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Scott E Eggener

Publications and source records attributed to Scott E Eggener.

At least 19 recordsLinked to original sources
PubMed2007

Pathologic findings and clinical outcome of patients undergoing retroperitoneal lymph node dissection after multiple chemotherapy regimens for metastatic testicular germ cell tumors.

BACKGROUND: Postchemotherapy surgery is an essential component in the management of patients with metastatic germ cell tumors (GCT). The authors assessed their institutional experience of retroperitoneal lymph node dissection (RPLND) after multiple chemotherapy regimens for advanced GCT. METHODS: By analyzing the institutional prospective surgical database from 1989 to 2004, 71 patients were identified who underwent RPLND after multiple chemotherapy regimens. Clinicopathologic and treatment trends were characterized, and predictors of disease-specific survival (DSS) were evaluated. RESULTS: The histologic findings at RPLND were fibrosis in 36 men (51%), GCT in 20 men (28%), and teratoma in 15 men (21%). Patients who underwent RPLND from 1989 to 1998 (n = 47), compared with patients who underwent RPLND from 1999 to 2004 (n = 24) were more likely to have GCT (36% vs 13%; P = .04). Patients who received taxane-containing chemotherapy regimens as salvage therapy had lower rates of GCT at RPLND (14% vs 42%; P = .01), higher rates of fibrosis (63% vs 39%; P = .04), and similar rates of teratoma (31% vs 33%; P = .9). The 5- and 10-year DSS rates were 74% (95% confidence interval [95% CI], 62-86%) and 70% (95% CI, 56-84%), respectively. Five-year DSS based on worst histology of RPLND and extraretroperitoneal specimens was 87% (95% CI, 75-99%) for fibrosis, 87% for teratoma (95% CI, 63-100%), and 47% for GCT (95% CI, 23-71%; P = .004). On multivariable analysis, retroperitoneal mass > or = 5 cm and GCT were predictors of worse DSS (P = .03 and P = .005, respectively). CONCLUSIONS: Taxane-based salvage chemotherapeutic regimens appear to have decreased the rate of GCT at RPLND. The current data support RPLND in select patients after salvage chemotherapy, because a considerable proportion has teratoma or GCT, and the 10-year DSS rate after resection is 70%.

Adolescent↗
PubMed2006

The natural history of noncastrate metastatic prostate cancer after radical prostatectomy.

OBJECTIVES: To characterise the natural history of metastatic prostate cancer after radical prostatectomy (RP) in patients followed expectantly for rising prostate-specific antigen (PSA) (noncastrate metastases). METHODS: Cox proportional hazards analyses were used to assess predictors of survival among 95 patients who developed clinically detectable noncastrate metastases after RP. The initial metastatic phenotype was characterised as minimal (nodal or axial skeletal involvement) or extensive (appendicular skeletal involvement or visceral metastases). Estimates of survival after diagnosis of metastases were generated with the Kaplan-Meier method. RESULTS: Median disease-specific survival from diagnosis of noncastrate metastases was 6.6 yr (95% confidence interval [CI], 5.2, 7.9). The initial site of metastatic disease was bone, lymph node, and viscera in 63%, 36%, and 6% of patients, respectively. Thirteen patients (14%) had extensive disease at their first metastatic manifestation. Longer PSA doubling time in the rising PSA state (hazard ratio [HR] 0.8 for each month increase in doubling time; 95%CI, 0.67-0.94) and the initial metastatic phenotype (HR 0.3 for minimal vs. extensive disease; 95%CI, 0.1-0.6) were associated with improved survival. The prostatectomy Gleason score, lymph node status at RP, PSA level at diagnosis of metastases, and interval from surgery to diagnosis of metastases did not correlate with outcome. CONCLUSION: Men who develop noncastrate metastases after RP may have a durable survival. Favourable prognostic indicators include longer PSA doubling time preceding diagnosis of metastases and initial involvement of axial skeleton or lymph nodes.

Adult↗
PubMed2006

Renal cell carcinoma recurrence after nephrectomy for localized disease: predicting survival from time of recurrence.

