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Richard S Foster

Publications and source records attributed to Richard S Foster.

31 records · Page 2Linked to original sources

Molecular genetic alterations in the laser-capture-microdissected stroma adjacent to bladder carcinoma.

BACKGROUND: Urothelial carcinoma commonly manifested loss of heterozygosity (LOH) at different regions of chromosomes 17p, 3p, and 9q. Recent studies suggested that bladder stromal cells may be implicated in the growth and progression of urothelial carcinoma. To better understand the genetic alterations in the stromal cells in patients with bladder carcinoma, the authors evaluated the prevalence of allelic loss at three microsatellite polymorphic markers on chromosomes 17p13 (TP53), 3p25-26 (D3S3050), and 9q32-33 (D9S177). In addition, the pattern of X-chromosome inactivation of the stromal cells was evaluated by analyzing the DNA methylation pattern at a polymorphic site on the androgen receptor gene. METHODS: The authors studied 18 female patients who underwent either transurethral resection (n = 2) or radical cystectomy (n = 16) for high-grade muscle-invasive urothelial carcinoma of the urinary bladder. Genomic DNA samples from the stromal cells immediately adjacent to the tumor and the tumor itself were prepared from formalin-fixed, paraffin-processed tissues using laser-assisted microdissection and LOH was determined. RESULTS: The stromal cells showed a high frequency of LOH on chromosomes 17p13 (29%), 3p25-26 (61%), and 9q32-33 (47%) with no clear concordance with the adjacent tumor cells. Fourteen specimens (78%) showed LOH in the stroma in at least 1 of 3 markers examined. Nonrandom X-chromosome inactivation was frequent in the stromal cells (50% of informative specimens). CONCLUSIONS: The current study revealed that some of the genetic changes that commonly occur with invasive urothelial carcinoma were frequently found in the adjacent stroma and suggested that the stroma of urothelial carcinoma may play an important role in bladder carcinogenesis.

Carcinoma, Transitional Cell↗

Stroma adjacent to metastatic mature teratoma after chemotherapy for testicular germ cell tumors is derived from the same progenitor cells as the teratoma.

Metastatic mature teratoma is often present in postchemotherapy surgical specimens of lymph nodes from patients with pathological stage II or III testicular germ cell tumors. The stromal cells in these lesions have generally been considered "fibrosis" secondary to the chemotherapy and the necrosis it causes, although the frequent cytological atypia of the stromal cells suggests that they may be neoplastic. We studied 25 patients with pathological stage II or III testicular cancer who were treated with platinum-based chemotherapy followed by surgical resection of retroperitoneal lymph nodes that contained metastatic mature teratoma with "fibrosis" to determine the reactive or neoplastic nature of the stromal cells. We compared the pattern of allelic loss using nine microsatellite DNA markers (D9S177, D9S303, D9S778, D9S171, D12S1015, D1S508, D2S156, D18S46, and D11S903) between the epithelial cells of the teratoma and the cells in the adjacent stroma. A laser capture microdissection technique facilitated preparation of genomic DNA from the epithelial components of teratoma, adjacent stromal cells, and normal lymph node tissue from each patient. Of the 25 patients, loss of heterozygosity was seen at a minimum of one focus in 22 (92%) of the teratoma specimens and 16 (64%) of the adjacent stroma. Of the 16 cases for which the stroma showed loss of heterozygosity, 8 cases showed the identical pattern of allelic loss in the epithelial cells of the adjacent teratoma at all nine DNA loci studied. The remaining eight cases showed similar allelic loss in at least one of the nine DNA loci analyzed. Interestingly, three cases showed loss of heterozygosity in the stroma that was not seen in the matching teratoma specimens. Our results indicate that the stromal cells adjacent to metastatic mature teratoma in postchemotherapy lymph node specimens frequently have genetic abnormalities similar to the metastatic teratoma. Concordant genetic alterations observed in teratoma and stroma suggest that both are derived from the same element of the original germ cell tumor or the same progenitor cell.

Adult↗

Does retroperitoneal lymph node dissection have a curative role for patients with sex cord-stromal testicular tumors?

