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Biomedical subjects

J O Schorge

Publications and source records attributed to J O Schorge.

At least 19 recordsLinked to original sources
PubMed2001

Multimodality therapy in early-stage neuroendocrine carcinoma of the uterine cervix.

OBJECTIVE: Patients with early-stage neuroendocrine cervical carcinoma (NECC) have a high mortality rate despite aggressive therapy. The rarity of this tumor precludes initiation of a randomized, prospective trial. We reviewed our experience in early stage disease and performed a meta-analysis of the literature to identify prognostic factors and determine optimal multimodality therapy. METHODS: Eleven women with International Federation of Gynecology and Obstetrics (FIGO) early stage (IB--IIA) NECC were treated with surgery and chemotherapy at our institutions between 1978 and 1998. Administration of radiation therapy was recorded, but not required for inclusion in this study. A gynecologic pathologist reviewed all histopathologic sections. Medical records were retrospectively reviewed and clinical data obtained. Twenty-three early-stage NECC patients who were similarly treated during the study interval were identified by a Medline search of the English literature and included in the analysis. The Kaplan--Meier method and log-rank test were used for survival analysis. RESULTS: The overall 2-year survival rate for the 34 patients was 38%. The median age was 37 years (range, 20--75 years). Median cervical tumor diameter was 3.2 cm (range 0.5--11.0 cm). Lymphovascular space invasion was present in 21 (78%) of 27 patients (7 unknown). Fifteen (52%) of twenty-nine had lymph node metastases (5 unknown). Fifteen patients received postoperative platinum/etoposide (PE), seven received vincristine/adriamycin/cyclophosphamide (VAC), two received alternating cycles of VAC and PE, and ten received other chemotherapy regimens. Twenty women were treated with radiation therapy. The presence of lymph node metastases was a poor prognostic factor (P < 0.001). PE and VAC chemotherapy was associated with increased survival (P < 0.01). CONCLUSION: NECC is a highly lethal variant of cervical cancer. The presence of lymph node metastases is the most important prognostic variable. Postoperative VAC or PE appears most likely to improve chances for survival.

Adult↗
PubMed2001

Germline BRCA1-2 mutations in non-Ashkenazi families with double primary breast and ovarian cancer.

OBJECTIVE: Ashkenazi women with double primary breast and ovarian cancer have a high prevalence (57%) of germline Jewish founder mutations in the BRCA1 (185delAG, 5382insC) and BRCA2 (6174delT) genes. The purpose of this study was to determine the frequency and type of BRCA1-2 mutations in non-Ashkenazi families with at least one member having double primary breast and ovarian cancer. METHODS: Women at increased risk for cancer based upon their family history were enrolled at the University of Texas Southwestern Familial Cancer Registry between 1992 and 2000. Blood samples from patients desiring genetic testing were sent for complete DNA sequencing of the BRCA1 and BRCA2 genes. Families with a member having both breast and ovarian cancer were identified and clinical data were obtained. RESULTS: Sixty-two (7%) of 900 enrolled families were non-Ashkenazi and had at least one member with double primary breast and ovarian cancer. Twenty-one families had members who underwent genetic testing; 41 did not. Thirteen (62%) families had a germline BRCA1 (n = 11) or BRCA2 (n = 2) mutation; only one Jewish founder mutation (185delAG) was detected. Eight (38%) families tested negative. Six (86%) of seven women undergoing genetic testing who themselves had double primary breast and ovarian cancer were BRCA1-2 mutation carriers. CONCLUSIONS: Germline BRCA1-2 mutations are common in non-Ashkenazi families with a member having double primary breast and ovarian cancer. These mutations occurred throughout both genes, emphasizing the need for comprehensive sequencing. One family had the BRCA2 6985delCT mutation, which lies beyond the "ovarian cancer cluster" region.

Adult↗
PubMed2000

BRCA1-related papillary serous carcinoma of the peritoneum has a unique molecular pathogenesis.

