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Biomedical subjects

Pablo Gomez

Publications and source records attributed to Pablo Gomez.

At least 19 recordsLinked to original sources

Metastatic adenoid cystic carcinoma to the kidney in a young woman.

The incidence of an adenoid cystic carcinoma on major salivary glands is low, constituting only about 10% to 15% of all parotid malignancies. Cases of delayed metastasis have been reported, but reports of specific renal involvement have not been extensively found. We present the case of a 21-year-old woman with a left renal metastasis from an adenoid cystic carcinoma of the parotid gland that had been surgically treated 7 years previously. The patient underwent successful left radical nephrectomy. During follow-up, the patient developed pulmonary nodules that were metastatic adenoid cystic carcinoma and were surgically excised. At last follow-up, the patient was doing well with no evidence of disease.

Adult↗

HYAL1-v1, an alternatively spliced variant of HYAL1 hyaluronidase: a negative regulator of bladder cancer.

Tumor cells express HYAL1 hyaluronidase, which degrades hyaluronic acid. HYAL1 expression in bladder cancer cells promotes tumor growth, invasion, and angiogenesis. We previously described five alternatively spliced variants of HYAL1 that encode enzymatically inactive proteins. The HYAL1-v1 variant lacks a 30-amino acid sequence that is present in HYAL1. In this study, we examined whether HYAL1-v1 expression affects bladder cancer growth and invasion by stably transfecting HT1376 bladder cancer cells with a HYAL1-v1 cDNA construct. Although HYAL1-v1 transfectants expressed equivalent levels of enzymatically active HYAL1 protein when compared with vector transfectants, their conditioned medium had 4-fold less hyaluronidase activity due to a noncovalent complex formed between HYAL1 and HYAL1-v1 proteins. HYAL1-v1 transfectants grew 3- to 4-fold slower due to cell cycle arrest in the G(2)-M phase and increased apoptosis. In HYAL1-v1 transfectants, cyclin B1, cdc2/p34, and cdc25c levels were > or =2-fold lower than those in vector transfectants. The increased apoptosis in HYAL1-v1 transfectants was due to the extrinsic pathway involving Fas and Fas-associated death domain up-regulation, caspase-8 activation, and BID cleavage, leading to caspase-9 and caspase-3 activation and poly(ADP-ribose) polymerase cleavage. When implanted in athymic mice, HYAL1-v1-expressing tumors grew 3- to 4-fold slower and tumor weights at day 35 were 3- to 6-fold less than the vector tumors (P < 0.001). Whereas vector tumors were infiltrating and had high mitoses and microvessel density, HYAL1-v1 tumors were necrotic, infiltrated with neutrophils, and showed low mitoses and microvessel density. Therefore, HYAL-v1 expression may negatively regulate bladder tumor growth, infiltration, and angiogenesis.

Alternative Splicing↗

Cyclooxygenase-2 (COX-2) expression is an independent predictor of prostate cancer recurrence.

Lack of reliable prognostic markers hinders accurate prediction of disease progression in prostate cancer. The inducible proinflammatory enzyme cyclooxygenase-2 (COX-2) is implicated in prostate carcinogenesis, but its role in cancer progression is less clear. We examined whether COX-2 expression evaluated by immunohistochemistry (IHC) in radical prostatectomy (RP) specimens can predict biochemical recurrence. Archival prostate cancer specimens (n = 60) were obtained from patients who underwent RP, but had not received neoadjuvant hormonal therapy. Twenty-three patients had biochemical or clinical recurrence (mean time of recurrence: 38.2 months), and 37 patients were recurrence free (mean follow-up: 95 months). COX-2 expression was determined by IHC, using an anti-COX-2 antibody. Three individuals scored the staining independently, as high- or low-expression. COX-2 was expressed in prostate cancer cells, in adjacent normal glands and in specimens from patients who later progressed. At 62-months follow-up, COX-2 staining predicted progression with 82.4% sensitivity and 81.3% specificity. Sensitivity (86.4%) and specificity (86.7%) improved at > or = 100-months follow-up. In univariate analysis, Gleason score, preoperative PSA, extraprostatic extension, margin, seminal vesicle invasion, and high COX-2 expression were significant predictors of biochemical recurrence (p < 0.05). In multivariate analysis, preoperative PSA (hazard ratio/unit PSA change 1.080; p = 0.0036) and COX-2 expression (hazard ratio 16.442; p < 0.0001) were independent prognostic indicators. Patients with PSA > 7 ng/ml and high COX-2 expression had the highest probability of recurrence (Kaplan-Meier analysis). COX-2 expression is an independent predictor of prostate cancer progression following RP and underscores the significance of inflammatory factors in this process.

