Biomedical subjects

Karl C Podratz

Publications and source records attributed to Karl C Podratz.

At least 37 records · Page 2Linked to original sources

PubMed2005

Ovarian remnant syndrome.

OBJECTIVE: This study was undertaken to examine surgical management of patients with ovarian remnant syndrome. STUDY DESIGN: Data were abstracted from records of patients with a history of bilateral salpingo-oophorectomy who were treated surgically at Mayo Clinic between 1985 and 2003 for pathologically confirmed residual ovarian tissue. A follow-up questionnaire was also mailed. RESULTS: Records review identified 186 patients (mean age, 37.6 years; mean follow-up, 1.2 years). Of 180 patients with available data, 153 (85%) underwent oophorectomy by laparotomy, 13 (7%) by laparoscopy, and 14 (8%) by transvaginal approach, mostly for endometriosis (56.8%). Of 186 patients, 105 (57%) presented with pelvic masses and 89 (48%) with pelvic pain. Remnant ovarian tissue was associated with a corpus luteum in 78 (42%) and endometriosis in 54 (29%). The intraoperative complication rate was 9.6%. Of 142 patients, 12 (9%) required subsequent re-exploration (1 ovarian remnant identified). CONCLUSION: This heavily pretreated population has modest risk of bowel, bladder, or ureteral trauma with definitive pelvic sidewall stripping and apical vaginal excision. However, subsequent recurrence is minimal (<1%). More than 90% of patients reported resolution or marked improvement of symptoms.

Adult↗

PubMed2005

Overexpression of the TGF-beta antagonist Smad7 in endometrial cancer.

OBJECTIVE: We have shown that HER2/Neu may activate the Smad7 promoter in endometrial, ovarian, and breast cancer cell lines. Elevated Smad7 levels could then antagonize the TGF-beta pathway, leading to a reduction in tumor surveillance and potential cancer formation. Our aim was to determine if Smad7 was in fact overexpressed in endometrial cancers and whether Smad7 RNA levels correlated with tumor grade or clinical endpoints. METHODS: Snap-frozen endometrial cancer specimens from 16 patients with grade 1 disease and 23 patients with grade 3 disease were obtained. Additionally, the endometrium from 18 patients who underwent hysterectomy for benign indications was collected as a control. RNA was extracted and subjected to quantitative real-time PCR to determine the degree of Smad7 RNA expression. Clinical outcomes including time to recurrence were recorded through retrospective chart review. RESULTS: Smad7 transcripts in the tumors were over 11-fold elevated on average than in controls (P < 0.001). There was no significant difference in Smad7 RNA between grades 1 and 3 tumors. For the 19 patients who recurred, median time to recurrence was 56.3 months for those with low Smad7 expression versus 30 months for those with high Smad7 expression (P < 0.004). CONCLUSION: Smad7 appears to be upregulated in endometrial cancers compared to normal endometrium. Furthermore, high Smad7 gene expression was associated with a shorter time to recurrence. Given that many endometrial cancers have been shown to be TGF-beta-unresponsive, Smad7 should be investigated as a potential target to restore TGF-beta responsiveness and limit tumor growth.

Cytoskeletal Proteins↗

PubMed2005

Salvage whole-abdominal radiation therapy after second-look laparotomy or secondary debulking surgery in patients with ovarian cancer.

OBJECTIVES: Our aim was to determine the outcomes associated with use of whole-abdominal radiation therapy (WART) in women with ovarian cancer, to identify predictors of response, and to assess associated toxicity. METHODS: From 1981 through 2000, 171 women received WART at our institution after ovarian cancer surgery. Relevant clinical information was extracted through retrospective chart review. RESULTS: One hundred nine patients received WART after positive second-look laparotomy (SLL), and 62 were treated after secondary debulking (SD) for recurrent disease. The median dose to the whole abdomen was 25.5 Gy (range, 1.0-30.5 Gy). Therapy included a pelvic boost in 120 patients (70%) and a para-aortic boost in 21 patients (12%). The planned radiation course was completed in 123 patients (72%). In the SLL group, 5-year survival was 29% with a median follow-up of 98.4 months. The 5-year progression-free survival (PFS) was 41% in those with microscopic disease. There was one treatment-related death (1%). For the SD group, median PFS was 11 months and associated with treatment-related mortality in 5%. Overall, treatment-related small bowel obstruction occurred in 26 patients (15%). CONCLUSIONS: In patients with a positive SLL, WART should be considered only for those with microscopic residual disease. Treatment-related small bowel obstruction can be expected in 15% of these patients. Use of WART for recurrent disease appears to be related to serious bowel toxicity in 5% with an associated short disease-free interval; the therapeutic index of WART may not be acceptable in patients with recurrent disease regardless of the degree of cytoreduction.