PURPOSE: Prognostic factors for patients with metastatic renal cell carcinoma (RCC) are well established. However, the risk profile is unknown for patients with recurrent RCC after a nephrectomy for localized disease. PATIENTS AND METHODS: From January 1989 to July 2005, we identified patients with localized RCC treated by nephrectomy who subsequently developed recurrent disease. We applied a validated prognostic scoring system previously developed for patients with metastatic RCC. Each patient was given a total risk score of 0 to 5, with one point for each of five prognostic variables (recurrence < 12 months after nephrectomy, serum calcium > 10 mg/dL, hemoglobin < lower limit of normal, lactate dehydrogenase > 1.5x upper limit of normal, and Karnofsky performance status < 80%). Patients were categorized into low- (score = 0), intermediate- (score = 1 to 2), and high-risk subgroups (score = 3 to 5). RESULTS: Our final cohort included 118 patients, with a median survival time of 21 months from the time of recurrence. Median follow-up time for survivors was 27 months. Overall survival was strongly associated with risk group category (P < .0001). Low-risk, intermediate-risk, and high-risk criteria were fulfilled in 34%, 50%, and 16% of patients, respectively. Median survival time for low-risk, intermediate-risk, and high-risk patients was 76, 25, and 6 months, respectively. Two-year overall survival rates for low-risk, intermediate-risk, and high-risk patients were 88% (95% CI, 77% to 99%), 51% (95% CI, 37% to 65%), and 11% (95% CI, 0% to 24%), respectively. CONCLUSION: At disease recurrence after nephrectomy for localized disease, a scoring system based on objective clinical and laboratory data provides meaningful risk stratification for both patient counseling and clinical trial entry.

Aged↗
PubMed2006

Enhancement of intermittent androgen ablation by "off-cycle" maintenance with finasteride in LNCaP prostate cancer xenograft model.

BACKGROUND: Intermittent androgen ablation (IAA) was developed with the intention of delaying progression of prostate cancer to androgen-independence and improving quality of life. Our previous studies suggest that relative to dihydrotestosterone (DHT), testosterone (T) is a weak inducer of proliferation and a more potent inducer of differentiation. We hypothesize that administration of finasteride (F), a type-II 5-alpha-reductase inhibitor that increases T and decreases DHT, during the IAA "off-cycle" would enhance the efficacy. METHODS: After LNCaP tumor establishment, nude mice were castrated and randomized to continuous androgen ablation (CAA), continuous androgen ablation plus finasteride (CAA + F), intermittent androgen ablation (IAA), or intermittent androgen ablation plus finasteride (IAA + F). RESULTS: After one cycle of therapy, mice treated with IAA + F had significantly less tumor growth than the other treatment groups (P = 0.002). Mice treated with IAA + F had the best survival (P = 0.048) and were 3-5 times more likely to be alive 70 days following treatment initiation. CONCLUSIONS: IAA with finasteride provides the most favorable tumor growth kinetics and survival compared to both CAA and standard IAA.

Androgens↗
PubMed2006

Safety and efficacy of intravesical bacillus Calmette-Guerin instillations in steroid treated and immunocompromised patients.