Papillary serous carcinoma of the peritoneum (PSCP) is believed to develop de novo from the peritoneal lining of the pelvis and abdomen. Although it is histologically indistinguishable from serous ovarian carcinoma, PSCP exhibits minimal or absent ovarian involvement and may even develop in a woman years after prophylactic oophorectomy. We have shown previously that patients with germ-line BRCA1 mutations who develop PSCP are more likely to have disease originating from multiple peritoneal sites compared with patients with wild-type BRCA1. In this study, we tested the hypothesis that BRCA1-related PSCP has a unique molecular pathogenesis. DNA was extracted from normal tissue and multiple tumor sites in patients with PSCP. BRCA1 and p53 gene mutations were screened for using single-strand conformation polymorphism. Loss of heterozygosity was determined at the BRCA1 and p53 loci. Immunohistochemical analyses of p53, epidermal growth factor receptor, erbB-2, erbB-3, erbB-4, and Bcl-2 expression were performed. We detected germ-line BRCA1 mutations in 11 (26%) of 43 PSCP patients. BRCA1 mutation carriers had a higher overall incidence of p53 mutations (89% versus 47%; P = 0.052), were more likely to exhibit multifocal or null p53 mutations (63% versus 7%; P = 0.014), and were less likely to exhibit erbB-2 overexpression (P = 0.013) than wild-type BRCA1 case subjects. We propose that the unique molecular pathogenesis of BRCA1-related PSCP may affect the ability of current methods to reliably prevent or detect this disease prior to metastasis.

BRCA1 Protein↗
PubMed2000

Genetic alterations of the WT1 gene in papillary serous carcinoma of the peritoneum.

OBJECTIVE: The Wilms' tumor (WT1) gene product is consistently detectable in both normal ovarian germinal epithelium and human mesothelium. Ovarian carcinomas frequently exhibit alterations in WT1 function. Papillary serous carcinoma of the peritoneum (PSCP) is believed to develop de novo from the peritoneal lining (mesothelium) of the pelvis and abdomen. The purpose of this study was to determine if genetic alterations of the WT1 gene are associated with the development of PSCP. METHODS: Normal and tumor tissue specimens were retrieved from patients with stage III and IV PSCP (n = 38) and serous epithelial ovarian carcinoma (n = 38). Immunohistochemistry was performed using the anti-WT1 (C-19) antibody. Loss of heterozygosity (LOH) was performed at the WT1 locus. Clinical data were obtained and correlated with molecular findings. RESULTS: Loss of normal WT1 expression was detected in 18 (51%) of 35 PSCP specimens and 18 (53%) of 34 ovarian carcinoma specimens. Six (27%) of 22 PSCP specimens and 3 (13%) of 24 ovarian carcinoma specimens had LOH at the WT1 locus (P = 0.27). Normal WT1 gene expression was maintained in 86% of tumors exhibiting LOH. Genetic alterations of the WT1 gene were not predictive of survival, nor were they associated with other clinical or molecular factors. CONCLUSIONS: Genetic alterations of the WT1 gene are associated with the development of PSCP. The loss of normal WT1 gene expression is a common event in both PSCP and advanced ovarian carcinoma, likely resulting from down-regulation by other regulatory factors-not from inactivating gene mutation and subsequent allelic loss.

Adult↗
PubMed2000

Prospective management of stage IA(1) cervical adenocarcinoma by conization alone to preserve fertility: a preliminary report.

OBJECTIVE: Microinvasive cervical adenocarcinoma has an excellent prognosis and emerging data support the hypothesis that it should be treated in the same way as its squamous counterpart. We report our preliminary experience prospectively treating stage IA(1) cervical adenocarcinoma by conization alone in women who strongly desired to preserve their fertility. METHODS: Since May 1998, all patients with stage IA(1) cervical adenocarcinoma who expressed a strong desire to preserve fertility have been offered cold knife conization (CKC) and careful surveillance without hysterectomy. Women with lesions identifiable only microscopically, up to 3 mm invasive depth, up to 7 mm tumor width, and a conization specimen including the entire lesion with negative margins were eligible for conservative management. Postconization surveillance consisted of a Pap smear and endocervical curettage every 4 months. Medical records were reviewed for clinical data, follow-up, and disease status. RESULTS: Five women ages 26-33 elected CKC and surveillance. Four were nulliparous and one primiparous. Four tumors were endocervical cell type; one was adenosquamous. Three were grade 1, one was grade 2, and one grade 3. None had lymph-vascular space invasion. None of the patients has developed recurrent disease after 6-20 months of follow-up. CONCLUSIONS: Our preliminary data suggest that patients with FIGO stage IA(1) cervical adenocarcinoma who strongly desire to preserve their fertility may be treated by conization alone if they are fully informed of the unknown risks for disease recurrence and are carefully followed. A multicenter trial is the next logical step to test the efficacy of this approach.