Combined Modality Therapy↗

PubMed2005

Up-regulation of DNA methyltransferase 3B expression in endometrial cancers.

OBJECTIVE: To understand the role of epigenetic regulation in the pathogenesis of endometrial cancer, we have characterized DNA methyltransferase 3B (DNMT3B) gene expression in normal, Grade I and Grade III endometrioid cancers, and examined DNMT3B promoter activities in endometrial cancer cell lines. METHODS: DNMT3B expression was measured in normal, Grade I, and Grade III endometrioid cancer samples. Real-time PCR and Western blot analysis were performed to compare DNMT3B mRNA and protein levels. DNMT3B levels were also compared among endometrial cell lines including those for Ishikawa, KLE, AN3, RL-95, HEC-1A, and HEC-1B. DNMT3B promoter reporter plasmids were constructed. Promoter activities in well and poorly differentiated cell lines were compared by in vitro reporter gene transfection. RESULTS: DNMT3B was significantly up-regulated in both Grade I and Grade III cancers as compared to normal controls. Western blot analysis confirmed the increased DNMT3B protein expression in cancer tissues. It was also found that the well-differentiated endometrial cell line, Ishikawa, expressed lower levels of DNMT3B than the poorly differentiated KLE cells, the expression patterns similar to those observed in tumor specimens. CONCLUSION: The results suggest that DNMT3B overexpression may play a significant role in endometrial cancer development. In addition, the transfection experiments indicated that DNMT3B promoters are more active in the poorly differentiated endometrial cancer cell lines, suggesting that the in vitro assay provides a useful model for studying the DNMT3B transactivation mechanism related to tumor transformation.

Carcinoma, Endometrioid↗

PubMed2005

Endometrial cancer: can nodal status be predicted with curettage?

OBJECTIVE: To determine whether histologic or molecular markers assessed in pretreatment curettage specimens predict nodal metastasis in endometrial cancer. METHODS: Phenotypic and molecular variables (ploidy, proliferating cell nuclear antigen, MIB-1, p53, HER-2/neu, and bcl-2) were analyzed in preoperative specimens from 82 patients with endometrial cancer who had lymph nodes dissected. These 82 patients had been selected from a total population of 283 patients with endometrial cancer, using a case-cohort design. Weighted logistic regressions were then used to determine significant predictors of positive lymph nodes, and results were estimated for the total population of 283 patients. RESULTS: Of the overall population, 12% of patients were estimated to have positive lymph nodes. Histologic subtype, p53, and bcl-2 each were significantly correlated (P <0.05) with lymph node status. With application of stepwise logistic regression, p53 was the only independent predictor of lymph node status. In addition, a statistical model predictive of positive lymph nodes was generated which incorporated the risk factors p53, bcl-2, and histologic subtype. CONCLUSION: In pretreatment curettage specimens, the presence of unfavorable levels of p53 or bcl-2 or of nonendometrioid histologic features, or combinations of those, significantly predicted lymph node status, thus facilitating the preoperative identification of patients at risk of lymph node metastases.

Adult↗

PubMed2005

Opposite alterations of DNA methyltransferase gene expression in endometrioid and serous endometrial cancers.

