François Golfier

Guidelines for the management of ovarian cancer during pregnancy

Adnexal masses may be detected during prenatal ultrasound, and ovarian cancer may be suspected during pregnancy. Even though such masses are rarely malignant (1/10,000 to 1/50,000 pregnancies), the possibility of borderline tumour or cancer must be considered. It is a common assumption by both patients and physicians that if an ovarian cancer is diagnosed during pregnancy, treatment necessitates sacrificing the well-being of the fetus. However, in most cases, it is possible to offer appropriate treatment to the mother without placing the fetus at serious risk. The care of a pregnant woman with cancer involves evaluation of sometimes competing maternal and fetal risks and benefits. These recommendations attempt to balance these risks and benefits; however, they should be considered advisory and should not replace specific interdisciplinary consultation with specialists in maternal-fetal medicine, gynecologic oncology and pediatrics, as well as imaging and pathology, as needed. Second level ultrasound including Doppler is needed. MRI is not often necessary, and CA 125 is of low contribution. We suggest surgery be performed after 15 weeks gestation for ovarian masses which (1) persist into the second trimester, (2) are greater than 5-10 cm in diameter, or (3) have solid or mixed solid and cystic ultrasound characteristics. During the antepartum period surgical staging and debulking, unilateral salpingo-oophorectomy on the side with the tumour, peritoneal cytology and exploration are necessary. Women found to have advanced stage epithelial ovarian cancer should consider having completion of the debulking of the reproductive organs at the conclusion of the pregnancy. If chemotherapy is indicated, we recommend delaying administration, if possible, until after the delivery or at least after 20 weeks in order to minimize the potential fetal toxicity.

Sentinel node biopsy for the management of early stage endometrial cancer: Long-term results of the SENTI-ENDO study

OBJECTIVE We report the long-term results of the SENTI-ENDO study evaluating the impact of sentinel lymph node (SLN) biopsy on management and survival in patients with early stages of endometrial cancer (EC). METHODS Patients with FIGO stage I-II EC underwent pelvic SLN biopsy after cervical dual injection (technetium and patent blue) and systematic pelvic node dissection. This study is a secondary endpoint reporting the long-term recurrence free survival (RFS) and the impact of the SLN procedure on adjuvant therapies. RESULTS The median follow-up was 50 months (range: 3-77 months). Eighteen of the 125 patients (14.4%) experienced a recurrence. The 50-month recurrence-free survival (RFS) was 84.7% with no difference between patients with and without detected SLN (p = 0.09). Among patients with detected SLN (111), no difference in RFS was observed between those with and without positive SLN (p = 0.5). In the whole population, adjuvant therapy was performed in low-, intermediate- and high-risk groups in 31 of 64 patients (48.4%), 28 of 37 patients (75.7%) and 14 of 17 patients (82.3%), respectively (p = 0.0001). For the 111 patients with detected SLN, EBRT was performed in 27 of the 89 with negative SLN and in 11 of the 14 with positive SLN (p = 0.001). Chemotherapy was performed more frequently in patients with positive SLN (6/12, 50%) than in patients with negative SLN (7/56, 12.5%) (p = 0.009). CONCLUSIONS Our results support the impact of SLN biopsy on surgical management and indications for adjuvant therapies. Further studies are required to assess the clinical impact of the SLN biopsy in early stage EC.

Bowel Endometriosis: Preoperative Diagnostic Accuracy of 3.0-T MR Enterography—Initial Results

PURPOSE To prospectively determine the accuracy of 3.0-T magnetic resonance (MR) enterography in the preoperative assessment of deep infiltrating endometriosis (DIE) lesions located in the bowel above the rectosigmoid junction. MATERIALS AND METHODS Institutional review board approval for this study was obtained, and each patient gave written informed consent. Over 18 months, patients with known pelvic DIE who were scheduled for surgery were recruited. Consecutive patients suspected of having bowel endometriosis above the rectosigmoid junction underwent 3.0-T MR enterography. Two blinded readers independently performed a systematic analysis of nine bowel segments above the rectosigmoid junction. MR images were compared with surgical and pathologic findings. Efficacy parameters were calculated with 95% confidence intervals (CIs). Interobserver agreement was assessed with κ statistics. RESULTS Among the 43 patients enrolled in this study, 33 underwent surgery and were included in the final analyses. Sixteen (48%) patients had bowel DIE lesions located above the rectosigmoid junction at surgery and histopathologic examination. Twenty-six lesions were analyzed, including four ileal, two ileocecal, three cecal, three appendicular, and 14 sigmoid colon lesions. For the diagnosis of these lesions, MR imaging showed sensitivities of 92% (95% confidence interval [CI]: 81.7, 100) for reader 1 and 96% (95% CI: 87.1, 100) for reader 2 and specificities of 100% (95% CI: 98.8, 100) for both readers. The κ value was 0.97. CONCLUSION These results show 3.0-T MR enterography is accurate in the preoperative diagnosis and mapping of bowel DIE lesions located above the rectosigmoid junction. Online supplemental material is available for this article.

