Reuse of carboplatin and paclitaxel in patients with relapsed endometrial cancer--the British Columbia Cancer Agency experience

ObjectiveTo evaluate the efficacy of reusing carboplatin and taxol in women with relapsed endometrial cancer.MethodsRetrospective analysis of our database of newly diagnosed high-risk patients with endometrial cancer treated with carboplatin–paclitaxel at diagnosis, with subsequent relapse for the period of 1995–2007.Results111 patients of 200 relapsed. They had either endometroid or papillary serous histologies. Strategies utilized upon first relapse were: no treatment (n = 33), surgery (n = 4), hormones (n = 8), irradiation (n = 14) and chemotherapy (n = 52). Carboplatin and paclitaxel was reused in 31 (60% of 52 retreated with chemotherapy or 29% of the total cohort of 111). There was no statistically significant difference in stage at diagnosis or grade at diagnosis between those retreated with chemotherapy or not or with carboplatin–paclitaxel versus another regimen. The patients retreated were a selected subgroup as only those with initial response or treated adjuvantly were offered carboplatin–paclitaxel. CR or PR were achieved in 8 (42%) patients with endometroid type cancer. In the papillary serous group 6 (50%) had CR or PR. Median PFS from first relapse was 8 months for endometroid and 9 months for papillary serous histology. OS was 15 months and 26 months respectively from first relapse.ConclusionCarboplatin–taxol regimen is an efficacious treatment. Due to the patient selection these outcomes reported are likely to be an overstatement of what could be achieved in practice.     

Asparaginase-like protein 1 is an independent prognostic marker in primary endometrial cancer,and is frequently lost in metastatic lesions

Objective

Loss of Asparaginase-like protein 1 (ASRGL1) has been suggested as a prognostic biomarker in endometrial carcinoma. Our objective was to validate this in a prospectively collected, independent patient cohort, and evaluate ASRGL1 expression in endometrial carcinoma precursor lesion and metastases.

Sentinel lymph node biopsy in early-stage cervical cancer: utility of intraoperative versus postoperative assessment

ObjectiveTo determine the diagnostic accuracy of sentinel lymph node (SLN) detection using lymphoscintigraphy, intraoperative blue dye, and radiocolloid in patients with early-stage cervical cancer.MethodsIntra-cervical injection of technetium-99 sulfur colloid and lymphoscintigraphy were performed preoperatively. Isosulfan blue was injected intra-cervically immediately prior to surgery. SLNs were excised and examined intraoperatively (imprint cytology and frozen section) and postoperatively (H and E histology and immunohistochemistry (IHC) for cytokeratin).ResultsThirty eight patients were evaluable. Laparoscopy and laparotomy were performed in 28.9% and 71.1%, respectively. Subjects had squamous cell carcinoma (n = 26), adenocarcinoma (n = 10) or adenosquamous (n = 2) histologies. 55.3% had cervical tumors < 2 cm. The overall SLN detection rate was 92.1%. The external iliac region just distal to the common iliac bifurcation was the most common SLN location. A mean of 2.1 SLNs were detected per patient with bilateral SLNs observed in 47.4%. On final pathology, metastatic nodal disease was identified in 15.7% of patients. Of these, 83.3% were detected in the SLNs. Sensitivity of SLN detection of metastasis was 100% for patients with cervical tumors < 2 cm. However intraoperative evaluation by imprint cytology and frozen section correctly identified lymph node metastasis in only 33.3%.ConclusionsSLN detection is feasible and accurately reflects pelvic nodal basin status when performed in early-stage cervical cancer patients. However, while current intraoperative pathology techniques for assessing nodal metastases reliably detect metastases larger than 2 mm, they lack sufficient sensitivity to detect micrometastasis and isolated tumor cells.     

