamma-irradiation. Furthermore, functional AR increases the susceptibility of these cells to the apoptotic potentials of therapeutic agents, as evidenced by an increase in caspase activity, annexin V binding, and internucleosomal DNA fragmentation, by inducing caspase activation. The abrogation of the cytotoxic effects by 4-hydroxyflutamide suggests a crucial role for AR activation in enhancing the therapeutic sensitivity of these cells in a ligand-independent fashion. Our data thus demonstrate that a functional AR is a prerequisite for effective therapeutic response and that aberrant expression or blockade by AAT may trigger pathways leading to emergence of PC cells with therapeutic resistance phenotype. Since the mainstay of primary therapy for PC has been AAT by pharmaco-therapeutic or surgical means, this study thus provides a new frontier for revising the AAT therapeutic strategy in conjunction with radiation and/or chemotherapeutic agents.

Androgens↗

Adenovirus-mediated inhibition of NF-kappaB confers chemo-sensitization and apoptosis in prostate cancer cells.

Acquirement of multi-drug resistance by tumor cells represents a major obstacle in the management of prostate cancer. Such resistance was demonstrated in the androgen-independent DU-145 cells in response to paclitaxel and the mechanisms by which these cell develops resistance was not understood. The objective of this study was to examine whether abrogation of the constitutively active NF-kappaB in the chemoresistant, androgen independent DU-145 prostate cancer cells will enhance their sensitivity to cytototoxic agents. Inhibition of NF-kappaB by a dominant negative super-repressor IkappaB mutant adenoviral construct enhanced the apoptotic potentials of paclitaxel and rhTNF-alpha in these cells. Using reporter assays and RT-PCR analysis, we demonstrate that paclitaxel-induced cell death was associated with an increase in NF-kappaB activation and MDR-1 gene expression. Abrogation of these effects by the dominant negative IkappaB adenoviral construct suggests that induction and/or constitutive activation of NF-kappaB can block the paclitaxel-induced apoptotic signaling pathways in this cell line, possibly by increasing the expression of anti-apoptotic and MDR-1 gene products, leading to development of chemoresistance in these cells. We conclude that inhibition of NF-kappaB activation may have therapeutic implications for prostate cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