Transvaginal cervicoisthmic cerclage as an alternative to the transabdominal technique.

OBJECTIVES To analyse the foetal outcome after transvaginal cervicoisthmic cerclage, to determine whether it is a valid alternative to the reference transabdominal technique. STUDY DESIGN Description of the vaginal operative technique, retrospective review of 20 cervicoisthmic cerclage patients from 1990 to 2000. RESULTS In the curative group of women with a history of late pregnancy losses or premature deliveries and usually previous failed classical cervical cerclage, the foetal survival rate improved from 18% before cerclage to 79% after cerclage. No operative complications were reported. In the prophylactic group, typically characterised by the absence of the cervix as a consequence of surgery for invasive cervical cancers, the foetal survival rate was 83% after cerclage. CONCLUSIONS The transvaginal cervicoisthmic cerclage allows a high foetal survival rate without complications in highly selected patients with poor obstetrical history. Because of its simplicity, this technique should replace the transabdominal route for surgeons experienced in vaginal surgery.

Reappraisal of in utero Stem Cell Transplantation Based on Long-Term Results

The therapeutic field of in utero transplantation of stem cells, into human fetuses, has developed since 1988 with the hope of improved probability of engraftment and tolerance, due to immune immaturity of the host. Fifteen years later, it is possible to evaluate the results that we and others have obtained in the treatment of several fetal diseases. Seven fetal patients have been treated in Lyon: In 2 cases, pregnancy termination was induced by the in utero injection; in the 5 other cases, engraftment was obtained and repeatedly documented with presence of donor HLA antigens and/or Y chromosome in recipients. In the 2 patients with combined immunodeficiency disease, a sustained reconstitution of immunity was obtained as a result of the transplant but other complications occurred thereafter. In patients with thalassemia major, Niemann-Pick disease or hemophilia, a very partial and very transitory benefit was only obtained. Approximately 33 other patients with immunodeficiencies, hemoglobinopathies or inborn errors of metabolism have been treated worldwide, over the last 13 years, with a comparable method, using parental or fetal stem cells transplanted in utero. Successful treatment has usually been recorded in immunodeficiencies, and insufficient results have been obtained in the other cases. This form of treatment can therefore be recommended after prenatal diagnosis of combined immunodeficiency but additional research is required to improve the degree of engraftment, the lack of resistance of the host and the ‘space’ available for hematopoiesis in the other conditions.

Keeping Data Continuous when Analyzing the Prognostic Impact of a Tumor Marker: An Example with Cathepsin D in Breast Cancer

The prognostic value of cathepsin D has been recently recognized, but as many quantitative tumor markers, its clinical use remains unclear partly because of methodological issues in defining cut-off values. Guidelines have been proposed for analyzing quantitative prognostic factors, underlining the need for keeping data continuous, instead of categorizing them. Flexible approaches, parametric and non-parametric, have been proposed in order to improve the knowledge of the functional form relating a continuous factor to the risk. We studied the prognostic value of cathepsin D in a retrospective hospital cohort of 771 patients with breast cancer, and focused our overall survival analysis, based on the Cox regression, on two flexible approaches: smoothing splines and fractional polynomials. We also determined a cut-off value from the maximum likelihood estimate of a threshold model. These different approaches complemented each other for (1) identifying the functional form relating cathepsin D to the risk, and obtaining a cut-off value and (2) optimizing the adjustment for complex covariate like age at diagnosis in the final multivariate Cox model. We found a significant increase in the death rate, reaching 70% with a doubling of the level of cathepsin D, after the threshold of 37.5 pmol mg−1. The proper prognostic impact of this marker could be confirmed and a methodology providing appropriate ways to use markers in clinical practice was proposed.

Methotrexate for 2000 FIGO low-risk gestational trophoblastic neoplasia patients: efficacy and toxicity

OBJECTIVE We sought to review efficacy and toxicity of an 8-day methotrexate (MTX) regimen in the treatment of patients with low-risk gestational trophoblastic neoplasia (GTN) from the French Trophoblastic Disease Reference Center. STUDY DESIGN Between 1999 and 2006, 142 low-risk GTNs were diagnosed according to International Federation of Gynecology and Obstetrics (FIGO) criteria for GTN and to the FIGO scoring system. We report their characteristics, remission/resistance/recurrence rates, and treatment toxicity. RESULTS The 8-day MTX regimen achieved a 77.5% remission rate. All patients but 1 (99.9%) achieved remission and remained disease free until the time of analysis. Severe (grade 3 or 4) blood/bone marrow toxicity and metabolic/laboratory toxicity was noted in 4.2% of cases, of which 2 (1.4%) were grade 4. CONCLUSION For patients with GTN diagnosed according to FIGO criteria and considered low risk according to the FIGO scoring system, an 8-day MTX regimen is an adequate treatment associating a high rate of remission to a low rate of toxicity.