BACKGROUND: Sex cord-stromal tumors account for < 5% of all adult testicular tumors, and 10% are malignant. Due to the limited reported experience, there is no agreement on the best management, especially in patients who have tumors with malignant pathologic features or who present with metastatic disease. The authors attempt to evaluate the role of retroperitoneal lymph node dissection (RPLND) in the management of patients with these malignant sex cord-stromal tumors. METHODS: Reviewing the Indiana University testis cancer registry revealed 17 patients who underwent RPLND for sex cord-stromal tumors. Pathology was reviewed for features suggestive of malignancy. The data examined included clinical and pathologic stage, surgical procedure, additional therapy received, and outcome. RESULTS: Pathology included Leydig tumors in six patients, Sertoli tumors in four patients, sex cord-stromal tumors in five patients, a granulosa cell tumor in one patient, and a poorly differentiated non-germ cell tumor in one patient. Nine patients had histologic features suggestive of malignancy. Clinical stage at surgery was Stage I in nine patients and Stage IIA-IIIA in eight patients. Patients underwent modified or bilateral RPLND. Nine patients had pathologic Stage I tumors, and the remaining eight patients and had pathologic Stage IIB-IIIA tumors. Follow-up ranged from 8 months to 11 years. Of the eight patients with Stage II-III disease, six patients eventually died of metastatic disease despite additional radiotherapy and/or chemotherapy. CONCLUSIONS: Sex cord-stromal tumors have a potentially aggressive malignant behavior that is difficult to predict based on clinical and pathologic features. Although the therapeutic role of RPLND in patients with small-volume metastatic retroperitoneal tumors is unclear, RPLND remains an option to be performed immediately after orchiectomy, especially in patients who have tumors with malignant features and/or small-volume metastatic disease.

Adult↗

Anatomic distribution of periprostatic adipose tissue: a mapping study of 100 radical prostatectomy specimens.

BACKGROUND: Because the prostatic capsule is often indistinct, recognition of extraprostatic extension by carcinoma depends heavily on the identification of carcinoma cells in the periprostatic adipose tissue. However, the distribution of adipose tissue along the prostatic surfaces has not been studied extensively. METHODS: The authors analyzed the periprostatic adipose tissue in specimens from 100 patients treated with radical retropubic prostatectomy and bilateral pelvic lymphadenectomy for prostatecarcinoma. Each specimen was totally embedded and examined by the whole mount method. The presence or absence of adipose tissue on the anterior, posterior, right, and left surfaces of the prostate was determined and analyzed. RESULTS: Periprostatic adipose tissue was present on 48% of all prostatic surfaces examined. The distribution of periprostatic adipose tissue varied among the different surfaces of the prostate, with the anterior, posterior, right, and left surfaces showing 44%, 36%, 59%, and 57% adipose tissue, respectively. The amount of periprostatic adipose tissue was similar among specimens from operations performed by different surgeons (P = 0.72). However, nerve-sparing procedures resulted in less adipose tissue (46%) than non-nerve-sparing procedures (54%) (P = 0.01). CONCLUSIONS: Less than half of the prostatic surfaces examined were covered by adipose tissue. The absence of adipose tissue over large areas of the prostatic surface, especially the posterior surface, makes the evaluation of extraprostatic extension difficult and unreliable. Further refinement of the prostate carcinoma staging system is needed.

Adipose Tissue↗

Update on late relapse of germ cell tumor: a clinical and molecular analysis.

PURPOSE: Analysis of patients with late relapse (LR) of germ cell tumor (GCT) with reports on clinical characteristics, outcomes, and molecular and cytogenetic features. PATIENTS AND METHODS: Eighty-three patients evaluated at Indiana University from 1993 through 2000 for relapse of GCT more than 2 years from initial therapy were reviewed. Available specimens were investigated for expression of the transcription regulator FoxD3 and apurinic/apyrimidinic endonuclease and the presence of chromosome 12 abnormalities. RESULTS: Median interval from initial presentation to LR was 85 months. Forty-three of 49 LR patients who underwent surgery were rendered disease free (NED), and 20 (46.5%) remain continuously NED. Thirty-two patients received chemotherapy, but only six (18.8%) obtained a complete remission. Five of these patients remain continuously NED after chemotherapy alone, including three who were chemotherapy naïve. Eighteen of these 32 patients were successfully rendered NED by postchemotherapy surgery, and 12 remain continuously NED. Two patients continue on observation with no treatment for their LR. Overall, 69 of the 81 treated patients (85.2%) ultimately achieved an NED state, and 38 (46.9%) remain continuously NED with median follow-up from LR therapy of 24.5 months (range, 1 to 83 months), whereas nine other patients are currently NED after therapy for subsequent relapses. Because of the small numbers of specimens tested, we were unable to draw any definitive conclusions from the molecular and cytogenetic analyses. CONCLUSION: GCT patients require lifetime follow-up. At the time of LR, surgical resection alone remains our preferred therapy.

Adult↗

Identical allelic losses in mature teratoma and other histologic components of malignant mixed germ cell tumors of the testis.

