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David G Bostwick

Publications and source records attributed to David G Bostwick.

52 records · Page 3Linked to original sources
PubMed2003

Adenoid cystic/basal cell carcinoma of the prostate: clinicopathologic findings in 19 cases.

Adenoid cystic/basal cell carcinoma (ACBCC) of the prostate has been considered to have indolent biologic potential. However, outcome data are scant, with only one documented metastasis and death. We describe clinicopathologic features of ACBCC in 19 patients and document outcome in 15. Patients ranged in age from 43 to 83 years. All but one presented with urinary obstruction. ACBCC was diagnosed by transurethral resection in 15 cases, by needle biopsy in 3 cases, and unexpected in 1 case. Four patients had concurrent acinar adenocarcinoma. Histologically, cribriform or adenoid cystic patterns predominated in 12 cases and basal cell carcinoma pattern in 7. Five cases had prominent perineural invasion. ACBCC was immunoreactive for p63 and cytokeratins 7 and 34 beta E12 but not cytokeratin 20. After diagnosis, 5 patients underwent radical prostatectomy, 2 underwent pelvic exenteration, and the rest had no treatment. ACBCC showed extraprostatic extension in 5 cases and involved the bladder margin in 3. Metastases developed in 4 (21%) patients: liver (2), lung (2), bowel (1), and corpus cavernosum (1). In 15 cases with follow-up (0.3-11.8 years), two patients died of cancer (at 1.5 and 3 years after diagnosis), 3 remain alive with cancer, and 10 have no evidence of cancer. Thus, ACBCC of the prostate is a potentially aggressive neoplasm requiring ablative therapy.

Adult↗
PubMed2003

Molecular differentiation of high- and moderate-grade human prostate cancer by cDNA microarray analysis.

The prognosis of men with moderate-grade prostate cancer is uncertain. At present, there are few if any reliable molecular markers that can distinguish moderate-grade tumors from those that behave more aggressively. To better understand the molecular basis of human prostate cancer and potentially provide information toward more accurate prognosis, we measured and analyzed gene expression profiles of 13 high- and moderate-grade human prostate tumors using cDNA microarrays. The expression of 136 genes was observed to differ significantly (P < 0.001) between normal prostate and tumors using one-sample t testing and Wilcoxon ranking. Hierarchical clustering of genes demonstrated a relatively similar pattern of differential expression across the tumors. However, importantly, permutation t tests (two-tailed P < 0.001) revealed 21 genes whose expression profiles segregated moderate- and high-grade tumors from each other, which was significantly (P < 0.03) greater than what was expected by chance. These results were compared in silico with prostate cancer profiling efforts performed by other groups, including a meta-analysis of four data sets, which validated many of the dysregulated genes. We suggest that these data provide insight into the molecular nature of clinically aggressive prostate cancer.

Adenocarcinoma↗
PubMed2003

Histological changes of minimally invasive procedures for the treatment of benign prostatic hyperplasia and prostate cancer: clinical implications.

PURPOSE: Benign prostatic hyperplasia (BPH) is near universal in aging men, creating tremendous costs in morbidity and surgical treatment. In the last decade numerous nonsurgical minimally invasive methods have emerged for ablation of prostatic tissue. MATERIALS AND METHODS: We reviewed the recently published English language literature on minimally invasive techniques for treating BPH and cancer with an emphasis on histopathological findings. RESULTS: We compared the spectrum of contemporary minimally invasive treatments for BPH and cancer, with an emphasis on histopathological results. Clinical results were summarized briefly for each treatment method. These procedures ablate tissue by thermal, cryogenic, chemical or enzymatic injury. The 5-year results for some techniques were promising, although long-term durability is still uncertain, and other methods were in preclinical or early clinical stages. Invariably the treated tissue was devitalized with a thin border of granulation tissue and fibrosis. These procedures have applications for BPH and prostate cancer, although some studies are limited to only 1 disease. CONCLUSIONS: Minimally invasive procedures show promise of a durable replacement for surgical resection.