Risk factors for poor prognosis in microinvasive adenocarcinoma of the uterine cervix (IA1 and IA2): a pooled analysis

ObjectiveTo identify adverse risk factors for FIGO IA1 and IA2 cervical adenocarcinoma.MethodsPubMed was used to identify all microinvasive adenocarcinoma cases. Case specific data pooled for 35 “high risk” microinvasive adenocarcinoma (MIAC), defined as cases with lymph node or lymphovascular space involvement, positive surgical margins, or recurrence was compared with 478 “low risk” cases abstracted from the SEER database (1988–1997). Statistical methods included non-paired t and Fisher's Exact tests.ResultsSurvival for 1A1 and 1A2 MIAC is 99% and 98%, respectively. Significantly more 1A2 patients underwent aggressive radical surgery and received postoperative treatment. Parametrial involvement was rare (1/373 cases). Significantly more “high-risk” cases were of endometrioid histology (6/34 vs. 14/478, p = 0.001), whereas adenocarcinoma (p = 0.046) and mucinous (p = 0.021) tumors were observed in the “low-risk” group. Among the “high-risk” cases with at least 5 years follow-up, 1.4% has recurred or died.ConclusionsEndometrioid histology may be associated with late recurrence and worse survival in stage 1A1 and 1A2 MIAC.     

Adjuvant radiation for early stage endometrial cancer with lymphovascular invasion

ObjectiveTo determine the impact of the decrease in use of postoperative pelvic external beam radiation (EBRT) in favor of intravaginal RT (IVRT) alone in patients with early stage endometrial cancer who had lymphovascular invasion (LVI).MethodsBetween 11/1988 and 5/2005, 126 patients treated with simple hysterectomy and postoperative RT had a final pathologic diagnosis of stage IB–IIB adenocarcinoma of endometrioid histology with documented LVI. The patients were divided into two groups based on the era of treatment, (early era: 1988–1996, vs. late era: 1997–2005), in order to best capture the shift away from the routine use of EBRT in favor of surgical staging and IVRT.ResultsOf the 126 patients, 35% (n = 44) were treated in the early era and 65% (n = 82) in the late era. The two groups were balanced in regards to age, race, depth of myometrial invasion, histologic grade, and cervical involvement. Significantly more patients had surgical staging and received IVRT alone in the late than early era (p = 0.0001, 0.004, respectively). The rate of pelvic control was 93% for the early era compared to 97% for latter era (p = 0.3). There was no significant impact of the treatment era on vaginal control, disease-free survival, or overall survival.ConclusionsThese data suggest that the mere presence of LVI need not trigger the use of pelvic EBRT. Instead, the decision on whether to omit EBRT in patients with LVI should be made in the context of a patient's competing risk factors and comorbid conditions.     

A phase II trial of carboplatin and docetaxel followed by radiotherapy given in a "Sandwich" method for stage III, IV, and recurrent endometrial cancer

ObjectiveTo determine feasibility and efficacy of administering docetaxel and carboplatin chemotherapy followed by pelvic radiotherapy and then consolidation chemotherapy in patients with advanced or recurrent endometrial cancer.MethodsPatients with surgically staged III–IV (excluding IIIA from positive cytology alone) endometrial cancer or biopsy confirmed recurrent disease were eligible. Treatment consisted of 3 cycles of docetaxel (75 mg/m²) and carboplatin (AUC 6) on a q21 day schedule followed by involved field irradiation (45 Gy) ± brachytherapy and three additional cycles of docetaxel and carboplatin. Kaplan–Meier (KM) methods estimated overall survival (OS) and progression free survival (PFS).ResultsForty-two patients enrolled, 7 did not complete therapy. 95% (39/41) had primary disease. Median age = 58 years (range: 21–81 years). 78% (32/41) = endometrioid histology. Stages = 10 IIIA, 21 IIIC, 1 IVA, 7 IVB, (recurrent = 1 IC, 1 IIA). There were 23 non-hematologic and 14 grade 3 and 16 grade 4 hematologic toxicities. Seven patients died following treatment with a median follow-up of 28 months (range: 7–70 months). KM estimates and 95% confidence intervals for OS at 1 year were 95% (82–99%), at 3 years 90% (75–96%), and at 5 years 71% (45–86%). Of the 39 with primary disease, 11 progressed or died within 5 years of study enrollment. KM estimates and 95% confidence intervals for PFS at 1 year were 87% (72–94%), at 3 years 71% (51–83%), and at 5 years 64% (42–80%).Conclusions“Sandwiching” radiation between chemotherapy for advanced or recurrent endometrial cancer merits further development based on the reported PFS and OS.     