Aged↗

Prevalence of renal insufficiency in individuals with hypertension and obesity/overweight: the FATH study.

Overweight and obesity are associated with increased cardiovascular risk. Some studies have demonstrated that they also can result in renal damage. The aim of this study was to assess the prevalence of renal insufficiency (RI), defined as a GFR <60 ml/min per 1.73 m2, in a cohort of 4585 patients who attended primary care with essential hypertension and a body mass index > or =25 kg/m2. The patients were classified as overweight and obese according to body mass index (25 to 29.9 and > or =30 kg/m2, respectively). Abdominal obesity was defined as a waist circumference > or =88 and 102 cm in women and men, respectively. Both groups had a high prevalence of metabolic syndrome (Adult Treatment Panel III). The prevalence of RI was high in both the overweight group (22.7%; 95% confidence interval [CI] 20.6 to 24.9) and in the obese group (22.8%; 95% CI 21.0 to 24.7). The presence of diabetes increased the risk for RI (odds ratio 1.83; 95% CI 1.55 to 2.16). The prevalence of RI was greater in patients with abdominal obesity (23 versus 17%; P < 0.001). In the presence of abdominal obesity, cardiovascular risk factors and components of the metabolic syndrome also were more prevalent. The higher risk for RI with abdominal obesity persisted even after adjustment for dyslipidemia, elevated blood glucose levels, and other variables that are associated with RI (adjusted odds ratio 1.40; 95% CI 0.84 to 2.33). It was concluded that patients who have hypertension and visceral obesity and attend primary care present a higher prevalence of metabolic syndrome and RI.

Aged↗

Evaluation of analgesic requirements and postoperative recovery after radical retropubic prostatectomy using long-acting spinal anesthesia.

OBJECTIVES: To analyze the postoperative pain, analgesic requirements, and convalescence of patients undergoing radical retropubic prostatectomy (RRP) under spinal anesthesia using long-acting morphine sulfate as preemptive analgesia. METHODS: A total of 103 consecutive men underwent RRP by a single surgeon. The time to tolerate oral fluids, time to unassisted ambulation, postoperative pain levels (visual analog pain score of 0 to 10), and analgesic requirements expressed in morphine equivalents were evaluated. Baseline patient characteristics and intraoperative factors (operating room time, blood loss) were also evaluated. RESULTS: The mean time to tolerate oral fluids and unassisted ambulation was 11.3 +/- 7.6 hours and 20 +/- 6 hours, respectively. The mean narcotic requirements were 7.4 +/- 6.1 morphine equivalents before discharge and 28.5 +/- 25.9 morphine equivalents in the first week after discharge. The mean visual analog pain score was 4.5 +/- 2.1 at discharge and fell significantly to 1.5 +/- 1.0 by the time of Foley catheter removal on postoperative day 7 or 8. The analgesic requirements after discharge correlated with the pain score at discharge (P = 0.016). The mean time to resumption of normal preoperative activities was 19.4 +/- 9.4 days. Two patients developed postspinal anesthesia headache. No other complications attributable to the anesthetic occurred. CONCLUSIONS: RRP may be performed through a small modified Pfannenstiel incision under spinal anesthesia containing long-acting morphine with little postoperative pain, low narcotic requirements, and a short convalescence. A prospective, randomized study is needed to compare the early postoperative outcomes of RRP performed using general versus spinal anesthesia.

