Eric Leblanc

Detection rate and diagnostic accuracy of sentinel-node biopsy in early stage endometrial cancer: a prospective multicentre study (SENTI-ENDO)

BACKGROUND Retrospective single-centre series have shown the feasibility of sentinel lymph-node (SLN) identification in endometrial cancer. We did a prospective, multicentre cohort study to assess the detection rate and diagnostic accuracy of the SLN procedure in predicting the pathological pelvic-node status in patients with early stage endometrial cancer. METHODS Patients with International Federation of Gynecology and Obstetrics (FIGO) stage I-II endometrial cancer had pelvic SLN assessment via cervical dual injection (with technetium and patent blue), and systematic pelvic-node dissection. All lymph nodes were histopathologically examined and SLNs were serial sectioned and examined by immunochemistry. The primary endpoint was estimation of the negative predictive value (NPV) of sentinel-node biopsy per hemipelvis. This is an ongoing study for which recruitment has ended. The study is registered with ClinicalTrials.gov, number NCT00987051. FINDINGS From July 5, 2007, to Aug 4, 2009, 133 patients were enrolled at nine centres in France. No complications occurred after injection of technetium colloid and no anaphylactic reactions were noted after patent blue injection. No surgical complications were reported during SLN biopsy, including procedures that involved conversion to open surgery. At least one SLN was detected in 111 of the 125 eligible patients. 19 of 111 (17%) had pelvic-lymph-node metastases. Five of 111 patients (5%) had an associated SLN in the para-aortic area. Considering the hemipelvis as the unit of analysis, NPV was 100% (95% CI 95-100) and sensitivity 100% (63-100). Considering the patient as the unit of analysis, three patients had false-negative results (two had metastatic nodes in the contralateral pelvic area and one in the para-aortic area), giving an NPV of 97% (95% CI 91-99) and sensitivity of 84% (62-95). All three of these patients had type 2 endometrial cancer. Immunohistochemistry and serial sectioning detected metastases undiagnosed by conventional histology in nine of 111 (8%) patients with detected SLNs, representing nine of the 19 patients (47%) with metastases. SLN biopsy upstaged 10% of patients with low-risk and 15% of those with intermediate-risk endometrial cancer. INTERPRETATION SLN biopsy with cervical dual labelling could be a trade-off between systematic lymphadenectomy and no dissection at all in patients with endometrial cancer of low or intermediate risk. Moreover, our study suggests that SLN biopsy could provide important data to tailor adjuvant therapy. FUNDING Direction Interrégionale de Recherche Clinique, Ile-de-France, Assistance Publique-Hôpitaux de Paris.

Bilateral Negative Sentinel Nodes Accurately Predict Absence of Lymph Node Metastasis in Early Cervical Cancer: Results of the SENTICOL Study

PURPOSE Sentinel lymph node (SLN) biopsy may be used to target lymph node metastases in patients with early cervical cancer. Whether SLN biopsy only is acceptable in the staging and surgical management of early cervical cancer remains unknown. This prospective multicenter study (SENTICOL [Ganglion Sentinelle dans le Cancer du Col]) assessed the sensitivity and negative predictive value (NPV) of SLN biopsy. PATIENTS AND METHODS Adults with cervical carcinoma who met the International Federation of Gynecology and Obstetrics criteria for stage IA1 with lymphovascular space invasion to stage IB1 underwent technetium 99 lymphoscintigraphy and Patent Blue injection followed by laparoscopic lymph node mapping, SLN removal, and lymph node dissection. Only surgeons trained in SLN biopsy in cervical carcinoma participated in the study. SLNs and nonsentinel lymph nodes underwent routine staining. Negative SLNs were subjected to ultrastaging. The reference method was pelvic and/or para-aortic lymphadenectomy with histologic examination of all nodes. RESULTS One hundred forty-five patients were enrolled, and 139 were included in a modified intention-to-diagnose analysis. Intraoperative radioisotope-blue dye mapping detected at least one SLN in 136 patients (97.8%; 95% CI, 93.8% to 99.6%), 23 of whom had true-positive results and two who had false-negative results, yielding 92.0% sensitivity (23 of 25; 95% CI, 74.0% to 99.0%) and 98.2% NPV (111 of 113; 95% CI, 74.0% to 99.0%) for node metastasis detection. No false-negative results were observed in the 104 patients (76.5%) in whom SLN were identified bilaterally. CONCLUSION Combined labeling for node mapping was associated with high rates of SLN detection and with high sensitivity and NPV for metastasis detection. However, SLN biopsy was fully reliable only when SLNs were detected bilaterally.