Animals↗
PubMed2003

Fast liquid ablation system for prostatic hyperplasia: a new minimally invasive thermal treatment.

PURPOSE: We determined patient tolerance and the sequence of histopathological changes of thermal injury and healing of the prostate after treatment with a novel, rapid, high temperature, liquid filled, flexible balloon thermotherapy system. MATERIALS AND METHODS: A total of 17 patients scheduled for prostatic surgery received preoperative high temperature water balloon thermotherapy. In 13 patients intraprostatic, urethral and rectal temperatures were continuously monitored and determined using stereotactic thermal mapping with the patient under spinal anesthesia. The remaining 4 patients had lidocaine gel as the only method of pain control. Patient discomfort was recorded at all times during the procedure. After treatment a prostatic stent was left in place until surgery or spontaneous voiding. Serial sections of the resected prostates were evaluated pathologically with mapping. RESULTS: Treatment was well tolerated by all patients. Prostates were enucleated (in 12 patients) or entirely removed (in 5) at a mean of 35 days (range 15 to 173) after thermotherapy. The predominant pathological findings in the early phase were uniform periurethral hemorrhagic necrosis, extensive urothelial denudation and varying degrees of inflammation. The mean radial depth of necrosis (from the urethra to the viable tissue border) was 0.9 cm (range 0.6 to 1.5) involving a mean of 16% of the prostatic adenoma (range 7.8% to 32%). In the late (resolution) phase necrotic tissue had been replaced by scar tissue (fibrosis and hyalinization) with a mean radial depth of 0.13 cm (range 0.01 to 0.24), and the urothelium had largely regrown along the urethra. CONCLUSIONS: The fast liquid ablation system for hyperplasia is a new minimally invasive treatment that induces considerable thermal injury to the prostate with uniform necrosis and subsequent sloughing of dead tissue, allowing enlargement of the urethral lumen.

Aged↗
PubMed2003

Mesonephric remnants of the prostate: incidence and histologic spectrum.

Mesonephric remnants in the prostate are an unusual mimic of adenocarcinoma with unknown incidence. This condition is considered benign, similar to its counterpart in the female genital tract, but there have only been six cases reported to date, so the histologic spectrum of this finding is uncertain. To determine the incidence and comparative histopathology of this finding, we reviewed all transurethral resections of the prostate obtained at Mayo Clinic (Rochester, MN) in 1989 to identify cases of mesonephric remnants. Among 698 prostatic transurethral resection specimens, we identified 4 cases of mesonephric remnants (0.6% incidence), all in association with nodular hyperplasia. Patients ranged in age from 66 to 82 years (mean, 72 y) and had typical urinary obstructive symptoms; follow-up was obtained in these 4 cases. Four additional consultation cases and one needle biopsy case were also included in this study. Histologically, mesonephric remnants consisted of a proliferation of benign acini arranged in lobules or showing infiltrative growth between smooth muscle bundles without stromal desmoplasia. The acini were typically round or oval, varied in size and spacing, and lined by a single layer of low cuboidal cells with scant to moderate cytoplasm and inconspicuous small nucleoli. The cells of mesonephric remnants were not reactive with antibodies to prostate-specific antigen (eight of eight cases) or with prostatic acid phosphatase (seven of seven cases); high-molecular weight cytokeratin 34betaE12 was positive in the basal cells (six of eight cases). Our results indicate that mesonephric remnants are present in <1% of transurethral resections and are rarely identified in needle biopsies. The acini are lobular or infiltrative and may be architecturally mistaken for adenocarcinoma. This cytologically innocuous finding is probably underreported and interpreted as benign prostatic acini, but this is of no apparent clinical consequence. Immunohistochemical studies with antibodies to PSA and keratin 34BE12 are helpful in separating mesonephric remnants from adenocarcinoma, similar to the case of other benign mimics.

Adenocarcinoma↗
PubMed2003

Distinguishing atrophy and high-grade prostatic intraepithelial neoplasia from prostatic adenocarcinoma with and without previous adjuvant hormone therapy with the aid of cytokeratin 5/6.