PURPOSE: We assessed the safety and efficacy of intravesical bacillus Calmette-Guerin instillations in steroid treated and immunocompromised patients. MATERIALS AND METHODS: We retrospectively reviewed the charts of 697 patients treated with bacillus Calmette-Guerin instillations at our institution from 1991 to 2004. In 24 patients (3.5%) an underlying comorbidity directly affecting the immune system was diagnosed before bacillus Calmette-Guerin administration or steroids were administered at least 6 weeks before and at the time of bacillus Calmette-Guerin instillations. The immunosuppressive effect of steroids was assessed by the percent of lymphocytes. End points were the bacillus Calmette-Guerin response at 6 months, defined as normal cystoscopy, cytology and biopsy when available, and treatment related toxicity. RESULTS: Four patients (17%) had active lymphoma or chronic lymphocytic leukemia during bacillus Calmette-Guerin administration and 21 (88%) had a concurrent condition for which oral steroids (11), inhaled steroids (14) or oral and inhaled steroids (4) were administered. Patients treated with oral steroids had a lower percent of lymphocytes than patients treated with inhaled steroids and 15 age matched patients with high risk superficial bladder cancer and no steroid treatment (12.3% vs 17.5% and 18.6%, respectively). The overall bacillus Calmette-Guerin response rate at 6 months was 58%. Ten of the 24 patients had disease recurrence and 3 had disease progression at a median followup of 63.5 months (IQR 19.5, 89). One patient treated with oral steroids had self-limited febrile disease and worsening of myalgia 48 hours after his third bacillus Calmette-Guerin cycle. No other systemic adverse event following bacillus Calmette-Guerin therapy was recorded and all patients completed scheduled treatments. CONCLUSIONS: Intravesical bacillus Calmette-Guerin is a viable therapeutic option in patients with high risk superficial bladder cancer and concomitant lymphoma or chronic lymphocytic leukemia, treatment with low dose oral steroids or treatment with inhaled steroids. The bacillus Calmette-Guerin response rate at 6 months and the side effects profile associated with bacillus Calmette-Guerin therapy in these patients were comparable to those in patients with no evidence of immunosuppression. Further studies are warranted to assess the safety and efficacy of bacillus Calmette-Guerin instillations in critically immunocompromised patients.

Adjuvants, Immunologic↗
PubMed2006

Prediagnosis prostate specific antigen velocity is associated with risk of prostate cancer progression following brachytherapy and external beam radiation therapy.

PURPOSE: Prostate specific antigen velocity 2.0 ng/ml per year or greater in the year before prostate cancer diagnosis is associated with cancer specific survival following radical prostatectomy and radiation therapy. We evaluated the relationship between prediagnosis prostate specific antigen velocity and cancer progression following primary radiation therapy. MATERIALS AND METHODS: We analyzed the records of 24,893 men from a community based prostate cancer screening study and identified 237 with clinically localized prostate cancer who elected primary radiation therapy. Our final cohort consisted of 130 men, including 83 treated with external beam radiation and 47 treated with brachytherapy. Patient specific variables at diagnosis were analyzed for their value in predicting biochemical progression using American Society for Therapeutic and Radiation Oncology criteria. RESULTS: Mean followup +/- SD was 64 +/- 35 months. Prostate specific antigen at diagnosis, family history of prostate cancer and prediagnosis prostate specific antigen velocity 2.0 ng/ml per year or greater were associated with cancer progression following brachytherapy or external beam radiation. Of men with prostate specific antigen velocity 2.0 ng/ml per year or greater 38% had cancer progression compared to 12% with prostate specific antigen velocity less than 2.0 ng/ml per year (OR 4.3, p = 0.003). The 6-year progression-free survival estimate was 57% in men with prostate specific antigen velocity 2.0 ng/ml per year or greater and 82% in men with prostate specific antigen velocity less than 2.0 ng/ml per year (p < 0.001). On multivariate analysis absolute prostate specific antigen at diagnosis and prostate specific antigen velocity 2.0 ng/ml per year or greater were independently associated with cancer progression in men treated with external beam radiation therapy or brachytherapy. CONCLUSIONS: Men with a prediagnosis prostate specific antigen velocity of 2.0 ng/ml per year or greater are at increased risk for cancer progression following brachytherapy or external beam radiation compared to men with a prostate specific antigen velocity of less than 2.0 ng/ml per year.

Adult↗
PubMed2006

Temporary renal ischemia during nephron sparing surgery is associated with short-term but not long-term impairment in renal function.