OBJECTIVE: To examine the DNA methyltransferase (DNMT) mRNA and protein levels in endometrioid and serous cancers and to study the relationship between DNA methyltransferase expression and endometrial cancer development. METHODS: Normal endometrium, Grade I and Grade III endometrioid carcinoma tissues and cell lines, as well as serous cancer tissues, were analyzed for DNMT expression. Real-time PCR and Western blot techniques were employed to measure the mRNA and protein levels of the four DNA methyltransferases, DNMT1, DNMT2, DNMT3A, and DNMT3B. Immunohistochemistry was performed to detect alterations in DNMT nuclear localization and spatial organization patterns. RESULTS: While DNMT2 and DNMT3A expression appear to be normal, two- to fourfold increase in DNMT1 and DNMT3B were found in both Grade I and Grade III endometrioid cancers. In addition, the poorly differentiated cell lines expressed relatively higher DNMT levels than well-differentiated cells. In contrast to endometrioid carcinomas, serous cancers expressed substantially lower levels of DNMT1 and DNMT3B than normal controls, with four- and twofold reduction observed in DNMT1 and DNMT3B mRNA levels, respectively. Western blot analysis confirmed opposite expression patterns of DNMT1 and DNMT3B protein in endometrioid and serous cancers. Immunohistochemistry showed normal nuclear localization of DNMT1 and DNMT3B in Type I and Type II cancer specimens as well as cell cultures. CONCLUSION: Two opposite DNMT expression patterns were identified in endometrioid and serous cancers. The concerted upregulation in maintenance and de novo DNA methyltransferases in endometrioid carcinomas is consistent with a tendency for gene-specific hypermethylation observed in this histologic subtype, and may be implicated in tumor suppressor silencing. In contrast, the downregulation of maintenance and de novo DNA methyltransferases in serous cancers suggests that these tumors may contain hypomethylated genomic DNA, which has been associated with a higher mutation rate and is consistent with the known pathogenesis of serous-specific phenotypes. Taken together, the data suggest that divergent DNA methylation pathways may be implicated in the development of Type I and Type II endometrial cancers.

Carcinoma, Endometrioid↗

PubMed2005

Long-term survival and disease recurrence in patients with primary squamous cell carcinoma of the vulva.

OBJECTIVES: To assess time to failure and sites of failure with extended follow-up of patients with squamous cell carcinoma (SCC) of the vulva. METHODS: A retrospective analysis of 330 patients with primary SCC of the vulva treated at Mayo Clinic between 1955 and 1990 was conducted. The main outcome measures were the rates of treatment failure. The Kaplan-Meier method and the log-rank test were used to estimate the rates of overall survival, disease-free survival, and recurrence. The Cox proportional hazards model was used to assess independent variables as prognostic factors for treatment failure. RESULTS: All 330 patients in the cohort underwent lymphadenectomy; 113 patients (34.2%) had involvement of the inguinofemoral nodes and 88 patients (26.7%) had treatment failure. Treatment failures occurred more frequently in patients who presented with inguinal metastasis at the primary surgery and during the first 2 years of follow-up. After 2 years, both groups, with or without positive inguinal nodes, had similar treatment failure rates. Most patients with disease recurrence in the groin died within the first 2 years of follow-up. Involvement of the inguinal nodes was the main independent predictive factor for survival, disease recurrence, and metastasis. CONCLUSIONS: Most treatment failures occurred during the 2 years after initial surgical management. However, in 35% of patients, disease reoccurred 5 years or more after diagnosis, which demonstrates the need for long-term follow-up. Complete ipsilateral or bilateral inguinofemoral lymph node dissection ensures a thorough evaluation and treatment of the groin.

Carcinoma, Squamous Cell↗

PubMed2005

Predictors of vaginal relapse in stage I endometrial cancer.

OBJECTIVE: To identify factors predictive of vaginal relapse in stage I endometrial cancer, thereby potentially facilitating the selection of patients who may benefit from vaginal brachytherapy. METHODS: The study population included 632 patients with stage I endometrial cancer managed with hysterectomy at our institution between 1984 and 1996. Median follow-up was 73 months; 122 patients (19%) received adjuvant radiotherapy. RESULTS: Overall, 2.9% of the stage I cohort developed vaginal relapse at 5 years. Vaginal relapse was observed in 1.7% of patients who received radiotherapy and in 3.0% of those whose treatment did not include radiotherapy (P = 0.36). Cox regression analysis (including radiotherapy) identified only grade 3 differentiation (hazard ratio = 3.83, P = 0.007) as an independent predictor of vaginal relapse. Patients with a low-grade tumor had a 5-year vaginal relapse rate of 2%, compared with 7% for those with a grade 3 tumor. When only patients who did not receive adjuvant radiotherapy were considered, both grade 3 tumor and lymphovascular invasion were significant predictors of vaginal relapse (P < 0.05). When neither variable was present, 2% of patients experienced vaginal relapse at 5 years, compared with 11% when either 1 was present (P < 0.001). Depth of myometrial invasion was not a significant predictor of vaginal recurrence. CONCLUSION: Histologic grade 3 tumor and lymphovascular invasion were the cogent predictors of vaginal relapse in our population. The cost and morbidity of vaginal brachytherapy should be balanced against the potential risk of vaginal relapse in this group of patients.

