Extrauterine Disease Research Articles

Efficacy and prognostic implications of administering adjuvant chemotherapy to patients with endometrial cancer that is confined to the uterus

ObjectiveThe purpose of this study was to determine the value of prognostic factors and to assess the efficacy of adjuvant chemotherapy in patients with endometrial cancer confined to the uterus. Study designPatients surgically stage IB, IC and II endometrial cancer according to the International Federation of Gynecology and Obstetrics were enrolled in this study. Stage IIIA tumors with positive peritoneal cytology, in the absence of other evidence of extra uterine disease, were also included. ResultsOne hundred and sixty-seven patients fulfilled the eligibility criteria and 58 patients (34.7%) underwent combination chemotherapy. Disease recurrence occurred in 10 patients within a median time of 17 months. Histologic grade 3 was an independent prognostic factor for both disease-free and overall survival rates. Fourteen of 23 patients with histologic grade 3 tumors received adjuvant chemotherapy consisting of cyclophosphamide (or etoposide), epirubicin and cisplatin (in 1989–1999) or paclitaxel, pirarubicin and carboplatin (in 2000–2002). The 5-year disease-free and overall survival rates for these individuals was 92.3%, a value significantly higher than those in patients who had not undergone chemotherapy (50.0%). ConclusionsHistologic grade of 3 is an independent prognostic marker in patients with endometrial cancer confined to the uterus and adjuvant chemotherapy might improve the survival rates in these patients.

Adjuvant therapy for patients with stage I papillary serous endometrial cancer

Uterine papillary serous carcinoma (UPSC) is an aggressive variant of endometrial cancer characterized by a high recurrence rate and poor prognosis. Several studies have demonstrated that UPSC has a tendency to manifest with extra-uterine disease, even for tumors which appear to be limited to the endometrium. The data on adjuvant chemotherapy for stage I UPSC are limited, and the available studies are generally under-powered to assess if chemotherapy improves survival. However, we believe that, patients with UPSC should receive complete surgical staging, including omentectomy and peritoneal biopsies, and then until the results of larger series or randomized controlled trials will be available, we feel that combined radiotherapy and chemotherapy is justified for all stage I UPSC.

Long-term conservative therapy for endometrial adenocarcinoma in young women

To evaluate the efficacy and safety of long-term conservative therapy with medroxyprogesterone acetate (MPA) for endometrial carcinoma in young patients who had experienced failure after initial therapy or relapse, we reviewed the clinical and pathologic records of eight patients diagnosed with well-differentiated endometrial adenocarcinoma without myometrial invasion who were treated with MPA for over 6 months because of treatment failure or relapse. The average duration of MPA treatment was 22 months. All patients were followed-up for a mean of 76.5 months. Seven patients responded to initial MPA treatment within a period of 14 months (mean, 7.9 months). All these patients experienced relapse and the mean time to relapse was 11.6 months (range, 4-33 months). All six patients with relapse were treated with additional treatments of MPA, and all but one responded to this treatment within a period of 16 months (mean, 8.0 months). Six patients ultimately underwent hysterectomy. All presented well-differentiated endometrioid adenocarcinomas without extrauterine disease. Three became pregnant and two delivered full-term normal infants. No patient died of the disease. Although lesions are expected to disappear with prolonged MPA treatment, this form of progestin therapy is hazardous because recurrence occurs frequently. Only strictly selected patients should therefore be indicated for long-term MPA treatment and careful evaluation before and after treatment should be performed.

Radical hysterectomy for stage IIB cervical cancer: a review

Patients with stage IIB cervical cancer in some countries in Europe and Asia especially in Japan are usually treated with radical hysterectomy and pelvic lymphadenectomy. Extrauterine diseases, ie, nodal metastases, parametrial invasion, and intraperitoneal spread, can be readily identified. We present the literature review of radical hysterectomy in stage IIB cervical cancer by searching data since 1980 from Medline, and we found that the parametrial involvement of patients in this stage was only 21-55%, the incidence of pelvic node metastases was about 35-45%, and 5-year survival rate was between 55% and 77%. Lymph node metastases and the number of positive nodes were significant prognostic factors of patients in this stage.