PURPOSE: The emergence of laparoscopic nephron sparing surgery has rekindled interest in the impact of warm renal ischemia on renal function. To provide data with which warm renal ischemia can be compared we analyzed short-term and long-term changes in the glomerular filtration rate after temporary cold renal ischemia. MATERIALS AND METHODS: In patients undergoing open nephron sparing surgery the estimated glomerular filtration rate was assessed preoperatively, early in the postoperative hospital stay, and 1 and 12 months after surgery using the abbreviated Modification of Diet in Renal Disease Study equation. We separately analyzed 70 patients with a solitary kidney and 592 with 2 functioning kidneys. The end point was the percent change from the baseline glomerular filtration rate. A linear regression model was used to test the association between the glomerular filtration rate change, and ischemia time, patient age, tumor size, estimated blood loss and intraoperative fluid administration. RESULTS: Median cold ischemia time was 31 minutes in patients with a solitary kidney and 35 minutes in those with 2 kidneys. Compared to patients with 2 kidneys those with a solitary kidney had a significantly lower preoperative estimated glomerular filtration rate (p < 0.001), which decreased a median of 30% during the early postoperative period, and 15% and 32% 1 and 12 months after surgery, respectively. In patients with 2 kidneys the corresponding glomerular filtration rate decreases were 16%, 13% and 14%, respectively. On multivariate analyses in each group cold ischemia duration and intraoperative blood loss were significantly associated with early glomerular filtration rate changes. However, 12 months after surgery age was the only independent predictor of a glomerular filtration rate decrease in patients with 2 kidneys. CONCLUSIONS: Cold renal ischemia during nephron sparing surgery is a significant determinant of the short-term postoperative glomerular filtration rate. Longer clamping time is particularly detrimental in patients with a solitary kidney but it does not appear to influence long-term renal function. Patients of advanced age may be less likely to recover from acute ischemic renal injury.

Aged↗
PubMed2006

Perioperative clinical thromboembolic events after radical or partial nephrectomy.

OBJECTIVES: To evaluate the incidence of, and identify the risk factors for, clinical thromboembolic events after radical/partial nephrectomy. Cancer is an established risk factor for deep vein thrombosis (DVT) and pulmonary embolism (PE); however, their incidence after nephrectomy for renal tumors has been poorly studied. METHODS: We reviewed our prospective institutional renal database and identified 2208 patients who underwent renal tumor surgery from January 1989 to July 2005. The clinical parameters evaluated were age, sex, race, body mass index, smoking history, medical comorbidities, American Society of Anesthesia grade, procedure type, estimated blood loss, and length of hospitalization. Hospital records, discharge "International Classification of Diseases, Ninth Revision" codes, and 30-day postoperative morbidity and mortality data were reviewed to identify patients diagnosed with perioperative DVT or PE. RESULTS: A total of 34 (1.5%, 95% confidence interval 1.1% to 2.1%) thromboembolic events (20 PEs and 14 DVTs) were identified in 33 patients. Patients with a preoperative history of arrhythmia (P = 0.02) or prior DVT (P = 0.053) were more likely to experience PE. The estimated blood loss was directly associated with an increased risk of PE (P = 0.001). Patients with coronary artery disease (P = 0.050) or of advanced age (P = 0.02) were more likely to experience DVT (P = 0.02). CONCLUSIONS: To our knowledge, this is the first study on the incidence of thromboembolic events after nephrectomy. Thromboembolic events are rare but are more likely to occur in patients with coronary artery disease, cardiac arrhythmia, prior DVT, Stage 3 or 4 tumors, or a large estimated blood loss.

Aged↗
PubMed2005

Timing is everything: preclinical evidence supporting simultaneous rather than sequential chemohormonal therapy for prostate cancer.

PURPOSE: Androgen ablation is the mainstay of systemic therapy for prostate cancer, with cytotoxic therapies reserved for hormone-refractory disease. It is not clear, however, that this is the most appropriate sequence of interventions for this disease. This study addresses the ideal timing of systemic treatments in the Shionogi and LNCaP xenograft models. We explored the hypothesis that stress-induced gene expression changes after chemotherapy can induce a hormone-independent phenotype. EXPERIMENTAL DESIGN: Three groups of mice bearing either Shionogi or LNCaP xenografts were treated with (a) initial castration and delayed paclitaxel, (b) initial paclitaxel and delayed castration, or (c) simultaneous castration plus paclitaxel. End points were time to tumor progression and time to sacrifice. Microarray and reverse transcription-PCR analyses were carried out to assess changes in gene expression induced by paclitaxel. RESULTS: Mice receiving simultaneous therapy showed a significant improvement in median time to progression (TTP: Shionogi, 65 versus 38 days, P = 0.004; LNCaP, 105 versus 70 days, P = 0.032) and time to sacrifice (Shionogi, 83 versus 66 days, P < 0.014) versus best sequential therapy. A marked lack of response to castration was observed after initial paclitaxel therapy. Gene expression and reverse transcription-PCR studies confirmed that several genes known to play a role in androgen independence were up-regulated in response to paclitaxel exposure. CONCLUSIONS: In laboratory models of prostate cancer, simultaneous androgen deprivation plus paclitaxel is more effective than sequential treatments. These findings provide preclinical proof-of-principle for ongoing clinical trials addressing the role and timing of systemic therapies in prostate cancer.