Nodal-staging surgery for locally advanced cervical cancer in the era of PET

Chemoradiation therapy is deemed the standard treatment by many North American and European teams for treatment of locally advanced cervical cancer. The prevalence of para-aortic nodal metastasis in these tumours is 10-25%. PET (with or without CT) is the most accurate imaging modality to assess extrapelvic disease in such tumours. The true-positive rate of PET is high, suggesting that surgical staging is not necessary if uptake takes place in the para-aortic region. Nevertheless, false-negative results (in the para-aortic region) have been recorded in 12% of patients, rising to 22% in those with uptake during PET of the pelvic nodes. In such situations, laparoscopic surgical para-aortic staging still has an important role for detection of patients with occult para-aortic spread misdiagnosed on PET or PET-CT, allowing optimisation of treatment (extension of radiation therapy fields to include the para-aortic area). Complications of the laparoscopic procedure were noted in 0-7% of patients. Survival of individuals (missed by PET) with para-aortic nodal metastasis of 5 mm or less (and managed by extended field chemoradiation therapy) seems to be similar to survival of those without para-aortic spread, suggesting a positive therapeutic effect of the addition of staging surgery. Nevertheless, the effect on survival of potential delay of chemoradiation owing to use of PET and staging surgery, and acute and late complications of surgery followed by chemoradiation therapy (particularly in case of extended field chemoradiation to para-aortic area), need to be studied.

Prospective Multicenter Study Evaluating the Survival of Patients With Locally Advanced Cervical Cancer Undergoing Laparoscopic Para-Aortic Lymphadenectomy Before Chemoradiotherapy in the Era of Positron Emission Tomography Imaging

PURPOSE The aim of this prospective study conducted in three French comprehensive cancer centers was to evaluate the therapeutic impact on survival of laparoscopic para-aortic (PA) staging surgery in locally advanced cervical cancer (LACC) before chemoradiotherapy. PATIENTS AND METHODS We conducted a prospective multicenter study of 237 patients treated from 2004 to 2011 for LACC with negative positron emission tomography (PET) imaging of the PA area and undergoing laparoscopic PA lymphadenectomy. Radiation fields were extended to the PA area when PA nodes were involved. Chemoradiotherapy modalities were homogeneous across institutions. Patients with a poor prognosis histologic subtype or peritoneal carcinosis were excluded. RESULTS Patients had clinical International Federation of Gynecology and Obstetrics stages IB2 (n = 79), IIA (n = 10), IIB (n = 121), III (n = 22), or IVA (n = 5). One hundred ninety-nine patients had squamous carcinoma, and 38 had adenocarcinoma/adenosquamous lesions. Twenty-nine patients (12%) had nodal involvement (false-negative PET-computed tomography [CT] results)-16 with a PA nodal metastasis measuring more than 5 mm and 13 with a nodal metastasis measuring ≤ 5 mm. Event-free survival rates at 3 years in patients without PA involvement or with PA metastasis measuring ≤ or more than 5 mm were 74% (SE, 4%), 69% (SE, 21%), and 17% (SE, 14%; P < .001). CONCLUSION To our knowledge, this is the largest series of patients reported undergoing such a strategy. We obtained the same survival rate for patients with PA nodal metastasis ≤ 5 mm and patients without PA lymph node involvement, suggesting that this strategy is highly efficient in such patients. Conversely, the survival of patients with PA nodal involvement greater than 5 mm remained poor, despite the absence of extrapelvic disease on PET-CT imaging in this subgroup.

Laparoscopic restaging of borderline ovarian tumours: results of 30 cases initially presumed as stage IA borderline ovarian tumours

Objectives To review our experience with the laparoscopic restaging procedure of presumed early stage borderline ovarian tumours.