Does size matter? Tumor size and morphology as predictors of nodal status and recurrence in endometrial cancer

Objective. To determine whether tumor size or morphology is predictive of extrauterine disease and/or recurrence risk in endometrial cancer and therefore guide decisions about the necessity of complete surgical staging and adjuvant therapy. Methods. All women with surgically treated endometrial carcinoma between 1 January 1990 and 1 January 2000 were eligible. 345 patients were eligible for retrospective chart review. Univariate and multivariate logistic regression models were used to determine the predictors of nodal metastasis and recurrence. Results. As tumor size increased, the risk of nodal metastasis increased. However, a risk of nodal metastasis remained even with small lesions less than or equal to 2 cm (6.3% risk). Patients with tumor size greater than 2 cm had a 26.3% incidence of nodal metastasis. In univariate analysis, the odds ratio (OR) for tumor size as a predictor of extrauterine disease was 1.4 (95% CI 1.2–1.6). In multivariate analysis, tumor size was not statistically significant. Only the lesions greater than or equal to 8 cm confer a risk that approaches previously identified well-known predictors. Tumor size was not found to be a statistically significant predictor of recurrence OR 1.3 (1.0–1.8). Conclusions. Tumor size correlates with extrauterine disease, but it is not an independent prognostic variable. Although the risk of extrauterine disease increases with tumor size, the risk of nodal metastases remains even for those patients with very small tumors, underscoring the need for routine complete surgical staging. Tumor size does not appear to be an independent predictor of recurrence.

Magnetic resonance imaging in gynaecological malignancies

In this article the current and developing roles of magnetic resonance imaging (MRI) in endometrial, cervical and ovarian cancer are reviewed. In endometrial cancer, MRI is used to identify myometrial invasion and extrauterine disease, allowing preoperative surgical planning in women with serious comorbidity. In cervical cancer, MRI has an established role in local staging. By assessing the proximal extension of tumours in young women, MRI determines the feasibility of fertility-preserving surgery. It is also used to plan and administer radiotherapy. This optimises tumour radiation, while limiting unwanted radiation to the bowel and other pelvic organs. In ovarian cancer, MRI is useful in young women as it is superior to ultrasound in diagnosing endometriomas, dermoids and fibroids, which can be misdiagnosed by ultrasound as malignant lesions.

Adjuvant treatment for advanced stage endometrial cancer: Patterns of care and outcomes at a single institution

5133 Background: The prognosis for early stage endometrial cancer is excellent. However, 5-year survival in stage III-IV disease declines to 18–50%. Adjuvant treatment for advanced stage endometrial cancer has traditionally been multimodal utilizing hormonal therapy, radiation, and various chemotherapies. To date, no true standard of care exists. We set out to compare recurrence and mortality rates between advanced stage endometrial cancer patients staged and treated at our institution. Methods: We reviewed medical records of all patients with FIGO stage IIIA-IVB endometrial cancers staged and treated at Washington University between 1998 and 2003. Data on demographics, pathologic diagnoses, treatment, recurrence, and mortality rates was analyzed for overall and progression-free survival. Subgroup analyses on high risk/lower risk histologic subtypes, different treatment strategies, and other prognostic factors were performed. Results: Records were available on 124 patients including 72 with stage III and 52 with stage IV disease. 54 (43.5%) had low risk (grade 1 and 2) cancers while 70 (56.5%) had high risk histologic subtypes. Mean follow-up was 20.5 months. Overall, 54 patients (43.5%) recurred and 45 (36.3%) died. Similar proportions were found even in patients with minimal extrauterine disease. 97 patients received adjuvant treatment, 35% with RT alone, 34% with chemotherapy alone, and 10% with combination chemotherapy and RT. Recurrence rates in each group approached 50%, however, there was a trend toward improved OS in the combination therapy group (83.3% versus 62% with chemotherapy and 67% with RT alone). When stratified by histologic risk, survival benefit after RT alone or combination therapy was confined to patients with lower risk endometrioid adenocarcinomas (P<0.05). Conclusions: Adjuvant treatment for advanced stage endometrial cancer remains controversial. Our data suggests that a subgroup of patients may benefit from more aggressive treatment with combination chemotherapy and RT. Stratification by traditional prognostic factors did not identify a subgroup at lower risk for recurrence/progression. No significant financial relationships to disclose.