Cohort Studies↗

PubMed2005

Epigenetic-mediated upregulation of progesterone receptor B gene in endometrial cancer cell lines.

OBJECTIVES: To determine if epigenetic interference can restore progesterone receptor-B (PR-B) expression in PR-B negative endometrial adenocarcinoma cell lines, and to characterize the kinetics of PR-B induction mediated by DNA methyltransferase and histone deacetylase inhibitors. METHODS: The PR-B negative endometrioid cancer cell lines KLE and HEC-1B were used as study models. PR-B mRNA and protein expression levels were measured using real-time PCR and Western blot analysis, respectively. DNA methylation levels of the PR-B promoter were determined by methylation-specific PCR. Dose-response correlations and the duration of response to aza-deoxycytidine (ADC) and trichostatin A (TSA) were characterized. Cell responses to prolonged and repeated drug treatment were also examined. RESULTS: Relatively low concentrations of ADC and TSA over a 24-h period induced PR-B expression. Furthermore, ADC and TSA acted synergistically to reactivate PR-B expression. Depending on the cell line used, PR-B mRNA was induced 10-110 fold. This elevated PR-B expression continued for 48 h after drug withdrawal. Sustained upregulation of PR-B mRNA and protein was observed during prolonged and repeated drug treatment. CONCLUSION: The epigenetically silenced PR-B gene remains sensitive to changes in DNA demethylation and histone acetylation in uterine adenocarcinoma cell lines. Treatment with ADC and/or TSA results in a robust and sustainable PR-B upregulation. These small molecule epigenetic modifying agents may be used to sensitize poorly differentiated, PR-B negative endometrial cancers to progestational therapy.

Adenocarcinoma↗

PubMed2005

Biallelic methylation and silencing of paternally expressed gene 3 (PEG3) in gynecologic cancer cell lines.

OBJECTIVE: To measure mRNA expression levels of paternally expressed gene 3 (PEG3) in gynecologic cancer cell lines and to determine if DNA methylation is involved in the control of PEG3 expression. METHODS: PEG3 mRNA levels were measured with real-time PCR from 28 gynecologic cancer cell lines and compared to normal tissues. PEG3 mRNA expression was correlated to promoter methylation levels measured by real-time methylation-specific PCR. Polymorphism-specific restriction digestion was employed to analyze PEG3 allele distribution. RESULTS: While expressed in normal gynecologic tissues, PEG3 is silenced in all endometrial and cervical cancer cell lines studied. In the eight ovarian cancer cell lines, five were found to be PEG3 negative, the remaining three express low levels of PEG3 mRNA. In contrast, loss of maternal imprinting and relatively high PEG3 expression levels were detected in all four choriocarcinomas cell lines studied. No cell line confirmed to contain two copies of PEG3 expressed PEG3 mRNA, suggesting that PEG3 downregulation is not due to genetic deletion. PEG3 mRNA expression was, however, quantitatively correlated to its promoter methylation status. Treatment of PEG3 negative cells with DNA methyltransferase inhibitor 5'-aza-deoxycytidine led to partial promoter demethylation and biallelic reactivation of PEG3 transcription, confirming the methylation-mediated mechanism for PEG3 silencing. CONCLUSION: PEG3 silencing is associated with DNA hypermethylation but not gene deletion in cell lines tested. These results suggest that loss of PEG3 expression may be a frequent event in gynecologic cancers. Given the known role of PEG3 in p53-mediated apoptosis, it is possible that PEG3 functions as a tumor suppressor.