Analgesia↗

Comparison of the prognostic potential of hyaluronic acid, hyaluronidase (HYAL-1), CD44v6 and microvessel density for prostate cancer.

Despite the development of nomograms designed to evaluate a prostate cancer (PCa) patient's prognosis, the information has been limited to PSA, clinical stage, Gleason score and tumor volume estimates. We compared the prognostic potential of 4 histologic markers, hyaluronic acid (HA), HYAL-1-type hyaluronidase (HAase), CD44v6 and microvessel density (MVD) using immunohistochemistry. HA is a glycosaminoglycan that promotes tumor metastasis. CD44 glycoproteins serve as cell surface receptors for HA, and the CD44v6 isoform is associated with tumor metastasis. HYAL-1-type HAase is expressed in tumor cells and, like other HAases, degrades HA into angiogenic fragments. Archival PCa specimens (n=66) were obtained from patients who underwent radical prostatectomy for clinically localized PCa and had a minimum follow-up of 72 months (range 72-131 months, mean 103 months). For HA, HYAL-1 and CD44v6 staining and MVD determination, a biotinylated HA-binding protein, an anti-HYAL-1 IgG, an anti-CD44v6 IgG and an anti-CD34 IgG were used, respectively. HA and HYAL-1 staining was classified as either low- or high-grade. CD44v6 staining and MVD were evaluated quantitatively and then grouped as either low- or high-grade. Using 72 months as the cut-off limit for evaluating biochemical recurrence, HA, HYAL-1, combined HA-HYAL-1, CD44v6 and MVD staining predicted progression with 96%, 84%, 84%, 68% and 76% sensitivity, respectively. Specificity was, 61% (HA), 80.5% (HYAL-1), 87.8% (HA-HYAL-1), 56.1% (CD44v6) and 61% (MVD). Sensitivity and specificity values for each marker did not change significantly in a subset of 45 patients for whom follow-up of longer than 112 months was available. In univariate analysis using the Cox proportional hazards model, preoperative PSA, Gleason sum, margin status, seminal vesicle, extraprostatic extension (EPE), HA, HYAL-1, HA-HYAL-1 and MVD, but not CD44v6, age and clinical stage, were significant in predicting biochemical recurrence (p < 0.05). In multivariate analysis using stepwise selection, only preoperative PSA (hazard ratio/unit PSA change=1.086, p < 0.0001), EPE (hazard ratio=6.22, p=0.0016) and HYAL-1 (hazard ratio=8.196, p=0.0009)/HA-HYAL-1 (hazard ratio=5.191, p=0.0021) were independent predictors of biochemical recurrence. HA was an independent predictor of prognosis if HYAL-1 staining inference was not included in the multivariate model. In our retrospective study with 72- to 131-month follow-up, EPE, preoperative PSA and HYAL-1 either alone or together with HA (i.e., combined HA-HYAL-1) were independent prognostic indicators for PCa.

Biomarkers, Tumor↗

Radical retropubic prostatectomy in Hispanic patients.