Adenocarcinoma↗
PubMed2000

Conservative management of adenocarcinoma in situ of the cervix.

OBJECTIVE: The purpose of this study was to determine the method of treatment and outcome of women with cervical adenocarcinoma in situ (AIS). METHODS: Following institutional review board approval, all women diagnosed with cervical AIS from 1987 to 1999 were identified. Data were retrospectively collected by record review and correspondence with medical providers. RESULTS: Of 132 women treated with cone biopsy for AIS, 95 (72%) were managed conservatively after cold knife cone or loop electrical excisional procedure alone; 37 (28%) eventually underwent hysterectomy. The median age of diagnosis was 29 years (range, 17-47) in the conservative management group and 40 years (range, 25-72) in the hysterectomy group (P < 0.0001). Seventy-four percent were nulliparous in the conservative group compared with 27% in the hysterectomy group (P < 0.0001). Of the 95 conservatively managed patients, 92 obtained negative margins; three were followed despite positive or unevaluable margins. During a median follow-up of 30 months, 9 women required evaluation for follow-up abnormalities after cone biopsy with negative margins. None had pathologic evidence of recurrent AIS. Twenty-three infants were delivered. Hysterectomy was generally performed for undesired fertility or persistently positive cone margins. One woman required hysterectomy for recurrent AIS. Thirteen (62%) of twenty-one hysterectomy specimens had residual AIS following cone biopsy with positive or unevaluable margins; 1 (6%) of 16 had residual AIS following cone biopsy with negative margins (P < 0.0001). No patient developed invasive adenocarcinoma. CONCLUSIONS: Younger women with cervical AIS may be effectively treated with cone biopsy alone if negative margins can be achieved.

Adenocarcinoma↗
PubMed2000

Gestational trophoblastic disease.

Patients diagnosed with molar pregnancy are treated by either suction curettage or hysterectomy, depending on their desire to preserve fertility. We use single-agent chemotherapy, preferably methotrexate, to treat low- or moderate-risk persistent trophoblastic tumors. High-risk patients who have metastatic disease are treated primarily with combination chemotherapy and, as indicated, adjuvant radiotherapy or surgery. We perform a hysterectomy in all cases of placental-site trophoblastic tumors; combination chemotherapy is used if there is evidence of metastatic disease.

Adult↗
PubMed2000

Bcl-2 and p53 protein expression, apoptosis, and p53 mutation in human epithelial ovarian cancers.

Bcl-2 and p53 gene products have been both linked to cell death by apoptosis. In the present study, we examined the relationship of Bcl-2 and p53 protein expression, p53 mutation and apoptosis in normal human ovaries and different types of human ovarian epithelial tumors by immunohistochemical localization, in situ terminal transferase-mediated dUTP nick end labeling and polymerase chain reaction-single strand conformation polymorphism. It was found that Bcl-2 expressed strongly in the surface epithelium of normal ovaries and benign and borderline ovarian tumors but weakly in the malignant tumors. On the contrary, strong protein expression of p53 was found in 54% (25/46) of the malignant epithelial tumors examined but similar expression of p53 was not observed in borderline and benign tumors and normal ovarian surface epithelium. A significant inverse correlation between Bcl-2 and p53 expression was found in the malignant ovarian tumors examined. p53 gene mutation at exons 5-11 was however not a pre-requisite for p53 expression in both borderline and malignant tumors. Apoptotic activities, as reflected by apoptotic indices, were low in normal ovarian surface epithelium and benign tumors but were increased in borderline and malignant tumors, with the highest average apoptotic index found in grade III malignant tumors. Statistical analyses showed a positive correlation between apoptosis and p53 expression, but similar correlation was not found between apoptosis and Bcl-2 expression. Our results also indicate that although expression of Bcl-2 is important during ovarian carcinogenesis, the Bcl-2 protein may have other roles to play apart from being a modulator of apoptosis in human ovarian epithelial cancers.