We evaluated the sensitivity and specificity of cytokeratin (CK) 5/6 for distinguishing foci of atrophy from prostatic adenocarcinoma with and without previous hormonal adjuvant therapy and observed the intensity and pattern of staining in mimickers of prostatic adenocarcinoma (basal cell hyperplasia, atypical adenomatous hyperplasia, and tangentially cut high-grade prostatic intraepithelial neoplasia [PIN]). We reviewed 146 acinar proliferations in 81 specimens (radical prostatectomy, previously untreated, 41; radical prostatectomy, following androgen-deprivation therapy, 11; transurethral resection, previously untreated, 29). All benign acinar proliferations stained positively for CK5/6, with immunoreactivity restricted to basal cells. Untreated and androgen-deprived prostatic adenocarcinomas were invariably negative. The pattern of staining was continuous in 79% of the atrophy cases (15/19), and all foci stained with CK5/6. Characteristic double-layer staining in basal cell hyperplasia was observed in 93% of cases (13/14), and foci of high-grade PIN had a characteristic "checkerboard" staining with areas of discontinuity. Foci of atypical adenomatous hyperplasia showed continuous staining, including cauterized acini in 53% of cases (8/15), with a fragmented basal cell layer pattern in 47% of cases (7/15). CK5/6 staining of the basal cells in foci of atrophy is sensitive and specific for excluding prostatic adenocarcinoma with and without androgen-deprivation effect.

Adenocarcinoma↗
PubMed2002

Urothelial papillary (exophytic) neoplasms.

The contemporary classification and grading of human papillary urothelial neoplasms remains unsettled, with multiple recent suggestions by groups of pathologists with little or no clinical input. One of the chief motivations for these new approaches was to avoid use of the term "cancer" for neoplasms with a low likelihood of invasion, recurrence, and death. Also, critics contended that earlier grading schemes were too imprecise to be clinically useful. We summarize the work carried out by the majority of members of Committee No. 1 at the International Consultation on the Diagnosis of Non-Invasive Urothelial Neoplasms held in Ancona, Italy (11-12 May 2001). Our deliberations represent a multidisciplinary international effort based on the best available data and the perception of existing practical methods of classification by clinicians, pathologists, and cancer registrars. The WHO 1973 classification for papillary urothelial neoplasms (papilloma, grade 1, grade 2, and grade 3 carcinoma) is still superior to all existing alternatives (such as WHO/ISUP 1998 and WHO 1999), although some refinement of diagnostic criteria would be useful. Some pathologists may prefer additionally to report synonymous classification in other schemes, but this is discouraged owing to variations and difficulties in translations.

Carcinoma, Papillary↗
PubMed2002

Determination of a minimal deletion interval on chromosome band 8p21 in sporadic prostate cancer.

Loss of the short arm of chromosome 8 is a common event in prostatic neoplasms. Previous studies indicate that there may be up to three separate tumor suppressor genes on chromosome arm 8p, based on patterns of allelic loss. The responsible gene or genes have yet to be identified. In the present study, we used laser-capture microdissection of primary human prostate tumors and 17 microsatellite markers across chromosome band 8p21 to determine a minimal deletion interval. From an initial set of 120 cases, three tumors contained overlapping interstitial deletions on chromosome band 8p21. The three cases define an internally consistent minimal candidate tumor suppressor gene interval of approximately two megabases.

Chromosome Banding↗
PubMed2002

Neuroendocrine expression in node positive prostate cancer: correlation with systemic progression and patient survival.