Upstaging based solely on positive peritoneal washing does not affect outcome in endometrial cancer

Surgical staging of endometrial carcinoma includes the collection of peritoneal washings in the abdomen and pelvis. A positive finding upstages patients to International Federation of Gynecology and Obstetrics stage IIIA. However, the prognostic significance of such an upstaging, and thus the justification for the routine performance of this procedure, is unclear. This 5-year retrospective study was conducted to determine the frequency and prognostic significance of upstaging of endometrial carcinoma based solely on positive washings. The cohort for the study was collected by review of pathology reports of all washings that were performed prior to hysterectomies for suspected endometrial carcinomas over a 5-year period (01/1995–12/1999). Cases with positive cytology were selected if there was no grossly apparent intraperitoneal disease, no histologic evidence of extra-uterine tumor and the cases would otherwise have been considered stage I or II (case group). An age-matched control group was selected of stage I and II patients with the same histologic subtypes and negative washings (n=19). Of 220 endometrial carcinomas, peritoneal washing cytology was abnormal in 19 (8.6%) and was solely responsible for upstaging only 10 patients (4.5% of all cases, eight—endometrioid, one–serous, one–mixed; nine stage IA or IB and one stage IIB). Adjuvant therapy was administered in 90% of the case group and 74% of the control group. After a median follow-up of 51 months (case group) and 63 months (control group), we found only a single patient with progression of disease (recurrence, metastases or death) in the control group. It is concluded that abnormal cytology without other evidence of extrauterine disease leads to upstaging of a minority of endometrial carcinoma patients (4.5%), but does not appear to affect their overall outcome. Although this is a small single site study, it raises questions about the value of this procedure in patients with endometrial cancer.

Surgical Staging for Patients Presenting With Grade 1 Endometrial Carcinoma

To examine the impact of surgical staging of patients presenting with grade 1 endometrial cancer. The charts of all patients who presented for surgery for endometrial cancer between March 1997 and July 2003 were analyzed for demographic data, final tumor histology, grade, stage, and complications. A total of 349 patients underwent surgical management for endometrial cancer. Preoperatively, 181 (52%) were identified with grade 1 disease, with a mean age of 61 years (range 27-89). Surgical staging (pelvic +/- para-aortic lymphadenectomy) was performed in 82% of cases and was omitted only in cases when disease was apparently confined to the endometrium and surgical risk was high. In staged patients, 3.2% had severe surgical complications. There were 2 perioperative mortalities (1 pulmonary emboli and 1 myocardial infarct). In comparison of pre- and postoperative histology, 19% of patients were upgraded, with 15% grade 2, 0.5% grade 3, 2.5% serous or clear cell, and 1% mixed mesodermal tumor. Lymph node metastases were found in 3.9% of patients presenting with grade 1 endometrial cancer, and 10.5% had extrauterine spread (> IIb). High-risk uterine features, including myometrial invasion more than 1/2, grade 3 lesions, high-risk histologic variants, and/or cervical involvement, were found in 26% of the patients. No patients with stage Ia-IIb endometrioid cancer received adjuvant teletherapy or chemotherapy. Four patients with low-risk uterine features were found to have extrauterine disease. Twelve percent of patients received adjuvant therapy, and 17% avoided teletherapy and/or chemotherapy based on surgical staging. Surgical staging in patients presenting with grade 1 endometrial cancer significantly impacted postoperative treatment decisions in 29% of patients. Omitting lymphadenectomy in patients presenting with grade 1 endometrial cancer may lead to inappropriate postoperative management.

A Comparison of Stages IB1 and IB2 Cervical Cancers Treated With Radical Hysterectomy. Is Size the Real Difference?