Apoptosis↗
PubMed2000

Distinct allelic loss patterns in papillary serous carcinoma of the peritoneum.

Tumor and normal tissues from 55 patients with papillary serous carcinoma of the peritoneum (PSCP) were analyzed. Polymerase chain reaction amplification of tandem repeat polymorphism was used to screen for loss of heterozygosity (LOH). We mapped 22 oligonucleotide primers to chromosomes 1p, 3p, 6q, 7q, 9p, 11p, 17p, 17q, and Xq. Germline BRCA1 mutation status of 43 patients was determined previously. High frequencies (> 30%) of LOH in PSCP were observed on 6q, 9p, 17p, 17q, and Xq. Compared with allelic loss of serous epithelial ovarian carcinoma (SEOC), the frequency of LOH was significantly lower in PSCP on 1p, 7q, 11p, 17p, and 17q. Of 43 cases screened for germline BRCA1 mutations, 9 cases were identified with mutations. The frequencies of LOH were not significantly different among the BRCA1-related and BRCA1-unrelated PSCP cases. The high LOH rate identified on 6q, 9p, 17p, 17q, and Xq in PSCP suggests that candidate tumor suppressor genes residing in these regions may be important for the development of the tumor. Compared with allelic loss of SEOC, PSCP exhibits a significantly lower frequency of LOH on chromosomes 1p36, 7q31.3, 11p15.1, 17p13.1, and 17q21. An increase in susceptibility to the acquisition of allelic loss in BRCA1-related PSCP cannot be identified.

Alleles↗
PubMed2000

Recent advances in gestational trophoblastic disease.

Recent advances have increased our understanding of gestational trophoblastic disease, and epidemiologic studies have demonstrated that there are important differences in risk factors for complete and partial mole. Complete moles are now increasingly being diagnosed in the first trimester, affecting their clinical presentation and pathologic characteristics. While important advances have been made in chemotherapy, it is now recognized that etoposide is associated with a risk of second tumors. Several studies have advanced understanding of the molecular biology of gestational trophoblastic disease, and this is important for the eventual development of new and innovative therapy.

Antineoplastic Agents↗
PubMed1999

Stage IA1 cervical adenocarcinoma: definition and treatment.

OBJECTIVE: To propose a definition for stage IA1 cervical adenocarcinoma, based on the International Federation of Gynecology and Obstetrics (FIGO) staging system, and to determine if patients meeting criteria might be candidates for conservative surgery. METHODS: Two hundred women were diagnosed with early-stage cervical adenocarcinoma from 1982 to 1996. Histopathologic sections were reviewed by a gynecologic pathologist. Medical records were reviewed, and patients included in this study had microscopically identifiable lesions, up to 3 mm invasive depth, up to 7 mm tumor width, and negative margins if cone biopsy was performed. RESULTS: Twenty-one patients with microinvasive adenocarcinoma met criteria for FIGO stage IA1 carcinoma of the cervix. The median (range) follow-up was 76 (30-172) months and median (range) patient age was 38 (24-75) years. Definitive treatment included type II or III radical hysterectomy in 16 cases, simple abdominal or vaginal hysterectomy in four cases, and loop electrosurgical excision procedure in one case; one patient received adjuvant pelvic radiation. The histologic subtypes were endocervical adenocarcinoma in 18 cases, adenosquamous carcinoma in two cases, and clear-cell adenocarcinoma in one case. There was no evidence of parametrial invasion or lymph node metastases in any patient who had radical surgery, and there were no disease recurrences. CONCLUSION: Patients with microinvasive adenocarcinoma who met criteria for FIGO stage IA1 cervical carcinoma had disease limited to the cervix, and conservative surgery, such as cone biopsy or simple hysterectomy, might offer them definitive treatment.

