Biomedical subjects

Jennifer Brainard

Publications and source records attributed to Jennifer Brainard.

11 recordsLinked to original sources

PubMed2006

Thyroid-stimulating hormone receptor messenger ribonucleic acid measurement in blood as a marker for circulating thyroid cancer cells and its role in the preoperative diagnosis of thyroid cancer.

CONTEXT: Thyroid cancer cells express TSH receptor (TSHR) mRNA, and its measurement in the circulation may be useful in the diagnosis/management of differentiated thyroid cancer (DTC). OBJECTIVE: Our objective was to assess the diagnostic value of circulating TSHR mRNA for preoperative detection of DTC in patients with thyroid nodules. PATIENTS: We measured TSHR mRNA levels by RT-PCR in 258 subjects: 51 healthy subjects and 207 patients (thyroid nodules, n = 180; recurrent thyroid cancer, n = 27) with fine-needle aspirations (FNA) and/or thyroid/neck surgery. Eighty-nine patients also had d-1 postoperative levels assessed. OUTCOME MEASURES: TSHR mRNA levels were compared with FNA cytology for cancer detection preoperatively and serum thyroglobulin and/or whole-body 131I scans postoperatively. RESULTS: Based on cytology/pathology, 88 patients had DTC and 119 had benign thyroid disease. The TSHR mRNA levels in cancer patients were significantly higher than in benign disease (P < 0.0001). At a cutoff value of 1.02 ng/microg total RNA, the TSHR mRNA correctly classified 78.7% of patients preoperatively (sensitivity = 72.0%; specificity = 82.5%). Of 131 patients with FNA and surgery, 51 were FNA positive (all cancer), 17 were FNA negative (15 benign, two cancer), and 63 were indeterminate. TSHR mRNA correctly diagnosed DTC in 16 of 24 (67%) and benign disease in 29 of 39 (74%) patients with indeterminate FNA (combined sensitivity = 90%; specificity = 80%). Combining TSHR mRNA and ultrasound features for follicular lesions correctly classified all follicular cancers and could have spared surgery in 31% of these patients with benign disease. TSHR mRNA has a short life in circulation, and normalized levels on postoperative d 1 correlated with disease-free status, whereas elevated levels predicted residual/metastatic disease. CONCLUSIONS: TSHR mRNA measured with FNA enhances the preoperative detection of cancer in patients with thyroid nodules, reducing unnecessary surgeries, and immediate postoperative levels can predict residual/metastatic disease.

Adenocarcinoma, Follicular↗

PubMed2004

Endometriosis of the liver containing mullerian adenosarcoma: case report.

We present a case of a liver endometrioma in a postmenopausal woman. After failed management with leuprolide acetate, the mass was resected and contained focal areas of mullerian adenosarcoma. This is a rare case of mullerian adenosarcoma that appeared to arise within an endometrioma of the liver.

Adenosarcoma↗

PubMed2003

Molecular pathway for cancer metastasis to bone.

The molecular mechanism leading to the cancer metastasis to bone is poorly understood but yet determines prognosis and therapy. Here, we define a new molecular pathway that may account for the extraordinarily high osteotropism of prostate cancer. By using SPARC (secreted protein, acidic and rich in cysteine)-deficient mice and recombinant SPARC, we demonstrated that SPARC selectively supports the migration of highly metastatic relative to less metastatic prostate cancer cell lines to bone. Increased migration to SPARC can be traced to the activation of integrins alphaVbeta3 and alphaVbeta5 on tumor cells. Such activation is induced by an autocrine vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR)-2 loop on the tumor cells, which also supports the growth and proliferation of prostate cancer cells. A consequence of SPARC recognition by alphaVbeta5 is enhanced VEGF production. Thus, prostate cancer cells expressing VEGF/VEGFR-2 will activate alphaVbeta3 and alphaVbeta5 on their surface and use these integrins to migrate toward SPARC in bone. Within the bone environment, SPARC engagement of these integrins will stimulate growth of the tumor and further production of VEGF to support neoangiogenesis, thereby favoring the development of the metastatic tumor. Supporting this model, activated integrins were found to colocalize with VEGFR-2 in tissue samples of metastatic prostate tumors from patients.

Agar↗

PubMed2003

Metastatic knee.

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Adenocarcinoma↗

PubMed2003

Initial evaluation of Cyberknife technology for extracorporeal renal tissue ablation.