Contribution of referent pathologists to the quality of trophoblastic diseases diagnosis

OBJECTIVE To evaluate the contribution of referent pathologists (RPs) to the quality of diagnosis of trophoblastic diseases and to study the level of diagnostic agreement between the initial pathologists and the RPs. METHODS This observational retrospective study was carried between 1 November 1999 and 11 January 2011 using the database of the French Trophoblastic Disease Reference Centre in Lyon. All files for hydatiform moles (HMs), trophoblastic tumours and non-molar pregnancies for which there was an initial suspicion of trophoblastic disease were included, whenever there was rereading of the slides by an RP. A total of 1851 HMs and 150 gestational trophoblastic tumours were analysed. RESULTS When the initial pathologist diagnosed a complete mole, the RP confirmed the diagnosis in 96% of cases. When the initial pathologist diagnosed a partial mole, the RP confirmed the diagnosis in only 64% of cases. For trophoblastic tumours, when the initial pathologist diagnosed a choriocarcinoma, the RP confirmed the diagnosis in 86% of cases. When the initial anatomopathology suggested an invasive mole, the diagnosis was confirmed in 96% of cases. Finally, when the initial diagnosis was a placental site trophoblastic tumour or an epithelioid trophoblastic tumour, the RP confirmed the diagnosis in 60 and 100% of cases, respectively. CONCLUSION A systematic policy of rereading of slides for all suspicious moles improves the quality of management of trophoblastic diseases at a national level.

Placental site and epithelioid trophoblastic tumours: Diagnostic pitfalls

OBJECTIVE To describe the clinical and histological pitfalls in the diagnosis of placental site trophoblastic tumours (PSTT) and epithelioid trophoblastic tumours (ETT), two rare types of gestational trophoblastic neoplasia (GTN). METHODS This retrospective, observational, study was carried out in the French Trophoblastic Disease Reference Centre, Lyon, between 2000 and 2011. Due to the many similarities in the diagnosis, treatment and prognosis of PSTT and ETT, these two types of tumour were investigated together. Twenty-two patients with PSTT or ETT were analysed. RESULTS The clinical presentation of these two types of tumour was irregular vaginal bleeding (55%) or amenorrhoea (27%), with a median plasma hCG level of 205IU/L. Seven of the 22 patients (32%) were initially misdiagnosed as an ectopic pregnancy. Median age at presentation was 35-years, with a median interval of 12months between the antecedent pregnancy and diagnosis of PSTT or ETT. The initial histological diagnosis was incorrect in 7/18 (39%) patients; there was a major disagreement with the referral pathologist in five of these seven patients (28%). CONCLUSIONS PSTT and ETT are the most difficult types of GTN to diagnose clinically and histologically. An incorrect diagnosis can lead to significant therapeutic deviations from the recommended first-line treatment, namely hysterectomy. Clinical and histological expertise is essential to avoid the pitfalls in the diagnosis of PSTT and ETT.

Laparoscopic uterovaginal anastomosis in Mayer-Rokitansky-Küster-Hauser syndrome with functioning horn

OBJECTIVE To reestablish uterovaginal continuity using a total laparoscopic procedure in Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome with a functioning right horn. DESIGN Case report. SETTING University hospital of Hotel Dieu de Lyon. PATIENT(S) A 13-year-old woman with cyclic abdominal pain. We diagnosed MRKH syndrome with cyclic pain due to a hematometra in a functioning right horn associated to a right hematosalpinx and a nonfunctioning left horn. INTERVENTION(S) Reestablishing uterovaginal continuity with excision of the left rudimentary horn via a total laparoscopic procedure. MAIN OUTCOME MEASURE(S) Restoring regular menstruation. RESULT(S) After total laparoscopic uterovaginal anastomosis and excision of the left nonfunctioning horn, the patients menstruation resumed 3 months later, and regular, unimpeded menstrual flow was still present at the 2-year-follow-up evaluation. CONCLUSION(S) Total laparoscopic reestablishment of uterovaginal continuity in MRKH syndrome with a functioning horn is a valuable alternative to the currently recommended treatment (laparotomy and radical excision of the rudimentary uterus).