Adenocarcinoma↗
PubMed1999

Early cervical adenocarcinoma: selection criteria for radical surgery.

OBJECTIVE: To identify selection criteria for radical surgery in early cervical adenocarcinoma based on pretreatment clinical stage and correlation with high-risk surgical-pathologic factors. METHODS: One hundred seventy-five women with International Federation of Gynecology and Obstetrics (FIGO) clinical stage IB1 (n = 132) and IB2-IIA (n = 43) cervical adenocarcinoma were treated primarily at our institutions from 1982 to 1996. Histopathologic sections were reviewed by a gynecologic pathologist. Medical records were reviewed retrospectively and clinical follow-up was done. RESULTS: The overall 5-year survival rate was 87% (95% confidence interval [CI] 81%, 93%) for stage IB1 and 61% (95% CI 46%, 77%) for stage IB2-IIA (P<.001). Adenosquamous cell type, deep cervical invasion, and lymph-vascular space invasion were significant independent high-risk surgical-pathologic factors that affected disease-free survival (each P<.002). One hundred fourteen (86%) of 132 stage IB1 patients and 19 (44%) of 43 stage IB2-IIA subjects were treated primarily with radical surgery. Lymph node metastases, lymph-vascular space invasion, adenosquamous cell type, deep cervical invasion, and positive surgical margins were more than twice as frequent in stage IB2-IIA patients who had radical surgery than in stage IB1 patients (each P <.05). Based on high-risk surgical-pathologic factors in 133 subjects who had radical surgery, postoperative radiotherapy was recommended for 18 (16%) of 114 stage IB1 patients and 18 (95%) of 19 stage IB2-IIA subjects (P<.001). CONCLUSION: Radical surgery for FIGO clinical stage IB1 cervical adenocarcinoma and primary radiotherapy for stage IB2-IIA disease would largely avoid combined-modality therapy, thereby reducing treatment-related toxicity and cost.

Adenocarcinoma↗
PubMed1999

Clinically significant venous thromboembolism after gynecologic surgery.

OBJECTIVE: To review the incidence and outcome of clinically significant venous thromboembolism (VTE) following gynecologic surgery in a population receiving provider-specified prophylaxis. STUDY DESIGN: A computerized patient database was used to identify all patients diagnosed with VTE following gynecologic surgery from 1992 to 1997. Medical records were retrospectively reviewed. Clinically significant postoperative VTE was defined as pulmonary embolism or deep venous thrombosis, suggested by symptoms and physical findings, with subsequent confirmation by appropriate imaging study. Patients having VTE at the time of preoperative hospital admission and patients diagnosed with VTE after postoperative day 30 were excluded. RESULTS: Fifty-three patients developed postoperative VTE after > 30,000 gynecologic surgical procedures (incidence, < 1 event per 500 procedures). Forty-eight (91%) patients received some form of prophylaxis. Patients with benign disease, surgical anesthesia less than three hours and no history of prior VTE or factor V Leiden deficiency rarely developed postoperative VTE (incidence, < 1 event in 4,000 procedures). Thirteen (25%) patients had complications from anticoagulation therapy requiring prolonged hospital stay or readmission. CONCLUSION: Clinically significant VTE following gynecologic surgery is rare in the absence of malignancy, prolonged surgical anesthesia or hypercoagulation factors. Complications from anticoagulation therapy are common among gynecologic patients undergoing treatment for VTE.

Adult↗
PubMed1998

Molecular evidence for multifocal papillary serous carcinoma of the peritoneum in patients with germline BRCA1 mutations.