PURPOSE: Neuroendocrine cells are ubiquitous but uncommon in benign and neoplastic prostate epithelium, and they are considered important for regulating cell growth and differentiation. The predictive value of neuroendocrine immunoreactivity for patient outcome after radical prostatectomy is uncertain. In this study we determined the expression of 2 important neuroendocrine markers, chromogranin and serotonin, in benign epithelium, primary prostate cancer and lymph node metastases, and correlated cellular expression with patient outcome. MATERIALS AND METHODS: We studied 196 patients with node positive prostate adenocarcinoma who underwent bilateral pelvic lymphadenectomy and radical prostatectomy at Mayo Clinic between 1987 and 1992. Mean followup was 6.8 years (range 0.3 to 11). The cellular expression of chromogranin and serotonin in matched samples of benign tissue, primary prostate cancer and lymph node metastases from the same patients was evaluated by immunohistochemical staining using commercially available monoclonal antibodies. Results were correlated with patient age, pathological findings (Gleason score, DNA ploidy and cancer volume) and patient outcome, including clinical progression, cancer specific and all cause survival. RESULTS: Chromogranin immunoreactivity was greater in benign prostatic epithelium and primary cancer cases (99% each) than in those of lymph node metastases (37.5%) (pairwise comparisons with metastases p <0.001). The mean incidence of immunoreactive cells in benign epithelium, primary cancer and metastases was 6% (median 5%), 6% (median 3%) and 2.2% (median 0%), respectively. Serotonin immunoreactivity was greatest in benign prostate epithelium cases (98.5%) with less in primary cancer (95%) and lymph node metastases (21.5%) (pairwise comparisons p <0.001). The mean incidence of immunoreactive cells in benign epithelium, primary cancer and metastases was 2.2% (median 3%), 2.4% (median 2%) and 0.4% (median 0%), respectively. Chromogranin expression was invariably greater than that of serotonin for all 3 diagnostic categories (p <0.0001). There was a marginally significant positive trend in the level of chromogranin expression in benign prostatic epithelium and systemic progression (p = 0.05) but no significant association with cancer specific or all cause survival (p >0.1). No significant association was observed of chromogranin expression in primary cancer or lymph node metastases with any patient outcomes (p >0.1). There was a significant association of the level of serotonin expression in benign prostatic epithelium with cancer specific survival (p = 0.03) but no significant association with systemic progression or all cause survival (p > 0.1). There were positive trends in the association of serotonin immunoreactivity in primary cancer with systemic progression (p = 0.09) and cancer specific survival (p = 0.05) but not with all cause survival (p >0.1). No significant association was observed of serotonin expression in lymph node metastases with any patient outcomes (p >0.1). CONCLUSIONS: Benign prostatic epithelium and primary prostate cancer express a significantly greater number of chromogranin and serotonin immunoreactive cells than lymph node metastases, suggesting that decreased expression of neuroendocrine markers is involved in cancer progression. However, neuroendocrine expression was marginally useful for predicting the outcome in patients with node positive prostate cancer treated with radical prostatectomy.

Adenocarcinoma↗
PubMed2002

Needle core length in sextant biopsy influences prostate cancer detection rate.

OBJECTIVES: Prostate cancer detection in biopsies increases with the number of sites and total tissue sampled. Its dependence on needle core fragment length is uncertain. METHODS: We surveyed two consecutive series of sextant needle biopsies from two practices in 1998 to 2000: 251 patients from Pennsylvania (group P) and 1596 from Virginia (group V). We tabulated the gross needle core lengths per sextant site and classified the diagnoses as benign or into four nonbenign categories: high-grade prostatic intraepithelial neoplasia; atypical small acinar proliferation, suspicious; atypical small acinar proliferation, suspicious plus high-grade prostatic intraepithelial neoplasia; and cancer. Logistic regression analysis was used to correlate cancer or a nonbenign diagnosis with the total length (sum of six sites) and, after excluding the sites with more than one core, with the length per single core, and the anatomic site of origin (apex, mid-gland, base). RESULTS: The mean total tissue length sampled was 108 +/- 27 mm (range 30 to 275) in group P and 81 +/- 22 mm (range 30 to 228) in group V. Sextant sites with a single core contained a mean of 12.8 +/- 3.5 mm tissue, with a 3.6-fold variation among the middle 95%. Group V core lengths at the apex averaged 11.8 mm, shorter (P = 0.0001) than mid (13.3 mm) or base (12.7 mm). A predictive value of longer length for a nonbenign diagnosis was noted in four of six sextants (P <0.04), with trend strongest at the apex, for which detection was influenced by abnormal digital rectal examination (P = 0.02) or ultrasound (P = 0.04) findings. CONCLUSIONS: The length of single cores sampled by sextant biopsy can vary more than 3.6-fold and represents a quality assurance consideration. The effect of length on cancer or nonbenign detection was maximal at the prostatic apex where the cores were shortest.