OBJECTIVES: To determine whether Cyberknife technology can be applied to renal tissue safely and effectively. The goal was to achieve the high efficacy of a surgical treatment, with the low morbidity of a noninvasive intervention. METHODS: The Cyberknife is a frameless, image-guided radiosurgical device. This innovative extracorporeal treatment combines a linear accelerator mounted on a highly maneuverable robotic arm. The Cyberknife is unique in that it divides the high-dose radiation necessary to ablate the lesion completely into up to 1200 beams. Each one of these beams of radiation has a significantly reduced dose. Therefore, the individual dose of each beam is essentially benign to the pathway and surrounding tissue. However, at the focal point of these beams, the dose is additive, and the desired ablative dose is attained. Predetermined "lesions" in 16 kidneys were treated in vivo in the porcine model. Complete treatment was accomplished in one session per animal, with no complications. Gross and histologic evaluations were completed at 4, 6, or 8 weeks. RESULTS: The degree of radiation changes correlated with longer treatment intervals. After 8 weeks, the lesions showed complete fibrosis. The zones of complete fibrosis were characterized by dense, paucicellular connective tissue completely devoid of all normal kidney elements, including tubules and glomeruli. CONCLUSIONS: This initial preclinical evaluation of the Cyberknife for extracorporeal renal tissue ablation appears to be very promising and demonstrated its ability to ablate a targeted area precisely and completely with relative sparing of the surrounding tissue. This innovative technology introduces an exciting approach as a potential treatment option of renal masses in the future.

Animals↗

PubMed2003

Ureteral tissue balloon expansion for laparoscopic bladder augmentation: survival study.

BACKGROUND AND PURPOSE: The search for the perfect urinary bladder substitute continues. Despite their inherent limitations, intestinal segments remain the commonest material for bladder reconstruction. The ureter, with its transitional epithelium, may be the ideal tissue to augment the bladder. Ikeguchi et al reported the feasibility of chronic ureteral balloon expansion by open surgery (J Urol 1998;159:1665). Herein, we propose a completely minimally invasive approach to balloon overdilate a segment of juxtavesical ureter incrementally and to use this in-line tissue-expanded ureteral patch to augment the bladder laparoscopically. MATERIALS AND METHODS: In five female pigs, a novel ureteral expansion balloon device (Microvasive, MA) was inserted percutaneously and advanced antegrade into the juxtavesical ureter. The device has two channels: one for balloon inflation and the other for draining the kidney. After progressive ureteral expansion over a 3- to 4-week period, laparoscopic augmentation ureterocystoplasty was performed. Animals were euthanized at 15 days (N = 1), 1 month (N = 1), 2 months (N = 1), and 3 months (N = 2). RESULTS: Percutaneous balloon device placement was technically successful in all five cases (mean operating room time 52 minutes). The mean volume of the tissue-expanded ureter at 1, 2, and 3 weeks was 12.9 cc, 60.3 cc, and 171.8 cc, respectively. Laparoscopic augmentation ureterocystoplasty with (N = 3) or without (N = 2) concomitant subtotal cystectomy was technically successful in all five cases without any open conversion. The mean operative time was 126.5 minutes, and the mean blood loss was 29 mL. Postoperative complications consisted of one case each of pyelonephritis and ureteral stricture. At autopsy, the mean capacity of the bladder was 574 mL, and the P(ves) at maximum capacity was 14 cm H(2)O. Histologic examination of the tissue-expanded ureter revealed regenerated transitional epithelium and muscle hypertrophy. CONCLUSIONS: Chronic ureteral tissue expansion can be carried out safely and efficaciously. The expanded tissue is thick, healthy, and vascular, with histologic features of normal transitional epithelium and muscle hypertrophy and hyperplasia. This expanded ureteral tissue can be used to augment the bladder with laparoscopic techniques. Such augmented bladders do not show significant shrinkage and possess urodynamic characteristic of normal capacity and normal compliance over a follow-up of 3 months.

Anastomosis, Surgical↗

PubMed2003

Spinal metastasis as the initial manifestation of a nonsecretory glucagonoma.

Glucagonomas are rare functional endocrine tumors of the pancreas that classically present with symptoms of glucagon excess, including rash, hyperglycemia, diarrhea, and weight loss. Metastatic disease at presentation is common but is often limited to the liver and regional lymph nodes. We describe an unusual case of a patient with glucagonoma who presented with a pathologic vertebral fracture. This tumor had no evidence of active hormone secretion but tested positive for glucagon by immunohistochemical staining.

Adult↗

PubMed2003

New advances transform the management of women with abnormal pap tests.

New advances in Papanicolaou test technology, human papillomavirus DNA testing, and revisions in the Bethesda terminology for cervical cytology have transformed the management of abnormal Pap tests. This approach has been validated by a recent randomized clinical trial, and in some instances can reduce the number of colposcopies by 50%.