Phase II trial of erlotinib in women with squamous cell carcinoma of the vulva

ObjectiveTo evaluate the efficacy and toxicity of erlotinib in the management of squamous cell carcinoma (SCC) of the vulva.MethodsPatients with vulvar lesions amenable to surgery or chemoradiation (cohort 1) or those with metastatic measurable disease (cohort 2) received erlotinib 150 mg daily. Patients were monitored for toxicity. Responses were determined by digital photography or RECIST 1.1. Cohort 1 underwent pre and post treatment biopsies. EGFR immunohistochemistry (IHC), fluorescence in-situ hybridization (FISH), and mutational analysis were performed.Results41 patients were enrolled: 17 in cohort 1 and 24 in cohort 2. Notable grade 3 or 4 toxicities included allergic reaction (1), diarrhea/electrolyte abnormalities (3), ischemic colitis (1), and renal failure (3) and electrolyte abnormalities (n = 2). Mean number of cycles for cohort 2 was 3.3. Overall clinical benefit rate was 67.5% with 11 (27.5%) partial responses (PR), 16 (40.0%) stable disease (SD), and 7 (17.5%) progressive disease. Responses were of short duration. All pre and post treatment biopsies exhibited 2–3 + EGFR staining. 5 of 14 patients (35%) were found to have EGFR amplification (n = 3) or high polysomy/trisomy (n = 2). These five patients had either a PR (n = 3) or SD (n = 2). Gain of function mutations were not been identified.ConclusionsThis is the first reported controlled trial evaluating erlotinib for the management of vulvar carcinoma. Toxicities were acceptable given the lack of treatment options for these patients. Given the observed clinical benefits erlotinib may represent one of the most active agents available to treat vulvar SCC.     

Treatment results of endometrial hyperplasia after prospective D-score classification: a follow-up study comparing effect of LNG-IUD and oral progestins versus observation only

ObjectivesThree different treatment options for endometrial hyperplasia were evaluated in a prospective long-time follow-up study, comparing effects of intrauterine levonorgestrel impregnated device (LNG-IUD), low oral dose of medroxyprogesterone acetate (MPA) and no treatment (observation only). To select patients with high probability for co-existing or future carcinoma we used the objective morphometric algorithm, D-score, stratifying patients into three different risk groups. As far as we know, this is the first prospective long-time follow-up study in which treatment recommendation and outcome is based on the D-score assessment.MethodsFrom a total of 370 patients initially diagnosed with endometrial hyperplasia from eight different hospitals in North Norway, 258 were available for long-time follow-up. After D-score classification, one of three different treatment options was chosen: LNG-IUD, low oral dose of MPA or observation only. Follow-up controls were performed and biopsies taken in the local hospitals.ResultsAmong the 370 investigated cases with endometrial hyperplasia, only ten endometrial cancers were detected at the entrance of the study, all belonging to the high risk group (D-score < 0). No further cancers were detected during follow-up, irrespective of risk group. After 6 months treatment with LNG-IUD proved significantly superior to oral treatment (p = 0.001 for D-score > 1and p = 0.003 for D-score 0–1 groups) and observation only (p = 0.001 for D-score > 1 and p = 0.001 for D-score 0–1 groups). After 56 to 108 months the LNG-IUD proved significantly superior to oral treatment and to the observation group. Comparison of oral therapy to observation only showed no significant differences, neither after 6 months nor after long-time observation.ConclusionsLNG-IUD is the optimal treatment for endometrial hyperplasia. Outcome after oral low-dose MPA regimen is comparable to expectation.     

Prognostic role of the recepteur d'origine nantais (RON) expression in ovarian cancer patients

ObjectiveThe aim of the study was to investigate the potential clinical relevance of immunohistochemically assessed RON expression in a large, single institution series of primary untreated advanced ovarian cancer patients.MethodsImmunohistochemical analysis was performed by using the polyclonal rabbit anti-RON-β antibody (C-20, clone sc-322, Santa Cruz, California). Results were expressed as the total proportion of immunostained tumor cells (RON positivity), or the percentage of cells showing strong staining of RON expression (H-RON positivity).ResultsIn the overall series RON positive immunoreaction was observed in 103/141 cases, while H-Ron positivity was detected in 577141 (40.4%) cases. No association between RON and H-RON expression with response to first-line treatment was documented. During the follow up period, progression and death of disease were observed in 111 (78.7%) and 76 (53.9%) cases, respectively. Cases with strong H-RON expression has a shorter overall survival (median = 35 months) than cases with low RON levels (median = 59 months) (X² = ? 2.1, p value = 0.032). In multivariate analysis, only platinum resistance, and extent of residual tumor retained an independent negative prognostic role for OS, with the percentages of H-RON positively immunostained cells showing a borderline statistical significance (p value = 0.0643). The unfavourable role of elevated percentages of H-RON expression was maintained only in the subgroup of platinum resistant recurrent ovarian cancer patients (X² = 3.89, p value = 0.048) compared to the platinum sensitive ones (X² = 1.98, p value = 0.16).ConclusionsThe assessment of RON expression deserves further attention as a parameter helpful to identify poor prognosis ovarian cancer patients potentially candidates to investigational agents.     