Biopsy, Needle↗
PubMed2002

Loss of p53 and c-myc overrepresentation in stage T(2-3)N(1-3)M(0) prostate cancer are potential markers for cancer progression.

To determine whether genetic changes are markers of cancer progression and patient survival in Stage T(2-3)N(1-3)M(0) prostatic carcinoma, we compared 26 patients who died of tumor relapse after prostatectomy and lymphadenectomy (case group) with 26 matched patients who were alive at the time of the matched case's death (control group). Nine unmatched cases were also included in this study. In 37 cases, paired primary tumors (119 foci) and lymph node metastases (114 foci) were available for study. Fluorescence in situ hybridization (FISH) with centromere-specific probes for chromosomes 7, 8, and 17 and region-specific probes for D7S486 (7q31), c-myc (8q24), LPL (8p22), and p53 (17p13) was performed on available primary carcinomas and lymph node metastases. In primary tumor foci, +7q31, -8p22, +c-myc, substantial additional increases of myc (AI-c-myc), and -p53 were observed in 65%, 74%, 43%, 29%, and 31% of foci, respectively. AI-c-myc was strongly associated with higher cancer Gleason score (P =.003). Heterogeneity of genetic changes was frequently observed among multiple cancer foci. Lymph node metastases of prostate cancer usually shared genetic changes with paired primary tumors. In addition, the genetic change pattern with -8p, +c-myc or AI-c-myc, +7q, and +p53 was slightly higher in lymph node metastases (22%) than in primary tumors (6%) (P =.08). In matched case and control patients, simultaneous gain of 7q31 (+7q31) and CEP7 (+CEP7) was identified in 59% and 68% of specimens for case and control groups, respectively (P =.48). Loss of 8p22 (-8p22) was identified in 77% and 69% of specimens for case and control groups, respectively (P = 1.0). Simultaneous gain of c-myc (+c-myc) and CEP8 (+CEP8) without overt additional increase of c-myc copy number relative to CEP8 copy number, was identified in 38% and 54% of specimens for case and control groups, respectively (P =.27). AI-c-myc was identified in 54% and 23% of specimens for case and control groups, respectively (odds ratio = 3.0, P =.06). Loss of p53 (-p53) was identified in 46% and 15% of specimens for case and control groups, respectively (odds ratio = 4.0, P =.04). Our results indicate that FISH anomalies are very common in both primary tumors and lymph node metastases of Stage T(2-3)N(1-3)M(0) prostate cancer; that AI-c-myc is associated with higher cancer Gleason score; that AI-c-myc and -p53 are associated with prostate cancer progression and are potential markers of survival in Stage T(2-3)N(1-3)M(0) prostate cancer; and that lymph node metastases usually have similar or additional genetic changes compared with primary tumors, and multiple lymph node metastases usually have similar genetic changes.

Aged↗
PubMed2002

Ferromagnetic self-regulating reheatable thermal rod implants for in situ tissue ablation.