Teratomas of the testis in post-pubertal patients are histologically diverse tumors that often coexist with other types of germ cell tumors. Using laser capture microdissection and loss of heterozygosity analysis, we investigated the clonality of mature teratoma and its relationship to other components of malignant mixed germ cell tumors to gain potential insight into the histogenetic relationship of teratoma with other germ cell tumor components. All 16 patients had mature teratoma as one component of their mixed germ cell tumors. The other histological subtypes included immature teratoma, seminoma, embryonal carcinoma, yolk sac tumor, and choriocarcinoma. Laser-assisted microdissection was performed on the formalin-fixed, paraffin-embedded tissue. Polymerase chain reaction was used to amplify genomic DNA at specific loci on chromosome 1p36.2 (D1S508), 2q22-32 (D2S156), 9p21-22 (D9S162), 11p13 (D11S903), 12q22-23 (D12S1051), and 18q21 (D18S46). Fourteen of 16 (88%) cases showed allelic loss in one or more components of the mixed germ cell tumors. Fourteen of 16 mature teratomas showed allelic loss in at least one of six microsatellite polymorphic markers analyzed. The frequency of allelic loss in mature teratoma was 50% (7 of 14) with D1S508, 33% (5 of 15) with D2S156, 58% (7 of 12) with D9S162, 43% (6 of 14) with D11S903, 20% (3 of 15) with D12S1051, and 33% (5 of 15) with D18S46. Completely concordant allelic loss patterns between mature teratoma and all of the other germ cell tumor components were seen in 10 of 14 tumors in which mature teratoma showed loss of heterozygosity. Our data support the common clonal origin of mature teratoma with other components of malignant mixed germ cell tumors of the testis.

Adolescent↗

Prostate carcinoma presenting as multiple pulmonary nodules in an asymptomatic patient with a history of testicular nonseminomatous germ cell tumor.

Prostate carcinoma presenting initially as multiple pulmonary nodules in an asymptomatic patient without previous prostate carcinoma is unusual. Whether the incidence of prostate carcinoma is significantly increased in patients treated previously for germ cell tumors is unclear. We report such a patient, who responded to combination androgen blockade therapy.

Adenocarcinoma↗

Is post-chemotherapy resection of seminomatous elements associated with higher acute morbidity?

PURPOSE: A seminomatous element in patients undergoing retroperitoneal lymph node dissection for testicular cancer is associated with a desmoplastic reaction that renders retroperitoneal surgery more challenging. We examined the impact of seminomatous elements on the rate of complications and the need for additional intraoperative procedures in patients undergoing post-chemotherapy retroperitoneal lymph node dissection. MATERIALS AND METHODS: The testis cancer data base at our institution was retrospectively reviewed and 1,366 patients were identified who underwent post-chemotherapy retroperitoneal lymph node dissection between 1973 and 2001. In 97 patients there was an element of seminoma in the dissection specimen and/or pure seminoma in the testicular primary specimen (seminoma group). The remaining 1,269 patients underwent post-chemotherapy retroperitoneal lymph node dissection for nonseminomatous testicular tumors. The rates of intraoperative complications and additional procedures as well as postoperative complications were analyzed. RESULTS: Of the 97 patients in the seminoma group 37 (38.1%) required a total of 47 additional intraoperative procedures, including 25 nephrectomies, 9 inferior vena caval resections, 5 arterial grafts, 5 bowel resections and 3 hepatic resections/biopsies, compared with 340 of the 1,269 patients (26.8%) in the group without seminomatous elements (p = 0.02). Postoperatively complications occurred in 24 of 97 patients (24.7%) in the seminoma group versus 257 of 1,269 (20.3%) in the group without seminomatous elements (p = 0.29). One of the 97 patients in the seminoma group died secondary to postoperative complications. CONCLUSIONS: A seminomatous element in patients undergoing post-chemotherapy retroperitoneal lymph node dissection is associated with a higher rate of additional intraoperative procedures and postoperative complications than in patients without seminomatous elements. However, resection is still possible with acceptable morbidity when indicated in appropriately selected patients.

Adolescent↗

Early catheter removal after radical retropubic prostatectomy: long-term followup.

PURPOSE: We examine the complication and continence rates with early catheter removal (day 3 or 4) after radical retropubic prostatectomy. MATERIALS AND METHODS: A total of 365 patients with localized prostate cancer underwent radical retropubic prostatectomy at Indiana University Hospital with planned urethral catheter removal before discharge home. Low pressure cystograms were performed on postoperative day 3 or 4 to determine if catheter removal was possible. A subset of patients were analyzed using a validated prostate cancer specific questionnaire (University of California, Los Angeles Prostate Cancer Symptom Index) to determine quality of life outcomes. RESULTS: The catheter was removed on postoperative day 3 or 4 in 263 patients (72%). The reasons for leaving the catheter indwelling were significant leak on cystogram or excessive suprapubic drainage (21%), extensive bladder neck reconstruction (1%) and prolonged hospitalization because of an ileus or other complicating factor (6%). Thirteen patients (3.6%) were either unable to void after catheter removal or presented with retention (not associated with hematuria or clots) after hospital discharge, requiring reinsertion of the Foley catheter. A total of 41 patients (11%) had either an early or late complication (excluding incontinence). There were 3 complications (0.8%) that were considered major because they were potentially life threatening or required a return to the operating room. A pelvic abscess developed in 2 patients and a lymphocele in 1, which required percutaneous drainage. After at least 6 months (mean 20.9 months) 140 patients (89.2%) and 14 (8.9%) reported excellent and good continence, respectively. The patient questionnaire demonstrated bother scores to be minimal to no bother for 95% to 98% of patients at 6 and 12 months. CONCLUSIONS: This study confirms that it is safe to remove catheters in most patients 3 to 4 days after prostatectomy if a cystogram demonstrates no extravasation. Complication rates and continence rates with this approach compare favorably with series in which catheters are left indwelling for longer periods.