Androgens↗
PubMed2005

Preoperative PSA and progression-free survival after radical prostatectomy for Stage T1c disease.

OBJECTIVES: To examine biochemical progression-free survival (PFS) rates as a function of preoperative prostate-specific antigen (PSA) in patients with clinical Stage T1c prostate cancer treated with radical prostatectomy. Controversy exists about whether performing prostate biopsies for PSA levels in the 2.6 to 4.0 ng/mL range provides a PFS advantage compared with detection at higher PSA ranges. METHODS: A total of 2804 men with clinical Stage T1c prostate cancer were treated with radical retropubic prostatectomy and monitored prospectively. The study parameters included preoperative PSA level, pathologic tumor stage, and Gleason grade. Patients were grouped into four clinically relevant strata according to their preoperative PSA level: 2.6 to 4.0, 4.1 to 7.0, 7.1 to 10.0, and greater than 10 ng/mL. The primary outcome was the 10-year actuarial biochemical PFS estimate generated using the Kaplan-Meier method. We compared the strata using the log-rank test. Cancer progression rates were compared using the Cochran Armitage test for trend. The chi-square test was used to compare the pathologic parameters among the PSA strata. RESULTS: Of the men with a preoperative PSA level of 2.6 to 4.0, 4.1 to 7.0, 7.1 to 10.0, and greater than 10.0 ng/mL, 81%, 74%, 72%, and 60%, respectively, had organ-confined disease (P = 0.001) and 23%, 28%, 35%, and 47%, respectively, had a pathologic Gleason grade of 7 or greater (P = 0.001). The corresponding 10-year PFS estimates were 88%, 80%, 76%, and 61% (P = 0.0001, for trend). CONCLUSIONS: Among men with clinical Stage T1c prostate cancer, those with a PSA level of 2.6 to 4.0 ng/mL had the greatest rate of organ-confined disease, lowest pathologic Gleason grade, and greatest 10-year PFS rate.

Adult↗
PubMed2005

Contemporary survival results and the role of radiation therapy in patients with node negative seminal vesicle invasion following radical prostatectomy.

PURPOSE: Seminal vesicle invasion (SVI) in a radical prostatectomy (RRP) specimen is associated with a guarded prognosis. We evaluated patients with SVI treated in the pre-prostate specific antigen (PSA) (1983 to 1991) and PSA (1992 to 2003) eras. MATERIALS AND METHODS: Of patients with prostate cancer treated with RRP from January 1983 through March 2002, 220 with SVI were evaluated, including 67 in the pre-PSA era and 153 in the PSA era. Postoperative PSA greater than 0.2 ng/ml was considered biochemical evidence of cancer progression. Survival rates were compared using Kaplan-Meier estimates to calculate progression-free, cancer specific and all cause survival. Multivariate Cox proportional hazard models were used to correlate variables with disease progression. RESULTS: The incidence of SVI in the PSA era was lower than in the pre-PSA era (6.0% vs 10.2%, p = 0.001). To date 124 patients (56%) have had evidence of cancer progression. The 4 and 7-year progression-free, cancer specific and all cause survival rates were significantly higher in men with SVI in the PSA era (p = 0.02). PSA at diagnosis, cancerous surgical margins and higher Gleason score were significantly associated with progression. Neither adjuvant nor salvage radiotherapy appeared to confer a significant progression-free survival benefit. CONCLUSIONS: The incidence of SVI has decreased in the PSA era. Progression-free, cancer specific and all cause survival rates following RRP in patients with SVI have improved in the PSA era. This may reflect earlier detection in this pathological tumor stage and more favorable prognostic factors associated with PSA screening. Adjuvant radiotherapy does not appear to confer any therapeutic benefit. Salvage radiotherapy can lead to durable PSA regressions in a small percent of men, although no long-term survival advantage can be proved.