Alleles↗

PubMed2005

Soluble epidermal growth factor receptor (sEGFR) [corrected] and cancer antigen 125 (CA125) as screening and diagnostic tests for epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) is the leading cause of death among all gynecologic cancers in the United States. Because women who are diagnosed with early stage disease have a better prognosis than women diagnosed with late stage disease, early detection represents a potentially practical approach to reduce the mortality associated with EOC. Unfortunately, no single screening test has proven to be effective for this purpose, and a valid and feasible screening program to detect early stage EOC in the general population has not yet been devised. Consequently, research has focused on coupling two or more screening modalities to improve program validity and feasibility. Serum cancer antigen 125 (CA125) and a soluble isoform of the epidermal growth factor receptor (p110 sEGFR) have been studied individually as biomarkers of ovarian cancer. In this study, we compare serum CA125 levels and sEGFR concentrations in women with EOC to women with benign gynecologic conditions of ovarian and non-ovarian origin. We show that serum sEGFR concentrations are lower in patients with EOC than in women with benign gynecologic conditions, whereas serum CA125 levels are higher in patients to EOC compared with women with benign gynecologic conditions. These data also reveal that age and serum sEGFR concentrations modify the association between CA125 levels and EOC versus benign gynecologic disease. Hence, age- and sEGFR-dependent CA125 cutoff thresholds improve the ability of CA125 to discern EOC patients from women with benign ovarian tumors and non-ovarian gynecologic conditions. Our analyses show that parallel testing with fixed sEGFR and CA125 cutoff thresholds optimizes sensitivity to detect EOC, whereas serial testing with age- and sEGFR-dependent CA125 cutoff thresholds optimizes test specificity, and overall accuracy to discern patients with EOC from women with benign ovarian and non-ovarian gynecologic conditions. The combined use of serologic sEGFR and CA125, thus, has improved utility for screening and diagnosing EOC, which may increase the positive predictive value of a multimodal screening program that incorporates these biomarkers to detect and subsequently differentiate benign from malignant ovarian tumors.

Adult↗

PubMed2004

Endometrial carcinoma: paraaortic dissemination.

OBJECTIVE: The objective of our study was to identify pathologic factors predictive of tumor dissemination to paraaortic lymph nodes (LNs) in endometrial carcinoma. The identification of the risk factors may potentially facilitate selection of patients for radical surgery or radiotherapy directed to the paraaortic area (PAA). METHODS: The study population was a cohort from 612 consecutive patients with endometrial cancer surgically managed at our institution over a 10-year period. Tumor dissemination to the PAA was identified by selecting those patients who had either paraaortic LNs positive for disease at the time of primary surgery or those who subsequently experienced paraaortic failure or both (n=41; the "PA mets" subgroup). Therefore, patients for whom no information was available about the status of paraaortic LNs but who had received adjuvant irradiation to the PAA and those for whom information was not available about sites of recurrent disease were excluded from the analysis, leaving 566 patients to compose the study population. RESULTS: On the basis of univariate analysis, numerous pathologic variables were significantly (P< or =0.01) associated with PA mets. However, logistic regression analysis identified only two independent factors predictive of PA mets: positive pelvic LNs (P<0.001, OR=5.00) and lymphovascular invasion (LVI) (P=0.01, OR=1.99). Notably, only 2% of patients with negative pelvic LNs had PA mets compared with 47% of those with positive pelvic LNs (P<0.001). When both pelvic LNs and LVI were negative, only 0.8% of the patients had PA mets compared with 31% of patients for whom at least one of the two variables was positive (P<0.001). CONCLUSION: Positive pelvic LNs and LVI identify a subgroup of high-risk patients (approximately one sixth of the overall population) who potentially may benefit from formal lymphadenectomy or adjuvant therapy or both directed to the PAA. Furthermore, with 47% of patients with positive pelvic LNs having PA mets, unstaged patients at risk for pelvic LN involvement should be considered candidates for both pelvic and paraaortic external beam radiotherapy or surgical restaging.

Adult↗

PubMed2004

Diaphragm resection for ovarian cancer: technique and short-term complications.