Adult↗

PubMed2002

Preoperative combined nested reverse transcriptase polymerase chain reaction for prostate-specific antigen and prostate-specific membrane antigen does not correlate with pathologic stage or biochemical failure in patients with localized prostate cancer undergoing radical prostatectomy.

PURPOSE: We report a prospective study examining the ability of preoperative nested reverse transcriptase polymerase chain reaction (RT-PCR) for prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSM) to predict pathologic stage and biochemical recurrence in patients with clinically localized prostate cancer treated with radical prostatectomy. PATIENTS AND METHODS: One hundred forty-one patients were entered onto the study. Preoperative evaluation included clinical T stage, serum PSA, biopsy Gleason score, and serum RT-PCR for PSA/PSM. Univariate and multivariate logistic regression models, Kaplan-Meier estimates, and Cox proportional hazards modeling were used to identify predictors of pathologic stage and biochemical failure. RESULTS: Seventy-three patients (51.8%) were RT-PCR positive for PSA, PSM, or both. In the multivariate logistic regression model, only initial PSA was an independent predictor of pathologic stage as defined by organ-confined disease (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.00 to 1.13; P =.026) or organ-/specimen-confined disease (OR, 1.09; 95% CI, 1.02 to 1.16; P =.009). Overall Kaplan-Meier biochemical relapse-free survival (bRFS) was 85% at 59 months. Multivariate analysis of predictors for bRFS with the Cox proportional hazards model indicated that only initial PSA (OR, 1.05; 95% CI, 1.02 to 1.09; P =.004) and biopsy Gleason score (OR, 3.57; 95% CI, 1.37 to 9.58; P =.009) were independent predictors of biochemical failure. RT-PCR status did not predict pathologic stage or biochemical failure. Repeat analysis excluding 27 patients who received preoperative androgen-deprivation therapy did not change the results. CONCLUSION: Combined nested RT-PCR for PSA and PSM is not an independent predictor of pathologic stage or biochemical failure in patients with localized prostate cancer undergoing radical prostatectomy. This assay has no clinical utility in this patient population.

Antigens, Surface↗

PubMedDate not supplied

Continuing trends in pathological stage migration in radical prostatectomy specimens.

Prostate-specific antigen (PSA) screening has resulted in a profound clinical stage migration. Extracapsular extension (ECE) presents a poor prognosis after radical prostatectomy (RP). In this study the trends in rate of ECE for cancers detected by PSA screening between 1987, when PSA screening became routine in the United States, and 2001, were examined. The clinical outcome of patients (total 1505; 888 clinical Tlc, 614 clinical T2, and 3 clinical T3) with prostate cancer diagnosed by PSA screening and treated with RP without neoadjuvant hormonal therapy was analyzed. The primary outcome variable was ECE rate with respect to year of treatment for a given tumor stage, preoperative PSA level, biopsy Gleason score, and surgical Gleason score. Logistic regression analysis was used to identify predictors of ECE. Biochemical relapse-free survival (bRFS) by year of treatment was analyzed by Kaplan-Meier Curve. Rate of ECE decreased from 65.8 to 25.2% during the 15-year study duration. Multivariate analysis of clinical tumor stage, age, preoperative serum PSA level, and Gleason score confirmed that year of treatment was an independent predictor of ECE. Six-year bRFS rates (by years of treatment) were 75.1% for 1987 to 1994 and 82.6% for 1995 to 2001 (P-value = 0.0022). PSA screening has resulted in a downward pathological stage migration. These observations demonstrate improved biochemical failure rates in more recently treated patients.

Aged↗

PubMedDate not supplied

Metastatic properties of prostate cancer cells are controlled by VEGF.

Mechanisms of metastasis, the major complication of prostate cancer, are poorly understood. In this study, we define molecular mechanisms that may contribute to the highly invasive potential of prostate cancer cells. Vascular endothelial growth factor (VEGF), its receptors (VEGFRs), and alpha5beta1 integrin were expressed by prostate cancer cells in vitro and by prostate tumors in vivo, and their expression was elevated at sites of bone metastasis compared to original prostate tumor. VEGF, through interaction with its receptors, regulated adhesive and migratory properties of the cancer cells. Specifically, the highly metastatic prostate cancer cell subline LNCaP-C4-2 showed a decreased adhesive but an enhanced migratory response to fibronectin, a ligand for alpha5beta1 integrin, compared to its nonmetastatic counterpart. A similar pattern was also observed when bone sialoprotein was used as a ligand in migration assays. Increased migration of metastatic prostate cancer cells to fibronectin and bone sialoprotein was regulated by VEGF via VEGFR-2. Tumor suppressor PTEN was involved in control of VEGF/VEGFR-2 stimulated prostate cancer cell adhesion as well as proliferation.

Bone Neoplasms↗