Aged↗
PubMed2005

Predictors of subsequent prostate cancer in men with a prostate specific antigen of 2.6 to 4.0 ng/ml and an initially negative biopsy.

PURPOSE: Almost 75% of men with a prostate specific antigen (PSA) of 2.6 to 4.0 ng/ml have no evidence of prostate cancer on biopsy. Deciding whether and when to repeat the biopsy is challenging. We determined if patient specific variables might identify men at increased risk for the subsequent detection of prostate cancer. MATERIALS AND METHODS: We analyzed the records of 24,893 men from a community based prostate cancer screening study. Our study group consisted of 1,202 men with PSA 2.6 to 4.0 ng/ml and a previously negative prostate biopsy. Patient specific variables were analyzed for their value in predicting a future diagnosis of prostate cancer. RESULTS: Of 1,011 men with adequate followup 136 (13.5%) were subsequently diagnosed with prostate cancer. Mean followup +/- SD in men without prostate cancer was 72 +/- 36 months. Prostate cancer was subsequently diagnosed in 35% of men with high grade prostatic intraepithelial neoplasia (HGPIN) on initial biopsy (p <0.0001), in 18% with abnormal or suspicious digital rectal examination (DRE) (p = 0.02) and 16% with an annual PSA velocity of 0 ng/ml (p = 0.002). Multivariate analysis identified HGPIN, initial PSA 3.6 to 4.0 ng/ml, abnormal DRE, family history of prostate cancer and annual PSA velocity 0 ng/ml as predictors of prostate cancer. CONCLUSIONS: Men with a PSA of 2.6 to 4.0 ng/ml and negative biopsy should be advised to undergo repeat biopsy if they have HGPIN, initial PSA 3.6 to 4.0 ng/ml, abnormal DRE, a family history of prostate cancer or a PSA velocity of 0 ng/ml or greater.

Aged↗
PubMed2004

Potency, continence and complications in 3,477 consecutive radical retropubic prostatectomies.

PURPOSE: We report results in a series of 3,477 consecutive patients treated with anatomical nerve sparing radical retropubic prostatectomy (RRP) in terms of recovery of erectile function, urinary continence and postoperative complications. MATERIALS AND METHODS: From May 1983 through February 2003, 1 surgeon (WJC) performed anatomical RRP using a unilateral or bilateral nerve sparing modification when possible. Urinary continence and recovery of erections were evaluated in men with a minimum followup of 18 months. Excluded from potency analysis were men who were not reliably potent before surgery, those who did not undergo a nerve sparing procedure and those who received postoperative adjuvant radiotherapy or hormonal therapy within 18 months of surgery. Other postoperative complications in this patient population were also evaluated. RESULTS: Erections sufficient for intercourse occurred in 76% of preoperatively potent men treated with bilateral (1,770) and 53% of men treated with unilateral or partial nerve sparing (64) surgery. Adequate erectile function was more common following bilateral than unilateral nerve sparing surgery in men younger than 70 years old (78% versus 53%, p = 0.001) compared with those 70 years old or older (52% versus 56%, p = 0.6). Recovery of urinary continence occurred in 93% of all men and was associated with younger age (p = 0.001) but not nerve sparing surgery, tumor stage, prostate specific antigen (PSA), Gleason grade or number of prior prostatectomies performed by the surgeon. Postoperative complications occurred in 320 (9%) of patients and were associated with older age (p <0.0001), nonnerve sparing surgery (p = 0.001), PSA era (p <0.0001) and surgeon experience. Complications were not significantly correlated with clinical stage, pathological stage, preoperative PSA or Gleason grade. There was no perioperative mortality. CONCLUSIONS: Nerve sparing RRP can be performed with favorable potency and urinary continence. Better results are achieved in younger men. Other complications are reduced with increasing surgeon experience.