DNA hypermethylation, Her-2/neu overexpression and p53 mutations in ovarian carcinoma

ObjectivesTo define patterns of aberrant DNA methylation, p53 mutation and Her-2/neu overexpression in tissues from benign (n = 29), malignant (n = 100), and border line malignant ovaries (n = 10), as compared to normal (n = 68) ovarian tissues. Further, to explore the relationship between the presence of genetic and epigenetic abnormalities in ovarian cancers, and assess the association between epigenetic changes and clinical stage of malignancy at presentation and response to therapy.MethodsThe methylation status of 23 genes that were previously reported associated with various epithelial malignancies was assessed in normal and abnormal ovarian tissues by methylation-specific PCR. The presence of p53 mutation (n = 82 cases) and Her-2/neu overexpression (n = 51 cases) were assessed by DNA sequencing and immunohistochemistry, respectively.ResultsMethylation of four genes (MINT31, HIC1, RASSF1, and CABIN1) was significantly associated with ovarian cancer but not other ovarian pathology. Her-2/neu overexpression was associated with aberrant methylation of three genes (MINT31, RASSF1, and CDH13), although aberrant methylation was not associated with p53 mutations. Methylation of RASSF1 and HIC1 was more frequent in early compared to late stage ovarian cancer, while methylation of CABIN1 and RASSF1 was associated with response to chemotherapy.ConclusionDNA methylation of tumor suppressor genes is a frequent event in ovarian cancer, and in some cases is associated with Her-2/neu overexpression. Methylation of CABIN1 and RASSF1 may have the utility to predict response to therapy.     

Risk factors for a serous cancer precursor ("p53 signature") in women with inherited BRCA mutations

ObjectivesPelvic (ovarian) serous carcinomas frequently contain p53 mutations. Recently, a candidate serous cancer precursor (the p53 signature) with p53 mutations and other features in common with serous cancer has been discovered in distal fallopian tube mucosa. This study examined the relationship of putative ovarian cancer risk factors with the presence of p53 signatures in women with BRCA mutations (BRCA+).MethodsFallopian tubes from 75 BRCA+ women were immunostained for p53 signatures and correlated with age at first childbirth, parity, oral contraceptive use, body mass index (BMI), and BRCA subtype (1 or 2). Statistical analysis was performed with the T-test or Chi-square analysis and logistic regression adjusting for age and parity.ResultsThirty-eight percent of the tubes contained p53 signatures, which were significantly associated with older age at first childbirth (mean 30.8 vs. 28.4 years; p = 0.04) and lower parity (mean 1.4 vs. 2.2; p = 0.01) in univariate analyses. The unadjusted odds ratios were 3.8 (p-trend = 0.04) for first childbirth ≥ 30 years versus < 30 and 0.2 (p-trend = 0.01) for parity ≥ 3 versus nulliparous women. After adjusting for age and parity, the trend for age at first childbirth became non-significant (adjusted odds ratio 3.5; p-trend = 0.15), while that for parity remained significant (adjusted odds ratio 0.2; p-trend 0.02).ConclusionsThe p53 signature is significantly associated with lower parity and possibly higher age at first childbirth, further linking this entity to serous cancer via risk factors associated with ovulation. The p53 signature merits consideration as a surrogate marker for serous cancer risk.     