BACKGROUND: Hispanics are the largest minority group in the U.S. Most studies assessing race as a predictor of biochemical disease recurrence after radical retropubic prostatectomy (RRP) have focused on African-American patients. To the authors' knowledge, little has been published to date regarding radical prostatectomy in Hispanic patients. Hispanics represent 29% of the patients in the current study. The authors analyzed the presentation and outcome of Hispanic males managed with radical prostatectomy. METHODS: In the current study, 1163 RRPs were performed. Patients were categorized by ethnicity as Hispanics, white non-Hispanics, African-Americans, and other ethnicities. African-American and other minority group patients were excluded from the analysis because of the small number in the current series. A comparative analysis of Hispanics and white non-Hispanics was performed. RESULTS: RRP was performed in 1163 patients. Two hundred seven Hispanic and 518 white non-Hispanic patients met the study criteria. The mean follow-up was 46.9 months. Twenty-three percent of the Hispanic patients received neoadjuvant therapy. RRP Gleason scores of 2-6, 7, and 8-10 were found in 45% of patients, 38% of patients, and in 17% of patients, respectively. Lymph node metastases were present in 3%, seminal vesicle invasion in 13%, and extraprostatic extension in 23% of Hispanic patients. Adjuvant hormonal therapy was administered to 6% of the Hispanic patients. The biochemical disease recurrence rate was 12%. The mean time to biochemical disease recurrence was 29.7 months. A comparison between the Hispanic and the white non-Hispanic groups showed no significant differences in the analyzed variables. CONCLUSIONS: Hispanic patients managed with radical prostatectomy for prostate carcinoma were found to have similar presentation, pathologic findings, and outcome as the white non-Hispanic patients.

Aged↗

Scalds in van drivers.

This report concerns 16 cases of patients admitted to our burns unit, between May 1997 and June 2003, for burns caused by the explosion of the heating system in their vehicles. In 15 of these cases, the vehicle in question was the same; the Renault Express van (P < 0.0001 in a Poisson test). While driving their vehicle, the patients suffered burns to the lower extremities and the genitals which in most cases, required surgery. Three patients suffered accidents after the scalding, due to loss of control of their vehicles. This type of injury is associated with significant complications.

Accidents, Traffic↗

Modified Pfannenstiel approach for radical retropubic prostatectomy.

Radical retropubic prostatectomy is traditionally performed using a vertical midline incision and occasionally using a transverse Pfannenstiel incision. We describe a technique for performing radical retropubic prostatectomy using a modified Pfannenstiel approach. This involves a Y incision of the rectus sheath, instead of a pure transverse incision, and provides both excellent exposure and better cosmetic results.

Esthetics↗

Urethral recurrence after cystoprostatectomy: implications for urinary diversion and monitoring.

OBJECTIVES: To review our cystoprostatectomy (CP) database to determine the urethral recurrence rate. Urethral recurrence after CP has been reported to occur in up to 10% of patients. Recent data have suggested a much lower incidence. This has important implications when considering the type of urinary diversion and postoperative monitoring. METHODS: We retrospectively analyzed our single-surgeon, consecutive CP series and determined the urethral recurrence rate and prognostic factors for recurrence. Urethrectomy was performed at CP if the prostatic apical margin was positive for carcinoma. All patients were followed up quarterly for 2 years and then semiannually. Urethral wash cytology was obtained if the patient had an ileal conduit. Cytology and cystoscopy were performed if they had an orthotopic neobladder. RESULTS: A total of 226 men had undergone radical CP. The mean age for all patients was 69 years. Eight (3.5%) had undergone urethrectomy at CP. The mean follow-up was 42 months for the remaining 218 patients, of whom 108 had an orthotopic neobladder and 110 had supravesical diversion. Of the 218 patients, 8 (3.7%) developed urethral recurrence, 7 (6.4%) in the 110 who had undergone supravesical diversion and 1 in the 108 (0.9%) who had an orthotopic neobladder. Seven patients underwent urethrectomy for the recurrence and had no evidence of disease at last follow-up. One patient died of metastatic transitional cell carcinoma at 61 months. CONCLUSIONS: In our series, the risk of urethral recurrence after radical CP was low. The risk was substantially lower for patients who had an orthotopic neobladder. Our results show that urethrectomy at CP is rarely necessary because the proximal urethral margin is usually free of cancer. An orthotopic neobladder can therefore be safely considered in most patients. Delayed urethrectomy can be safely performed in those few patients with isolated urethral recurrence without compromising their survival.

Age Factors↗

A diffusion model account of the lexical decision task.