OBJECTIVE: Diaphragm resection (DR) is occasionally necessary to achieve optimal cytoreductive surgery in ovarian carcinoma (OC). In a recent survey of the SGO membership, bulky diaphragm disease was one of the most common justifications for suboptimal debulking (Gynecol. Oncol. 82 (2001) 489). The aim of this study was to assess postoperative complications of DR in OC. METHODS: Retrospective chart review of all patients with OC who underwent DR from January 1988 through December 2001 at Mayo Clinic. RESULTS: We identified 41 women who underwent DR for OC. DR was performed during debulking for recurrent disease in 85%. Most patients (95%) underwent associated radical debulking procedures including bowel resection (51%), hepatic resection (27%), and splenectomy (17%). Full-thickness diaphragmatic lesions were present in 85% of specimens. Residual disease was classified as no gross residual in 80% of cases and <1 cm in 10%. Postoperative complications requiring treatment occurred in eight cases: pneumothorax (two cases, definitely attributable to DR); symptomatic pleural effusion (four cases, possibly attributable to DR); one case each of subphrenic abscess and gastro-pleural fistula (most likely unrelated to DR). CONCLUSIONS: (1) DR as part of cytoreductive surgery for ovarian cancer carries comparable risks to other radical debulking procedures. (2) The majority of complications are expected outcomes after entrance into the pleural cavity and generally manageable with chest tube. (3) DR is a useful adjunct to other radical debulking procedures and can eliminate isolated bulky diaphragmatic disease as an obstacle to optimal cytoreductive surgery for patients with ovarian cancer.

Adult↗

PubMed2004

High-risk endometrial cancer subgroups: candidates for target-based adjuvant therapy.

OBJECTIVE: To identify patients with endometrial cancer at risk for hematogenous, lymphatic, or peritoneal recurrence (or combinations of them) who might potentially benefit from target-based therapies. METHODS: During a 13-year period, 915 patients had endometrial cancer managed with hysterectomy and standard adjuvant therapy. On the basis of our previous regression analyses, depth of myometrial invasion predicted the risk for hematogenous recurrence; positive lymph nodes and cervical stromal invasion predicted lymphatic recurrence; stage IV disease or combination of nonendometrioid histology, cervical stromal invasion, positive lymph nodes, and positive peritoneal cytology was predictive of peritoneal recurrence. Median follow-up was 66 months. RESULTS: Applying the above criteria to the population of 915 patients, 24% were considered at risk for hematogenous recurrence, 18% for lymphatic recurrence, and 16% for peritoneal recurrence. The respective relapse rates at 5 years were 28% for patients who were at risk for hematogenous recurrence, 31% for lymphatic recurrence, and 42% for peritoneal recurrence. This contrasted with less than a 5% recurrence rate in the corresponding subgroups not at risk for relapse (P < 0.001). Collectively, of the 915 patients, 324 (35%) were considered at risk for recurrence in one or more of the above three sites. Overall, 89% of all recurrences were identified in this at-risk group. Importantly, 46% of the patients considered at risk subsequently had recurrence in one or more of the three sites, compared with only 2% of patients not at risk for relapse (P < 0.001). CONCLUSION: Patients at risk for relapse had a 46% probability of experiencing recurrence within 5 years despite management with standard therapy. New target-based algorithms for the 35% of endometrial cancer patients deemed at risk should be incorporated in the development of future prospective multimodality clinical trials predicated on site(s) of recurrence.

Adult↗

PubMed2004

Characteristics of patients with vaginal rupture and evisceration.

OBJECTIVE: To characterize vaginal rupture and evisceration. METHODS: We reviewed medical records (1970-2001) for use of the diagnostic terms "vaginal rupture," "vaginal evisceration," and "ruptured enterocele." RESULTS: Twelve clinical cases were identified. Patients usually presented with pain, vaginal bleeding, and abdominal pressure. In 9 of 12 women, rupture was primarily associated with postmenopausal prolapse and a history of pelvic surgery. Women with a history of abdominal hysterectomy tended to rupture through the vaginal cuff, and those with a history of vaginal hysterectomy tended to rupture through a posterior enterocele. Premenopausal rupture in 1 woman occurred postcoitally and involved the posterior fornix. Prolapse recurrence after repair was limited to 1 woman. CONCLUSIONS: Vaginal rupture and evisceration should be considered in women presenting with acute vaginal bleeding and pelvic pain. Evaluation is especially important in postmenopausal women with a history of pelvic surgery. In some cases, surveillance after pelvic surgery may prevent rupture, evisceration, and incarceration. LEVEL OF EVIDENCE: II-3

Adolescent↗

PubMed2003

Risk of occult inguinofemoral lymph node metastasis from squamous carcinoma of the vulva.