To compare stages IB1 and IB2 cervical cancer, the authors conducted a review of all patients with stage IB cancer of the cervix who underwent a type III radical hysterectomy with bilateral pelvic lymphadenectomy at theirinstitutions between 1990 and 2000. They identified 195 patients who had no gross extrauterine disease and sufficient data for analysis. One hundred seventy-seven (91%) subjects also underwent a bilateral paraaortic lymphadenectomy. No patient received preoperative radiation therapy. The mean age of the study subjects was 41.3 years. One hundred nine patients with tumor size 4 cm or less were identified as stage IB 1 and 86 whose tumor was larger than 4 cm were considered stage IB2. Tumor characteristics included lymphovascular space involvement in 98 women (53%), parametrial involvement in 31 (15.9%), and outer two thirds cervical stromal involvement in 110 (58.2%). Histologic cell type was squamous in 144 (73.8%) patients, adenocarcinoma in 37 (19%), adenosquamous in 10 (5.1%), and a mixture of small and clear in 4 (2.1%). Tumor grade was identified in 189 patients, of whom 9 (4.7%) were grade 1, 92 (47.1%) were grade 2, and 88 (45.1%) were grade 3. Stage IB1 and IB2 patients had a similar cell type and grade distribution, but those with stage IB2 had a significantly greater number of high-risk factors. Lymphovascular space involvement, outer two thirds cervical invasion, parametrial involvement, and nodal involvement were all more common in these women. There were no significant differences seen in rates of perioperative or postoperative complications, except that more patients with stage IB2 disease who received adjuvant radiation therapy were more likely to develop a postoperative bowel obstruction. Univariate analysis found no factors that were significant predictors of surgical complications. Positive pelvic nodes were seen in 38 (19.5%) patients, of whom 14 (12.8%) were stage IB1 and 24 (27.9%) were stage IB2. Two women with stage IB1 and 7 with stage IB2 disease had parametrial involvement. Univariate analysis of clinicopathologic factors identified lymphovascular space invasion (P = 0.001), >2/3 depth of invasion (P = 0.011), parametrial involvement (P = 0.001), disease stage (P = 0.008), and age of patient (P = 0.048) to be significant predictors of nodal involvement. After multivariate analysis, lymphovascular space involvement and parametrial involvement emerged as highly significant predictors of nodal involvement (odds ratios, 6.4; CI = 2.4-1.7 and 8, CI = 3.1-20, respectively). Median follow up in this series was 35 months. In that time, 10 patients with stage IB1 and 20 with stage IB2 tumors had disease recurrence. The overall disease-free survival was 92.5% for stage IB1 patients and 74.3% for stage IB2 patients (P = 0.009 for difference). Univariate analysis found that nodal positivity, lymphovascular space involvement, parametrial involvement, and outer two thirds stromal involvement were all significantly associated with disease-free survival, regardless of disease stage. After univariate analysis, lymphovascular involvement and outer two thirds stromal involvement were identified as independent predictors of disease-free survival. The relative risks were 7.75 (CI = 2-27; P = 0.0001) and 5.8 (CI = 2-20; P = 0.0029), respectively.

Lymphadenectomy in Apparent Early-Stage Endometrial Carcinoma: Do Numbers Count?

Endometrial carcinoma is the most common gynecologic malignancy in Western countries, with an overall annual incidence in the United States of 25 per 100,000, increasing to more than 85 per 100,000 in women 60 years or older. Because the majority of patients present with early-stagedisease,theprognosisofendometrialcarcinoma patients is generally good, with 5-year overall and cancerspecific survival rates of 80% to 85% and 90% to 95%. 1-4 Endometrial carcinoma is primarily a cancer of postmenopausalwomen,withconcurrentmorbiditiessuchasobesity, hypertension, and diabetes. Given the favorable outcome for the majority of cases, the challenge is to effectively select those patients at increased risk of relapse who might benefit from more extensive surgical procedures and adjuvant therapies, and to avoid overtreatment of low-risk cases that would be exposed unnecessarily to the risk of excess morbidity. Since the Gynecologic Oncology Group (GOG)-33 staging study, 5,6 which reported an overall 9% risk of pelvic lymph node metastases in clinical stage I endometrial cancer (25% for cases with outer-third myometrial invasion and 18% for grade 3 disease), gynecologic oncologists have advocated standard lymphadenectomy or sampling proceduresforallintermediate-andlow-riskendometrialcancer patients. It should be noted that GOG-33 included 12% patients, who at laparotomy were found to have macroscopic extrauterine disease; of these, 51% had pelvic metastases, and 23% had aortic node metastases. Among the patients without gross intraperitoneal spread, only 7% and 4% had positive pelvic or aortic nodes, respectively. Women at high risk ( 10%) for pelvic node metastasis were those with grade 3 and outer-third invasion, while all other cases had low to moderate ( 5% to 10%) risk. 6 This is in accordance with the COSA-NZ-UK trial, 7 which re