The diffusion model for 2-choice decisions (R. Ratcliff, 1978) was applied to data from lexical decision experiments in which word frequency, proportion of high- versus low-frequency words, and type of nonword were manipulated. The model gave a good account of all of the dependent variables--accuracy, correct and error response times, and their distributions--and provided a description of how the component processes involved in the lexical decision task were affected by experimental variables. All of the variables investigated affected the rate at which information was accumulated from the stimuli--called drift rate in the model. The different drift rates observed for the various classes of stimuli can all be explained by a 2-dimensional signal-detection representation of stimulus information. The authors discuss how this representation and the diffusion model's decision process might be integrated with current models of lexical access.

Adult↗

A diffusion model analysis of the effects of aging in the lexical-decision task.

The effects of aging on response time (RT) are examined in 2 lexical-decision experiments with young and older subjects (age 60-75). The results show that the older subjects were slower than the young subjects, but more accurate. R. Ratcliff s (1978) diffusion model provided a good account of RTs, their distributions, and response accuracy. The fits show an 80-100-ms slowing of the nondecision components of RT for older subjects relative to young subjects and more conservative decision criterion settings for older subjects than for young subjects. The rates of accumulation of evidence were not significantly different for older compared with young subjects (less than 2% and 5% higher for older subjects relative to young subjects in the 2 experiments).

Adult↗

Limitations of biopsy Gleason grade: implications for counseling patients with biopsy Gleason score 6 prostate cancer.

PURPOSE: We examined the implications of underestimating Gleason score by prostate biopsy in patients with biopsy Gleason 6 prostate cancer with respect to adverse pathological findings and biochemical recurrence after radical prostatectomy. MATERIALS AND METHODS: We retrospectively reviewed clinical and pathological data on a cohort of 531 patients with Gleason score 6 on prostate biopsy who underwent radical retropubic prostatectomy between June 1992 and January 2002. Patients were excluded if they received neoadjuvant androgen deprivation. Concordance between biopsy and radical prostatectomy Gleason score was examined. A comparison was made with respect to final radical prostatectomy specimen pathology and the risk of biochemical recurrence between cases that remained Gleason 6 and those with a final grade of 7 or greater. RESULTS: A total of 451 patients were included in the analysis. Mean followup was 55.1 months (range 12 to 123.4). Of the patients 184 (41%) had a Gleason score of 7 or greater after a review of the entire prostate, while 37 (8%) had a score of less than 6 and 230 remained with Gleason 6. Patients who were under graded were more likely to have extraprostatic extension (22% vs 4%, p <0.01), seminal vesicle invasion (9% vs 2%, p <0.01) and biochemical recurrence (10% vs 3%, p <0.01) compared to those who remained with Gleason score 6. CONCLUSIONS: Gleason grade on needle biopsy is an inexact predictor of the final grade following radical prostatectomy. Patients with biopsy Gleason score 6 who are under graded are at significantly higher risk for adverse pathological features and biochemical recurrence than patients who remain with Gleason score 6 or less on final pathology findings.

Aged↗

Radionuclide bone scintigraphy in patients with biochemical recurrence after radical prostatectomy: when is it indicated?

OBJECTIVE: To evaluate the use of radionuclide bone scintigraphy following biochemical recurrence after radical retropubic prostatectomy (RRP) for localized prostate cancer. PATIENTS AND METHODS: Of 1197 patients undergoing RRP we identified those with biochemical recurrence and who had also had a bone scan. Biochemical recurrence was defined as a prostate specific antigen (PSA) level of > or = 0.4 ng/mL. Patients with indeterminate bone scan findings and those in whom the interval between the PSA test and the bone scan was >3 months were excluded. Patient age, PSA level and other relevant pathological details were recorded. Clinical symptoms at the time of bone scan, androgen deprivation after RRP, bone scintigram details and time to recurrence were documented. RESULTS: Of the 1197 patients, 153 (12.8%) had a biochemical recurrence and 35 (23%) of these had a total of 44 bone scans taken over a mean (sd) follow-up of 70.4 (35.6) months; 34 (77%) bone scans were negative (group 1) and 10 (33%) positive (group 2). In group 1 the mean PSA at the bone scan was 5.2 ng/mL; 76% of the patients had a PSA of < 7 ng/mL. In group 2 the mean PSA at the bone scan was 30.7 ng/mL and all patients had a PSA of >7 ng/mL. The only significant difference between the groups was the PSA at the time of the bone scan (P < 0.001). CONCLUSION: Bone scintigraphy is a sensitive diagnostic tool for detecting prostate cancer metastases to bone. A bone scan in patients with a serum PSA of <7 ng/mL on biochemical recurrence after RRP is unlikely to be positive, whereas a PSA of > or = 20 ng/mL is. The presence of skeletal symptoms or a PSA level of >7 ng/mL should prompt the clinician to obtain a bone scintigram.