Device Removal↗

Molecular evidence supporting the neoplastic nature of some epidermoid cysts of the testis.

CONTEXT: Loss of heterozygosity (LOH) on chromosomes 9p and 12q is common in germ cell tumors of the testis. Loss of heterozygosity of 17p13 has also been demonstrated in germ cell tumors. The incidence of LOH in epidermoid cysts, a possible special form of teratoma, has not been previously determined. OBJECTIVE: To determine the frequency of LOH in epidermoid cysts. DESIGN: Eight testicular epidermoid cysts and surrounding parenchyma were microdissected from formalin-fixed, paraffin-embedded tissue, and the genomic DNA was extracted using proteinase K. Polymerase chain reaction analysis targeted regions on chromosome 9p21 (D9S177 and D9S161 loci), chromosome 12q22 (D12S1051 locus), and chromosome 17p13 (TP53 locus). Gel electrophoresis followed by autoradiography was used to detect LOH. RESULTS: All 8 of the epidermoid cysts were informative at a minimum of 1 of 4 loci. Three demonstrated LOH. In 2 tumors, LOH occurred on chromosome 9, and the third tumor demonstrated LOH on chromosome 12. Loss of heterozygosity on chromosome 17p13 was not present in any of the tumors. CONCLUSIONS: Epidermoid cysts harbor allelic loss at some of the same loci identified in malignant testicular germ cell tumors. Our findings support that some examples of epidermoid cysts are neoplastic, although their low frequency of LOH also supports that they are genetically different from malignant germ cell tumors.

Chromosomes, Human, Pair 12↗

Teratoma in the orchiectomy specimen and volume of metastasis are predictors of retroperitoneal teratoma in post-chemotherapy nonseminomatous testis cancer.

PURPOSE: Patients who require post-chemotherapy retroperitoneal lymph node dissection after induction chemotherapy for metastatic testis cancer derive therapeutic benefit from resection of teratoma but resection of necrosis is not beneficial. We determine if the absence of teratoma in the orchiectomy specimen is a reliable predictor of the absence of teratoma in the retroperitoneum at post-chemotherapy retroperitoneal lymph node dissection. MATERIALS AND METHODS: A retrospective review of the Indiana University testis cancer data base was performed. A total of 644 patients who underwent retroperitoneal lymph node dissection after induction chemotherapy only were selected for study. The presence or absence of teratoma in the orchiectomy specimen and volume of retroperitoneal tumor were analyzed as predictors of retroperitoneal teratoma at post-chemotherapy retroperitoneal lymph node dissection. RESULTS: Of the patients with teratoma in the orchiectomy specimen 85.6% had an element of teratoma in the retroperitoneum, and of those without teratomatous elements in the orchiectomy specimen 48% had teratoma in the retroperitoneum (p <0.00001). Increasing volumes of retroperitoneal tumor were associated with a higher probability of discovering teratoma at post-chemotherapy retroperitoneal lymph node dissection. CONCLUSIONS: The absence of teratoma in the orchiectomy specimen does not reliably predict the absence of teratoma in the surgical specimen at post-chemotherapy retroperitoneal lymph node dissection. Post-chemotherapy surgery is indicated if retroperitoneal tumor remains after chemotherapy irrespective of the presence or absence of teratoma in the orchiectomy specimen.

Chemotherapy, Adjuvant↗

Pathologic findings and therapeutic outcome of desperation post-chemotherapy retroperitoneal lymph node dissection in advanced germ cell cancer.

Increased serum tumor markers after cisplatin-based chemotherapy have usually been considered a contraindication to surgery because of the presence of persistent active germ cell elements. However, a select population of patients with elevated serum tumor markers have undergone post-chemotherapy retroperitoneal lymph node dissection (RPLND) with curative intent. We evaluated the role of surgery to resect retroperitoneal-only marker positive tumor. Long-term survival was observed in 50% of patients. Residual germ cell cancer was identified in 50% of patients, with a third alive at 5 years with no observed benefit from adjuvant chemotherapy. Select patients with increased tumor markers after chemotherapy are cured with surgery.

Biomarkers, Tumor↗