Diagnosis of endometrial cancer by hysteroscopy does not increase the risk for microscopic extrauterine spread in early-stage disease

The purpose of this study was to determine whether women with endometrial cancer have a higher incidence of microscopic extrauterine spread in early-stage disease when diagnosed by hysteroscopy compared with being diagnosed by dilatation and curettage (D&C) or endometrial biopsy (Pipelle). We retrospectively reviewed the medical records of 110 patients who had undergone surgical staging for endometrial cancer from January 1997 to December 2003. They all had a preoperative histological diagnosis of endometrial carcinoma without evidence of extrauterine disease. Diagnosis was made by hysteroscopy in 64 patients (58.2%), by D&C in 17 (15.5%), and by endometrial biopsy using a Pipelle device in 29 (26.3%). The groups were compared for known prognostic factors for microscopic extrauterine spread, including age, grade, stage, and vascular space involvement, and did not differ in these parameters. Microscopic intraperitoneal disease and positive peritoneal cytology were considered the primary endpoints of this analysis. Peritoneal cytology was positive in three of 110 (2.7%) patients. The presence of positive peritoneal cytology was not associated with hysteroscopy as the diagnostic procedure. We conclude that diagnosis of endometrial cancer by hysteroscopy does not increase the risk of microscopic intraperitoneal spread compared with diagnosis by D&C or endometrial biopsy (Pipelle).

Endometrial cancer: the management of high-risk disease.

Patients with endometrial cancer have an overall good prognosis. Patients with tumors invading deep into the myometrium or the cervical stroma or with extrauterine spread and patients with uterine papillary serous carcinoma (UPSC) or clear cell carcinoma (CCC) are at increased risk of relapse and represent a therapeutic challenge. Surgical treatment remains the cornerstone of therapy. Hysterectomy with bilateral salpingo-oophorectomy, washings, and careful assessment for intra-abdominal tumor should be performed with pelvic and para-aortic lymph node dissection when indicated based on grade of tumor and depth of invasion. All patients with UPSC or CCC should have pelvic and para-aortic lymph node dissection and omentectomy performed. Gross extrauterine disease should be resected. Radiotherapy has been the traditional adjuvant treatment for all high-risk patients. For patients with advanced disease (stage III-IV) combination chemotherapy with cisplatin and doxorubicin has been found to be superior to radiotherapy. For patients with advanced disease, treatment with a three-drug combination of cisplatin, doxorubicin, and paclitaxel has been shown to increase survival. It remains to be seen whether adjuvant chemotherapy in patients with high-risk disease in a lower stage will improve survival and possibly replace adjuvant radiotherapy in some patient groups.

A need for laparoscopic evaluation of patients with endometrial carcinoma selected for conservative treatment

Background The aim of this paper was to report two cases of extrauterine disease in patients with early stage endometrial cancer (EC) who desired fertility-sparing management. Cases Two patients presenting an apparent early stage EC and desiring conservative management. The two patients, aged 35 and 36 years old, had a grade 1 and grade 2 EC diagnosed after curettage or hysteroscopic resection of a polyp. Ultrasound (US) imaging was normal (ovary). Once informed about the risk of recurrence, both patients opted for conventional therapy (hysterectomy with bilateral salpingo-oophorectomy). A small ovarian carcinoma was found in one patient and isolated positive peritoneal cytology in the other. Conclusions These cases seem to suggest that laparoscopic evaluation including adnexal exploration and peritoneal cytology (and possibly pelvic lymphadenectomy) should be performed in patients with early stage EC selected for conservative management to confirm the absence of extrauterine disease.