Aged↗
PubMed2003

The etiology of urolithiasis in HIV infected patients.

PURPOSE: It is commonly thought that urinary lithiasis in HIV infected patients on protease inhibitor therapy is composed primarily of the protease inhibitor itself. Since many HIV infected patients on protease inhibitors presenting to our institution had nonprotease inhibitor stones, we investigated potential underlying metabolic abnormalities that may account for the lithogenesis. MATERIALS AND METHODS: We retrospectively reviewed all HIV infected patients on protease inhibitors with renal colic and evidence of nephrolithiasis who presented to our institution between June 1996 and January 2001. Patients were evaluated for stone composition and metabolic abnormalities of blood and urine when possible. RESULTS: A total of 24 patients were identified, and all were or had been on protease inhibitors (indinavir 14, ritonavir 3, nelfnavir 2, unspecified 5). Of the 14 patients on indinavir only 4 (28.6%) had indinavir containing stones. The remaining stones in this group and in those not on indinavir contained various amounts of calcium oxalate monohydrate and dihydrate, ammonium acid urate and uric acid. Of 10 patients who underwent 24-hour urine collection for metabolic evaluation 8 (80%) had abnormalities, including hypocitraturia in 5, hyperoxaluria in 4, hypomagnesuria in 4, hypercalciuria in 3, increased supersaturation of calcium oxalate in 3 and hyperuricosuria in 2. Abnormalities in the levels of urinary phosphate and sodium were also observed. CONCLUSIONS: HIV infected patients form many types of stones, which probably are attributable to underlying metabolic abnormalities rather than the use of protease inhibitors. A complete metabolic evaluation is warranted in these patients, as a means of guiding treatment to prevent future stone episodes, while avoiding the need to alter antiretroviral regimens.

Adolescent↗
PubMed2003

The p53 tumor suppressor gene and nuclear protein: basic science review and relevance in the management of bladder cancer.

PURPOSE: An extensive body of literature regarding p53 has accumulated during the last 2 decades. The cellular mechanisms of p53 are complex yet well-defined, whereas its clinical usefulness in the management of bladder cancer remains controversial. We outline the basic constitutive functions of p53 and summarize its current role in the management of transitional cell carcinoma of the bladder. MATERIALS AND METHODS: We conducted a MEDLINE based literature review concerning the fundamental mechanisms of p53 and its role in the management of bladder cancer. RESULTS: The p53 gene is a tumor suppressor gene that acts as "guardian of the genome." Many diverse cellular events, including DNA damage and hypoxia, activate the p53 gene. The p53 protein functions as a transcription factor, regulating downstream genes involved in cell cycle arrest, DNA repair and programmed cell death. Loss of p53 function confers genomic instability, impaired apoptosis and diminished cell cycle restraint. Therefore, p53 mutations select for certain critical features of malignancy. Alteration of P53 is the most common mutation in human cancer. Roughly half of all human malignancies, including many urological cancers, exhibit p53 mutations. In bladder cancer p53 mutations have been associated with higher tumor grade and advanced stage, as well as progression of superficial disease to muscle invasion. Moreover, p53 nuclear over expression appears to be an independent predictor of disease progression and decreased survival after cystectomy. CONCLUSIONS: The importance of p53 mutation in tumor cell biology is irrefutable. Wild-type p53 mediates imperative functions such as regulation of the cell cycle and programmed cell death. Deficiency of p53 function by mutation or inactivation abrogates normal cell cycle checkpoints and apoptosis, generating a favorable milieu for genomic instability and carcinogenesis. However, despite the manifest importance of p53 in human malignancy, its current role in the management of bladder cancer appears somewhat limited. A multitude of retrospective studies have associated p53 mutations with adverse outcomes in superficial and muscle invasive disease. Nonetheless, randomized prospective studies are needed to determine the potential clinical implications of p53 in bladder cancer.

Animals↗