PURPOSE: This study was undertaken to correlate preoperative primary tumor size and American Joint Committee on Cancer and International Federation of Gynecology and Obstetrics categories with the risk of subclinical metastases from squamous carcinoma of the vulva to inguinofemoral nodes in patients with a palpably negative groin preoperatively. METHODS AND MATERIALS: Clinical notes, operative reports, and pathology reports from 1955 to 1990 were reviewed to assign retrospectively 1969 American Joint Committee on Cancer N(0) and N(1) and 1988 International Federation of Gynecology and Obstetrics T categories. RESULTS: Of 446 patients with primary carcinoma of the vulva, 226 had a groin without features indicative of lymph node metastasis. Occult groin node metastases were detected in 15.2%, 30.0%, 24.5%, and 0% of patients with T(1), T(2), T(3), and T(4) cancers, respectively. Subclinical node metastases were found in 7.0%, 22.2%, 26.9%, 34.1%, and 20.0% of patients with primary cancers measuring 1.0 cm or less, 1.1 to 2.0 cm, 2.1 to 3.0 cm, 3.1 to 5.0 cm, and larger than 5 cm, respectively. CONCLUSIONS: Efficacy assessment for elective groin node irradiation and quantitative description of the radiation dose-control relationship for subclinical disease should be based on estimates of the risk of subclinical disease within the target volume. This study may help to assess the effectiveness of current therapies.

Carcinoma, Squamous Cell↗

PubMed2003

Distribution of estrogen receptors alpha and beta mRNA in mouse urogenital tissues and their expression after oophorectomy and estrogen replacement.

Estrogen receptors are present in the urogenital tract. However, little is known about the quantitative distribution of the traditional estrogen receptor (ERalpha) mRNA and the recently identified ERbeta mRNA. By quantitative reverse transcription polymerase chain reaction analysis, the distributions of ERalpha and ERbeta mRNA in mouse urogenital tissues and their expression in selected urogenital tissues after oophorectomy, with or without estrogen replacement, were evaluated. ERalpha mRNA concentrations were higher in the ovary, oviduct, uterus and vagina than in the kidney, ureter or bladder ( P<0.05); ERbeta transcripts were highest in the ovary, oviduct and bladder ( P<0.05). After oophorectomy and estrogen replacement, significant changes were identified in ERalpha and ERbeta mRNA expression. ERalpha and ERbeta mRNA are differentially expressed in mouse urogenital tissues. Oophorectomy and estrogen replacement affect estrogen receptors differently in the bladder, vagina and uterus. These results may explain some tissue-specific responses to estrogen and selective estrogen receptor modulators. The mRNA distributions of estrogen receptors alpha and beta and their expression after oophorectomy, with or without estrogen replacement, differ in mouse urogenital tissues.

Animals↗

PubMed2003

Molecular and histopathologic predictors of distant failure in endometrial cancer.

A case-cohort study was designed to correlate various histopathologic and molecular variables with distant failure in endometrial cancer by analyzing phenotypic and molecular indices in hysterectomy specimens. From an overall population of 283 patients with endometrial cancer, we selected a cohort including all 49 patients who experienced any recurrence and 76 randomly chosen patients without recurrence. Expression of nuclear proliferating cell nuclear antigen (PCNA), MIB-1 (a marker of cell proliferation), and p53 was determined with digital image analysis, and cell membrane HER-2/neu and bcl-2 were quantitated visually. Ploidy and DNA indices were determined with flow cytometry. Overall, 6 immunohistochemical and 11 flow cytometric cases were eliminated because of technical inadequacies. Distant failures were defined as primary recurrences that developed outside the pelvis or vagina. Median follow-up was 91 months. Distant failures occurred in 13% of the patients. Cervical stromal invasion, positive adnexae, myometrial invasion >50%, positive lymph nodes, positive peritoneal cytology, lymphovascular invasion, grade 3 histology, nonendometrioid subtype, p53 >33%, strong HER-2/neu membranous staining, aneuploidy, S-phase fraction > or =9%, proliferative index > or =14%, and DNA index > or =1.5 significantly (P<0.05) predicted distant failures. However, a logistic regression model identified only p53 (OR=43.73; P<0.005), lymphovascular invasion (OR=11.59; P<0.001), and cervical stromal invasion (OR=11.29; P=0.001) as cogent predictors of distant failures. Only 3% of patients without any of these three predictors developed distant failures compared with 36% of those with at least one of the three (P<0.01). Thus, locoregional therapy may be insufficient when at least one of these predictors is present.

Adult↗