Prognosis of papillary serous, clear cell, and grade 3 stage I carcinoma of the endometrium

Objective The purpose of this study was to evaluate patients with uterine papillary serous carcinoma (UPSC), clear cell (CC), and grade 3 endometrioid (G3) surgically stage I endometrial cancer. Methods The 25th Annual Report (AR) of FIGO was used to identify patients with endometrial cancers who were surgically staged. For comparison, all cancers reported were evaluated with particular interest in patients with stage I UPSC, CC, and G3. Incidence, substage, post-surgical treatment, and survival were identified. Results Of 5694 endometrial cancer patients reported to the AR, 3996 (70%) were surgically stage I. There were 148 UPSC, 59 CC, and 325 with G3 lesions. UPSC and CC represent 5.2% of all stage I cancers while 8.1% are G3. Although there were greater number of UPSC, CC, and G3 with extrauterine disease, about 50% of UPSC and CC were stage I. This compares to 81% for G1, 68% for G2, and only 42% for G3. There were more IA cancers with UPSC and CC than G3 (22%, 33%, and 17%, respectively). Survival (5 years) for UPSC and CC was 72% and 81%, respectively, compared to 76% for G3 lesions. Postoperative radiation improved survival somewhat (6–8%) but the difference was not significant. Conclusion UPSC and CC histotypes when diagnosed as stage I have a better survival than commonly perceived and equal to G3 endometrioid cancers. Postoperative radiation improves survival but not significantly so. The role of chemotherapy has not been defined.

Morbid obesity and endometrial cancer: surgical, clinical, and pathologic outcomes in surgically managed patients

Objective To evaluate surgical, clinical, and pathologic outcomes of patients with endometrial cancer managed with primary surgery when stratified by body mass index (BMI). Methods A review of 356 consecutive patients undergoing primary surgical management of endometrial carcinoma by a single gynecologic oncology service from 1997 to 2003 was undertaken. Patients were divided into three groups based on preoperative BMI. Data regarding surgical and pathologic outcomes were compared. Results Twenty-two percent of patients had a BMI >40, 38% were 30–40, and 40% were <30. Overall, 90% underwent some surgical staging, including 93%, 92%, and 81% of those with a BMI <30, 30–40, and >40, respectively. In fully staged patients, a median 23 lymph nodes were removed in all groups, without a significant difference in the number of aortic nodes recovered between the heaviest and lightest groups. Aortic lymphadenectomy was performed in 48% patients with BMI >40 compared with 74% of patients with BMI <30. Intraoperative and postoperative complications were rare and similar between groups. Patients with BMI >40 were more commonly diagnosed with grade 1 tumor than patients with BMI <30. Rates of nodal metastasis were similar between groups and occurred in 11% of patients overall. In those with a BMI >40, extrauterine disease was encountered in 12% of patients. Conclusions While surgical staging of morbidly obese patients is difficult, adequate lymphadenectomy can be performed safely; although aortic nodes are less commonly resected in this population. Staging remains important in obese women, as the risk of extrauterine disease, including lymph node metastasis, is similar to that in women with ideal body weight.

High-dose rate brachytherapy for Stage I/II papillary serous or clear cell endometrial cancer

Objective. To determine the efficacy of high-dose rate brachytherapy as adjuvant treatment for Stage I/II papillary serous or clear cell endometrial cancer. Methods. A retrospective study of all patients with Stage I/II papillary serous or clear cell endometrial cancer treated with high-dose rate brachytherapy between 1995 and 2001 was performed. Following surgical staging, which included hysterectomy with pelvic and aortic lymphadenectomy, all patients without extrauterine disease were treated with high-dose rate brachytherapy and followed for recurrence. The locations of recurrences were noted and were classified as local or distant. Results. Three (13%) recurrences occurred among 24 patients with Stage I/II papillary serous or clear cell carcinoma. The risk of recurrence was similar for papillary serous and clear cell cancer (12% vs. 12%). Local control was achieved in 96%. The risk of recurrence for those with no myometrial invasion, less than 1/2, or more than 1/2 myometrial invasion was 0%, 10%, and 50%, respectively ( P < 0.04). Two of the three recurrences were distant and all patients with recurrence died despite additional treatment. Conclusions. High-dose rate brachytherapy (HDR) as the sole adjuvant treatment of Stage I/II papillary serous or clear cell carcinoma is associated with a 13% risk of recurrence. Although local control with HDR is excellent, the risk of distant recurrence is increased with deep myometrial invasion. High-dose rate brachytherapy is adequate for Stage IA cases, but more aggressive treatment combining chemotherapy with HDR should be evaluated for more advanced Stage I/II cases.