Twenty-year review of radiotherapy for vaginal cancer: an institutional experience

ObjectiveTo evaluate clinical outcome, prognostic factors and chronic morbidity with radiotherapy for vaginal cancer treatment.Materials and methods68 patients with vaginal cancer treated by radical or adjuvant radiotherapy (RT) were selected. Five with rare subtypes of histopathology and 8 with adenocarcinoma were excluded from this study. 76.4% of the remainder had early-stage diseases (stage I: 14, II: 28, III: 9, and IV: 4). The patients in the years from which they were treated were almost evenly distributed (1st 5 years: 13, 2nd: 14, 3rd: 16, and 4th: 12). There were four treatment groups: external beam radiotherapy (EBRT) alone (n = 18), brachytherapy (BT) alone (n = 4), EBRT and BT (n = 30), and surgery plus RT (n = 3).ResultsMedian follow-up was 50.3 months ranging from 3 to 213 months. 5-year overall survival (OS) was 55.6%, disease-specific survival (DSS) was 77.3%, disease-free survival was 74.2%, and local control was 87.7%. Independent prognostic factors for DSS and OS were tumor stage, site and size (p < 0.05). Late radiation toxicity was minimal in the bladder (4.6%) and bowel (4.6%). Vaginal morbidity was observed in 35 patients (63.6%). It was lowest in the BT alone (0%), and highest in the EBRT and BT group (82.1%), especially for those received more than 70 Gy (p = 0.05, Odds ratio = 4.64, 95% confidence interval: 1.01–21.65).ConclusionThis retrospective review suggested that tumor stage, site, and size were important prognostic factors in patients with vaginal cancer. Higher radiation dose was associated with more frequent vaginal toxicity.     

High-throughput interrogation of PIK3CA,PTEN, KRAS,FBXW7 and TP53 mutations in primary endometrial carcinoma

ObjectiveEndometrial cancer patients may benefit from systemic adjuvant chemotherapy, alone or in combination with targeted therapies. Prognostic and predictive markers are needed, however, to identify patients amenable for these therapies.MethodsPrimary endometrial tumors were genotyped for > 100 hot spot mutations in genes potentially acting as prognostic or predictive markers. Mutations were correlated with tumor characteristics in a discovery cohort, replicated in independent cohorts and finally, confirmed in the overall population (n = 1063).ResultsPIK3CA, PTEN and KRAS mutations were most frequently detected, respectively in 172 (16.2%), 164 (15.4%) and 161 (15.1%) tumors. Binary logistic regression revealed that PIK3CA mutations were more common in high-grade tumors (OR = 2.03; P = 0.001 for grade 2 and OR = 1.89; P = 0.012 for grade 3 compared to grade 1), whereas a positive TP53 status correlated with type II tumors (OR = 11.92; P < 0.001) and PTEN mutations with type I tumors (OR = 19.58; P = 0.003). Conversely, FBXW7 mutations correlated with positive lymph nodes (OR = 3.38; P = 0.045). When assessing the effects of individual hot spot mutations, the H1047R mutation in PIK3CA correlated with high tumor grade and reduced relapse-free survival (HR = 2.18; P = 0.028).ConclusionsMutations in PIK3CA, TP53, PTEN and FBXW7 correlate with high tumor grade, endometrial cancer type and lymph node status, whereas PIK3CA H1047R mutations serve as prognostic markers for relapse-free survival in endometrial cancer patients.     

What is the optimal minimally invasive surgical procedure for endometrial cancer staging in the obese and morbidly obese woman?

ObjectiveThirty-three percent of U.S. women are either obese or morbidly obese. This is associated with an increased risk of death from all causes and is also associated with an increased risk of endometrial carcinoma. We sought to compare minimally invasive surgical techniques for staging the obese and morbidly obese woman with endometrial cancer.Materials and methodsConsecutive robotic endometrial cancer staging procedures were collected from 2005–2007 and were compared to consecutive laparoscopic cases (2000–2004). Demographics including age, weight, body mass index (BMI), operative time, estimated blood loss, lymph node retrieval, hospital stay and complications were collected and compared.ResultsDuring the study period, there were 36 obese and 13 morbidly obese women who underwent surgery with the DaVinci® robotic system and 25 obese and 7 morbidly obese women who underwent traditional laparoscopy. For both the obese and morbidly obese patient, robotic surgery was associated with shorter operative time (p = 0.0004), less blood loss (p < 0.0001), increased lymph node retrieval (p = 0.004) and shorter hospital stay (p = 0.0119).ConclusionsRobotic surgery is a useful minimally invasive tool for the comprehensive surgical staging of the obese and morbidly obese woman with endometrial cancer. As this patient population is at increased risk of death from all causes, including post-operative complications, all efforts should be made to improve their outcomes and minimally invasive surgery provides a useful platform by which this can occur.     