BACKGROUND: Papillary serous carcinoma of the peritoneum (PSCP) diffusely involves peritoneal surfaces, while it spares or only superficially involves the ovaries. PSCP is histologically indistinguishable from serous epithelial ovarian carcinoma, and it may develop years after oophorectomy. The molecular pathogenesis of PSCP remains unresolved, although preliminary data suggest a multifocal origin in some cases. Patients with germline BRCA1 mutations may develop PSCP in addition to breast and ovarian carcinomas. The purpose of this study was to utilize the androgen receptor (AR) gene locus to test the hypothesis that some cases of PSCP have a multifocal origin and to determine if patients with germline BRCA1 mutations develop multifocal PSCP. METHODS: Specimens of normal and tumor tissues from 22 women with PSCP were obtained, and DNA was extracted. The AR gene locus was evaluated for patterns of loss of heterozygosity (LOH) and X-chromosome inactivation. The methylation-sensitive Hpa II restriction enzyme was used to differentiate the active and inactive X chromosomes. Germline BRCA1 mutation status of the patients was determined previously. RESULTS: Genetic analysis of tumor specimens indicated that five (23%) of 22 case subjects had patterns of selective LOH at the AR locus, consistent with multifocal, polyclonal disease origin. Two patients with selective LOH also had alternating X-chromosome inactivation patterns. Patients with germline BRCA1 mutations were more likely to have evidence of multifocal disease (two-sided Fisher's exact test, P = .01). CONCLUSIONS: Our results show that PSCP has a multifocal origin in at least some cases. Furthermore, patients with germline BRCA1 mutations are more likely to develop multifocal PSCP than are patients without BRCA1 mutations.

Adult↗
PubMed1998

BRCA1 gene mutations in women with papillary serous carcinoma of the peritoneum.

OBJECTIVE: To compare BRCA1 mutations in papillary serous carcinoma of the peritoneum and papillary serous ovarian carcinoma. METHODS: Germline DNA from 17 consecutive patients with peritoneal carcinoma was screened for mutations in the BRCA1 gene using single-strand conformation polymorphism analysis. Shifted DNA bands were sequenced. Patients with germline BRCA1 mutations were screened for allelic loss in tumor DNA at the BRCA1 locus. RESULTS: Two of the 17 patients (11%, 95% confidence interval 0.07, 0.37) exhibited the 185 delAG germline BRCA1 mutation described in the Ashkenazi Jewish population. The family history of one patient was notable for a mother and five aunts with breast or ovarian cancer. The other patient had a personal history of breast cancer. Both patients exhibited allelic loss of the normal BRCA1 allele in their tumor. A third patient was found to have a previously undescribed exon 11 single base pair substitution at nucleotide 1239 (CAG to CAC) resulting in a missense mutation (Gln to His). The patient had no family or personal history of breast or ovarian cancer, and her tumor did not exhibit loss of heterozygosity. CONCLUSION: Germline BRCA1 mutations occur in papillary serous carcinoma of the peritoneum with a frequency comparable to the BRCA1 mutation rate in ovarian cancer. Although the penetrance is unknown, peritoneal carcinoma should be considered a malignancy expressed in the familial breast ovarian cancer syndrome.

Cystadenocarcinoma, Papillary↗
PubMed1998

Postpartum and vulvar necrotizing fasciitis. Early clinical diagnosis and histopathologic correlation.

OBJECTIVE: To review the clinical course and correlate histopathologic findings of obstetrics and gynecology patients with necrotizing fasciitis STUDY DESIGN: Seven-teen patients with postpartum or vulvar necrotizing fasciitis were identified from 1981 to 1996. Medical records were retrospectively reviewed. Information was available for all patients until death or discharge from the hospital. Histopathologic material on 15 patients was available for review. RESULTS: Five postpartum patients were diagnosed and surgically debrided one to nine days after cesarean delivery, with no mortality. Twelve patients with vulvar necrotizing fasciitis were diagnosed and surgically debrided <1-10 days after presentation to a physician, with three deaths (25%). On histopathologic review, all cases had prominent lobular and septal panniculitis. Thirteen cases had histologic evidence of fasciitis. CONCLUSION: Early diagnosis and aggressive surgical debridement in patients with postpartum and vulvar necrotizing fasciitis may improve the outcome. Histopathologic findings are remarkably consistent and may help to confirm the diagnosis.

Adult↗