Location of the appendix in the gravid patient: A re-evaluation of the established concept

Hodjati H, Kazerooni T(Shiraz University of Medical Sciences, Shiraz, Iran)BackgroundAppendicitis is the most common extrauterine disease that requires surgery during pregnancy. Appendicitis is associated with premature labor pains and spontaneous abortion. Many years ago, it was reported that pregnancy displaces the appendix upward. The position of the appendix during pregnancy was re-evaluated.Study designThis study group consisted of 165 pregnant women who had a cesarean section, 26 pregnant women with acute appendicitis, and 100 women with acute appendicitis who were not pregnant. The location of the base of the appendix was considered to have changed if it was at least 2 cm from McBurney's point.FindingsIn the cesarean section group, 15% had a position change for the appendix; in the pregnancy plus appendicitis group, 23% had a position change; and in the control group, 17% had a position change. These differences were not significant.ConclusionsThe findings of this study do not support changes in the position of the appendix in the majority of women with pregnancy. A high level of suspicion should be maintained in pregnant women with right lower quadrant pain. Larger studies should be conducted to define the position of the appendix during pregnancy.CommentA more complete description of the investigators' methodology would have strengthened this article considerably. The authors leave the reader to guess the following: Who evaluated the location of the appendix tip? What was their training? Were there multiple evaluators/observers? If so, what was the agreement between observers as to the location of the appendix tip? Even with these omissions, I found this study fun because it attempts to dispel a medical myth: that the uterus always displaces the appendix into the right upper quadrant as pregnancy progresses so that appendicitis in pregnant women presents as right upper quadrant pain. Hodjati and Kazerooni demonstrate that displacement of the appendix into the right upper quadrant is not the rule and that even minimal displacement of the appendix from McBurney's point occurs in a minority of pregnant women.The take-home message is that a high level of clinical suspicion is needed to quickly and correctly diagnose appendicitis in pregnant women. Put it back on the differential diagnosis list for right lower quadrant pain. Hodjati H, Kazerooni T (Shiraz University of Medical Sciences, Shiraz, Iran) BackgroundAppendicitis is the most common extrauterine disease that requires surgery during pregnancy. Appendicitis is associated with premature labor pains and spontaneous abortion. Many years ago, it was reported that pregnancy displaces the appendix upward. The position of the appendix during pregnancy was re-evaluated. Appendicitis is the most common extrauterine disease that requires surgery during pregnancy. Appendicitis is associated with premature labor pains and spontaneous abortion. Many years ago, it was reported that pregnancy displaces the appendix upward. The position of the appendix during pregnancy was re-evaluated. Study designThis study group consisted of 165 pregnant women who had a cesarean section, 26 pregnant women with acute appendicitis, and 100 women with acute appendicitis who were not pregnant. The location of the base of the appendix was considered to have changed if it was at least 2 cm from McBurney's point. This study group consisted of 165 pregnant women who had a cesarean section, 26 pregnant women with acute appendicitis, and 100 women with acute appendicitis who were not pregnant. The location of the base of the appendix was considered to have changed if it was at least 2 cm from McBurney's point. FindingsIn the cesarean section group, 15% had a position change for the appendix; in the pregnancy plus appendicitis group, 23% had a position change; and in the control group, 17% had a position change. These differences were not significant. In the cesarean section group, 15% had a position change for the appendix; in the pregnancy plus appendicitis group, 23% had a position change; and in the control group, 17% had a position change. These differences were not significant. ConclusionsThe findings of this study do not support changes in the position of the appendix in the majority of women with pregnancy. A high level of suspicion should be maintained in pregnant women with right lower quadrant pain. Larger studies should be conducted to define the position of the appendix during pregnancy. The findings of this study do not support changes in the position of the appendix in the majority of women with pregnancy. A high level of suspicion should be maintained in pregnant women with right lower quadrant pain. Larger studies should be conducted to define the position of the appendix during pregnancy.