An overview of a 30-year experience with amniocentesis in a single tertiary medical center in Taiwan

ObjectiveAmniocentesis is a popular and effective prenatal diagnostic tool for chromosomal disorders. It is well-established that the risk of chromosomal abnormalities increases with maternal age; however, other related indications are seldom reported. Herein, we report our 30-year experience with amniocentesis from a single medical center, focusing on the indications and rates of abnormality.Material and MethodsA retrospective review of 16,749 pregnant women in the mid-trimester between January 1981 and December 2010 was conducted. The medical records were analyzed.ResultsThe indications for amniocentesis were advanced maternal age (≥ 34 years old) (n = 10,970, 65.5%), increasing-risk maternal triple-marker Down's screening test (≥ 1/270) (n = 2090, 12.5%), history of abnormal offspring birth (n = 792, 4.7%), abnormal ultrasound findings (n = 484, 2.9%), parent with abnormal karyotype (n = 252, 1.5%), family history of chromosomal abnormality (n = 183, 1.1%), drug and radiation exposure (n = 165), abnormal chorionic villus sampling (CVS) results (n = 25), intrauterine fetal death (n = 50), and other non-specific causes (n = 1662, 9.9%). The rate of abnormality for each indication was 16% in the abnormal CVS group, 12% in the intrauterine fetal death group, 11.5% for parental chromosomal abnormality, 8.7% in the abnormal ultrasound finding group, 3.0% in the increasing-risk maternal triple-marker Down's screening test group, 2.5% in the advanced maternal age group, 1.5% for other non-specific causes, 1.4% for history of abnormal offspring birth, and 1.1% for family history of chromosomal abnormality.ConclusionsBoth parents with abnormal karyotype and abnormal ultrasound findings are indications for which consideration of further amniocentesis is highly recommended.     

The utility and cost effectiveness of preoperative computed tomography for patients with uterine malignancies

ObjectiveTo determine the utility and cost effectiveness of preoperative computed tomography (CT) in detecting disease extent in patients with uterine carcinoma.MethodsMedical records of 762 patients with uterine malignancies at hysterectomy from 1990–2006 were reviewed. Study inclusion required preoperative abdominal-pelvic CT scan. All CT findings were correlated with intraoperative and pathologic data. Statistical analysis was performed using Fisher's exact test. Cost analysis was based on Medicare fee schedules.Results250 subjects (33%), who underwent preoperative CT, comprised the study cohort. CT suggested metastases in 22 (9%) cases and altered management in 7 (3%). Incidental findings were noted in 43 cases (17%), and altered management in 7 (3%). Among complex atypical hyperplasia (CAH) and grade 1 endometrioid cancers, CT suggested metastases in 9% and demonstrated other incidental findings in 21%; management was altered in just 4% of patients. Similarly, among grade 2/3 endometrioid tumors, CT suggested metastases in 7%, and incidental findings in 14%; management was altered in 4% of cases. For high-risk histologies, CT altered management in 11% of papillary serous and clear cell cases and in 13% of sarcomas. CT findings more often altered management in women with high-risk histologies than in those with endometrioid carcinomas (p = 0.05). Expenditure of $17,622 for CT imaging is required to alter management of one patient.ConclusionsPreoperative CT is costly, and rarely alters management in patients with uterine neoplasms, particularly among endometrioid carcinomas. CT may be beneficial in patients with high-risk histologies and requires further study.     

Combined chemotherapy and radiation improves survival for node-positive endometrial cancer

ObjectiveTo evaluate the clinical outcomes for women with node-positive endometrioid adenocarcinoma of the uterusMethodsRecords were reviewed for 66 patients with Stage IIIC endometrioid adenocarcinoma diagnosed between 1/1995 and 12/2009. Study inclusion required TAH, BSO and negative chest imaging. Papillary serous and clear cell histologies were excluded. Adjuvant treatment was external beam radiation (RT) alone in 18 patients (27%), combined chemotherapy and RT in 44 (67%), chemotherapy alone in 1 (2%), and no adjuvant therapy in 3 (5%). The median follow-up was 48 months.ResultsOf 66 patients, 56 (85%) had positive pelvic nodes only, 5 (8%) had positive para-aortic nodes only, and 5 (8%) had both. Of the 62 patients who received adjuvant RT, only 4 (6%) had an in-field recurrence, including 2 with residual disease after surgery. Disease-free (DFS) and overall (OS) survival rates at 5 years were 71% and 81%, respectively. By adjuvant treatment modality, 5-year DFS and OS rates were 63% and 67% for RT alone and 79% and 90% for combined modality therapy (p = 0.15 and p < 0.01). On multivariate analysis, combined modality therapy significantly improved DFS (HR 0.12, 95% CI 0.03–0.49, p < 0.01) and OS (HR 0.20, 95% CI 0.05–0.75, p = 0.02) compared to adjuvant RT alone.ConclusionsCompared to RT alone, combined modality therapy decreased recurrence and improved survival in patients with node-positive endometrioid adenocarcinoma of the uterus. In addition, external beam RT resulted in excellent local and regional control. Future studies are needed to define the optimal chemotherapy regimen, sequencing, and radiation fields.     