Aged↗

Upper tract tumour after radical cystectomy for transitional cell carcinoma of the bladder: incidence and risk factors.

OBJECTIVE: To review the incidence, pattern and outcome of upper tract transitional cell carcinoma (TCC) after radical cystectomy for carcinoma of the bladder, and identify risk factors for its development. PATIENTS AND METHODS: The records of 235 consecutive patients who had a radical cystectomy and urinary diversion for TCC at the authors' institution by one surgeon between January 1992 and August 2003 were retrospectively reviewed. RESULTS: Five (2%) of 235 patients developed an upper tract urothelial tumour. The mean follow-up for all patients was 42 months, and was 52.2 months for those with an upper tract tumour. Four of the five patients presented with haematuria and one was diagnosed on routine follow-up intravenous urography. The mean time to the diagnosis of an upper tract tumour was 39.6 months. Of the potential risk factors, only the presence of TCC of the prostatic urethra had a statistically significant association with eventual upper tract tumour (P < 0.01). At the last follow-up, four patients died from urothelial cancer and one was disease-free. CONCLUSIONS: The incidence of upper tract tumour after cystectomy for TCC is low; most patients present with symptoms (haematuria) and have advanced disease at diagnosis. Patients with prostatic urethral involvement at cystectomy are at greater risk of developing upper tract tumour.

Aged↗

Effect of chemotherapy on segmental bone healing enhanced by rhBMP-2.

Segmental bone defects are challenging clinical problems, and current surgical solutions are associated with high complication rates. In oncologic reconstructive surgery, bone healing will occur coincidently with the administration of chemotherapy to treat the underlying disease. Effective methods of graft modification or bone graft alternatives can be of great help clinically. A series of osteoinductive proteins (bone morphogenetic proteins or BMPs) has been described and shown to enhance bone formation in animal models. This study was designed to evaluate the effect of chemotherapy on bone healing enhanced by rhBMP-2. We used a critical-sized bone-defect rabbit model. Histological and radiological analysis showed that chemotherapy affects both the quantity and the quality of the bone enhanced by the addition of rhBMP-2. These results suggest that the effect of chemotherapy on bone formation could be related to inhibition in a specific pathway stimulated by the rhBMP-2.

Animals↗

High-grade sarcomas mimicking traumatic intramuscular hematomas: a report of three cases.

We reported on three patients with high-grade soft-tissue sarcomas mimicking traumatic intramuscular hematomas. Patients had an episode of trauma to the extremity, and after initial clinical and imaging evaluations they were considered to have muscular hematomas. The lesions increased in size over time, leading to further evaluations that demonstrated the actual diagnosis. We conducted a retrospective review of the clinical findings, magnetic resonance images, and computed tomography scans to assess characteristics that will help in the differential diagnosis. We conclude that intramuscular hematomas following trauma should be approached with a high degree of clinical suspicion. MRI analysis can be used as an important diagnostic tool, but the results must be seen in the context of the clinical history. MRI is not sensitive or specific enough to rule out malignancy. The diagnosis of a high-grade sarcoma must be considered in these patients and any doubt should be resolved with a biopsy.

Adult↗