BACKGROUND AND PURPOSE: Ferromagnetic compounds, when placed in a radiofrequency magnetic field, develop an electrical current. When placed in tissue, resistance to the transmission of the electrical current leads to heating of the tissues next to the ferromagnetic compound. The Curie temperature is a transition point at which the development of a particular temperature within the material results in loss of its magnetic properties; as such, when this temperature is reached, there is cessation of current, and thus heat production stops. Our goal was to examine the ablative impact of permanently implanted palladium and cobalt self-regulating temperature rods on solid abdominal and pelvic organs. These rods were designed to develop a maximum temperature of 70 degrees C. MATERIALS AND METHODS: In 16 pigs, renal, hepatic, uterine, and pancreatic ferromagnetic rods were placed using a template. The rods were delivered in 1-cm parallel rows of two rods each in order to ablate 7 g of tissue. The animals were subsequently treated in an extracorporeal magnetic field of 50 gauss rms at a frequency of 50 kHz. The position of the rods was confirmed by fluoroscopy before the animal was put in the magnetic field. The animals received one or two treatment sessions. Intralesional and extralesional temperatures were measured continuously. Serum chemistry was analyzed before surgery, after each treatment, and at the time of harvest. Two weeks following therapy, the treated tissues were harvested and examined histopathologically. RESULTS: In all tissues with properly aligned rods, the temperature of the tissue surrounding the rods exceeded 50 degrees C. Histologic review showed confluent tissue necrosis in 7 of 9 kidneys (78%), 6 of 9 livers (67%), 1 of 3 pancreases (33%), and 1 of 3 uterine specimens (33%). Necrosis extended for 2 mm beyond the periphery of the rods. All failures were secondary to technical misalignment of the rods, which occurred because of our attempt to treat more than one organ in each animal. CONCLUSIONS: Ferromagnetic rods, when properly aligned in a magnetic field, create well-defined areas of necrosis. There are no skip areas of viable tissue within the treated area, and there is a precipitous fall-off of injury just outside the area of treatment. Also, because the rods can be reactivated at any time, recurrent lesions within the same site can be treated. This form of minimally invasive in situ ablative therapy appears promising. Clinical trials in the kidney and in other abdominal and pelvic organs are pending.

Animals↗
PubMed2002

Laparoscopic partial nephrectomy with a novel electrosurgical snare in a porcine model.

PURPOSE: We evaluated the safety and efficacy of laparoscopic partial nephrectomy with an arcing-gap electrosurgical snare in a porcine model. MATERIALS AND METHODS: A novel electrosurgical snare, optimizing high current density arcing and parenchymal compression, was utilized for laparoscopic renal transection. Five farm pigs underwent unilateral laparoscopic polar partial nephrectomy; 6 weeks later, these same animals underwent contralateral partial nephrectomy just prior to sacrifice. Five additional animals underwent chronic (6-week follow-up) and acute open partial nephrectomies by the conventional surgical technique. RESULTS: The average time for transection with the snare was 5.6 minutes. In 9 of 10 cases, the snare provided satisfactory hemostasis. In the remaining case, additional argon-beam coagulation (ABC) controlled the minimal bleeding present after transection. In all 10 animals, the collecting system was transected. In six cases, application of the snare alone sealed the collecting system. No urinomas developed in the five animals followed for 6 weeks. At 6 weeks, the mean depth of injury at the center of the cut surface was 5.1 mm in the laparoscopic group and 3.9 mm in the open group. CONCLUSIONS: Laparoscopic partial nephrectomy with the arcing-gap electrosurgical snare is feasible in a porcine model. Application of the snare provides excellent hemostasis without the need to control the renal vasculature.

Animals↗
PubMedDate not supplied

Flutamide in men with prostatic intraepithelial neoplasia: a randomized, placebo-controlled chemoprevention trial.

High-grade prostatic intraepithelial neoplasia (HGPIN) has been identified as a premalignant change in the prostate that indicates increased risk of the subsequent development of prostate adenocarcinoma. Prior studies have suggested that androgen deprivation therapy causes a regression of HGPIN. We therefore conducted a chemoprevention trial assessing the efficacy of flutamide in reducing the rate of prostate adenocarcinoma development in men with HGPIN. Men with biopsyproven HGPIN but no evidence of prostate adenocarcinoma were randomized in a double-blind manner to either flutamide 250 mg/d or a placebo. Treatment was continued for 1 year. Repeat biopsies were obtained at 12 and 24 months. Quality of life and toxicities related to treatment were also measured. Sixty patients were randomized and began therapy with either flutamide or placebo. At 1 year, 14% of men receiving flutamide and 10% of men receiving placebo had developed prostate adenocarcinoma. Flutamide-associated toxicities were mild to moderate in severity. Quality-of-life measures did not show any differences between the 2 groups. This study showed no evidence of benefit from flutamide as a chemoprevention agent in men with HGPIN.

Aged↗