Galactose-1-Phosphate Uridyl Transferase Deficiency Is Not Associated with Müllerian Aplasia in Dutch Patients

Study ObjectiveTo study whether a deficiency in galactose-1-phosphate uridyl transferase (GALT) activity of mothers was an explanation for the occurrence of Müllerian aplasia of their daughters.DesignA case control study.SettingThe patients were selected from the outpatient clinic of the University Medical Center Nijmegen, and compared with the general population in The Netherlands.ParticipantsPatients (n = 9) diagnosed with the syndrome of Müllerian aplasia and their mothers were included.InterventionsA questionnaire for medical and family history was taken, and a venous blood sample and urine were collected.Main Outcome MeasuresGALT activity (in blood), galactose and galactilol (in urine) were measured. Measured values were analyzed by Student's paired t-test.ResultsAll patients and their mothers had normal GALT activities ≥ 20 μmol/h/g Hb. The mean value did not differ from the mean of the normal Dutch population, which was 31.6 (SD = 5.0) μmol/h/g Hb.ConclusionGALT deficiency is not an explanation for Müllerian aplasia, at least in the Dutch population.     

Differential expression of WT1 and p53 in serous and endometrioid carcinomas of the endometrium.

Wilms' tumor antibody (WT1) has recently been reported to be reactive in most ovarian and peritoneal serous carcinomas, but few studies have looked at WT1 reactivity in endometrial carcinomas. p53, like WT1, is a tumor suppressor gene and in its mutated form is frequently present in endometrial serous carcinoma. Routine immunohistochemical staining for p53 and WT1 was performed in 70 endometrial carcinomas (39 endometrioid and 31 serous) of varying differentiation using tissue microarrays. Only 2 (7.5%) serous carcinomas and none of the endometrioid carcinomas (0%) were reactive for WT1. p53 immunoreactivity was found in 26 (83.9%) serous carcinomas and in 2 (5.1%) endometrioid carcinomas. We conclude that WT1 and p53 expression are not related and that WT1 expression in endometrial serous carcinoma differs from that of its extrauterine counterparts.     

Comparison of misoprostol-only and combined mifepristone-misoprostol regimens for home-based early medical abortion in Tunisia and Vietnam

ObjectiveTo assess the potential advantages of combined mifepristone–misoprostol versus misoprostol-only for early medical abortion.MethodsA double-blind randomized placebo controlled study was conducted that enrolled 441 pregnant women (< 63 days since last menstrual period) at 2 hospitals in Tunisia and Vietnam. The mifepristone–misoprostol group (n = 220) received 200 mg of mifepristone on day 1 and 800 μg buccal misoprostol followed by placebo 3 hours later on day 2. The misoprostol-only group (n = 221) received placebo on day 1 and 1600 μg of misoprostol (2 doses of 800 μg, given 3 hours apart) on day 2. All medications were self-administered at home with follow-up 1 week later. The primary outcome was complete uterine evacuation without surgical intervention.ResultsSuccessful uterine evacuation occurred for 78.0% (n = 170) of women with misoprostol only versus 92.9% (n = 195) of women with mifepristone–misoprostol (relative risk 0.84, 95% CI, 0.78–0.91; P < 0.001). Ongoing pregnancy occurred for 13.8% (n = 30) of women given misoprostol-only and 1.4% (n = 3) of women given mifepristone–misoprostol (relative risk 9.63, 95% CI 2.98–31.09; P < 0.001).ConclusionMifepristone plus misoprostol is significantly more effective than misoprostol-only for early medical abortion.Clinical trials.gov registration number: NCT00680394.