Preliminary analysis of RTOG 9708: adjuvant postoperative radiotherapy combined with cisplatin/paclitaxel chemotherapy after surgery for patients with high-risk endometrial cancer

Purpose Patients with completely resected high-risk endometrial cancer have a risk of disease recurrence even with the addition of adjuvant pelvic radiotherapy (RT). A Phase II study was completed by the Radiation Therapy Oncology Group to assess the safety and toxicity of chemotherapy when combined with pelvic RT for these patients. Methods and materials Eligibility requirements included a total abdominal hysterectomy and bilateral salpingo-oophorectomy with Grade 2 or 3 endometrial adenocarcinoma with >50% myometrial invasion, stromal invasion of the cervix, or pelvic-confined extrauterine disease. This study was designed to administer 4500 cGy in 25 fractions to the pelvis, along with cisplatin (50 mg/m 2) on Days 1 and 28. Vaginal brachytherapy with a low-dose-rate applicator (1 × 20 Gy to the surface) or high-dose-rate applicator (3 × 6 Gy to the surface) was performed after external beam RT. Four courses of cisplatin (50 mg/m 2) and paclitaxel (175 mg/m 2) were given at 4-week intervals after RT completion. Results Forty-six patients were entered between October 1997 and April 1999. Two patients were ineligible (one with previous bladder cancer and one who had undergone surgery >8 weeks before the start of RT). Follow-up ranged from 6.9 to 48.8 months (median, 28.7 months). The disease was Stage III, II, and I in 66%, 16%, and 18% of patients, respectively. Two patients were not assessable because of incomplete treatment data. The protocol completion rate was 98% (41 of 42 assessable patients). Acute toxicity during RT/chemotherapy was Grade 1 in 27%, Grade 2 in 43%, Grade 3 in 27%, and Grade 4 in 2%. During adjuvant chemotherapy, the toxicity was Grade 1 in 7%, Grade 2 in 7%, Grade 3 in 21%, and Grade 4 in 62%. Severe toxicity was primarily hematologic. Chronic toxicity was Grade 1 in 20%, Grade 2 in 39%, Grade 3 in 16%, and Grade 4 in 2%, including 1 patient with a Grade 4 small bowel complication. At 24 months, the pelvic recurrence, regional recurrence, distant recurrence, disease-free survival, and overall survival rate was 2%, 3%, 17%, 83%, and 90%, respectively. Conclusion This treatment protocol demonstrated an excellent treatment completion rate and expected toxicity. Longer follow-up is needed to assess the outcome. To assess the efficacy of this adjuvant treatment program, a Phase III trial (Radiation Therapy Oncology Group 9905) was designed with high-risk uterine-confined disease to be randomized between pelvic RT alone and pelvic RT with chemotherapy.

Primary primitive neuroectodermal tumor of the uterus: a report of two cases and review of the literature

Background. Primary primitive neuroectodermal (pPNET) tumors rarely occur in adults, and they very rarely present as primary tumors of the uterus. Only 12 reported cases of pPNET of the uterus have been published in the English literature. We report two additional cases treated at the Roswell Park Cancer Institute, Buffalo, NY, between 1999 and 2002. Cases. Two postmenopausal patients presenting with abnormal uterine bleeding underwent endometrial biopsy, and subsequently staging laparotomy. The diagnosis of pPNET in both cases was confirmed only by extensive immunohistochemical analysis of the tumors. One patient with disease confined to an endometrial polyp received no adjuvant therapy, while the second patient with extrauterine disease received adjuvant pelvic radiation followed by chemotherapy. Conclusions. The diagnosis of pPNET of the uterus may be a challenge. Features of diagnostic significance include positive staining with neuron-specific enolase, presence of neurosecretory granules, and positive staining with the MIC-2 gene. Currently, there is no uniformity in the treatment of these cases since the majority of the patients reported to date have had surgery, chemotherapy, and/or radiation therapy.