Maximal cytoreduction in patients with FIGO stage IIIC to stage IV ovarian, fallopian, and peritoneal cancer in day-to-day practice: a Retrospective French Multicentric Study

Objectives To evaluate the outcome of maximal cytoreductive surgery in patients with stage IIIC to stage IV ovarian, tubal, and peritoneal cancer regarding overall survival (OS) and disease-free survival (DFS). Materials and Methods Five hundred twenty-seven patients with stage IIIC (peritoneal) and stage IV (pleural) ovarian, fallopian tube, and peritoneal carcinoma underwent surgery between January 2003 and December 2007 in 7 gynecologic oncology centers in France. Patients undergoing primary and interval debulking surgery were included, whichever the number of chemotherapy cycles. The extent of disease, type of surgical procedure, and amount of residual disease were recorded. A multivariate analysis of the outcome was performed, taking into account the stage, grade, and timing of surgery. Results Median DFS was 17.9 months, but median OS was not reached at the time of analysis. Complete cytoreductive surgery, without evident residual tumor at the end of the procedure, was obtained in 71% of all patients (primary surgery, 33%). After neoadjuvant therapy, the rate of complete debulking surgery was higher (74%) compared to primary cytoreductive surgery (65%). Twenty-three percent of patients needed “ultra radical surgery” to achieve this goal. The most significant predictive factor for DFS and OS was complete cytoreductive surgery compared to any amount, even minimal (1–10 mm), of residual disease. In the group of patients with complete cytoreductive surgery, the patients undergoing surgery before chemotherapy showed better DFS than those having first chemotherapy. Conclusion The findings confirm that complete cytoreduction is the criterion standard of surgery in the management of advanced ovarian, peritoneal, and fallopian tube cancer, whatever the timing of surgery. With experienced teams, surgery was completed, without evident residual tumor in 71% of the cases.

Diagnostic value of intraoperative examination of sentinel lymph node in early cervical cancer: a prospective, multicenter study.

OBJECTIVES Sentinel lymph node (SLN) biopsy is a surgical procedure proposed in early cervical cancer. This technique yields the potential interest to reduce the morbidity of complete lymphadenectomy, which could then be performed only in case of positive SLN. Intraoperative examination has a major per-operative role in predicting nodal involvement and preventing a second step procedure. The aim of this study was to assess the diagnostic value of intraoperative examination with frozen section (FS) or imprint cytology (IC) of SLNs in early cervical cancer. METHODS Prospective study in 7 centers (01/2005-06/2007) including patients with stage IA1 and lymphovascular space involvement to IB1 cervical cancer (squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma). SLNs were detected with a combined method (Tc99m+blue dye) and then removed laparoscopically. Intraoperative examination (FS or IC) was not systematically performed but recommended in case of macroscopical nodal enlargement in 5 centers. Results of intraoperative examination were compared with final histology performed by Hematoxylin-Eosin-Safran staining and immunohistochemistry. The diagnostic value of intraoperative examination was calculated. RESULTS One hundred and thirty-nine patients were analyzed in the study. The combined detection rate was 97.8% per patient, with 454 detected SLNs. One hundred and two patients (73.4%) had an intraoperative examination (97 patients with FS and 5 with IC). Among patients with intraoperative examination, 5 SLNs were positive (all with macrometastasis at final histology), as compared with 22 metastatic nodes at final result. The 17 false negative SLNs were: 4 macrometastasis, 4 micrometastasis and 9 isolated tumor cells. Sensitivity of the intraoperative examination per node was 20.7% [95%CI: 7.8%-45.4%] and the negative predictive value 93.0% [95%CI: 89.0%-95.9%]. CONCLUSIONS Intraoperative examination of SLNs by FS and IC has a poor diagnostic value. This is mainly related to micrometastasis and isolated tumor cells, which are not detected by intraoperative techniques. Other techniques, like new molecular assays, should be investigated to improve intraoperative assessment of SLNs.

Surgical staging of early invasive epithelial ovarian tumors.

Early stage epithelial ovarian carcinoma is defined pathologically as a tumor strictly limited to one or both ovaries without any extra-ovarian disease (i.e., Stage IA or B of the International Federation of Gynecology and Obstetrics (FIGO) classification). This diagnosis can be obtained only after an exhaustive surgical staging procedure, performed as soon as the diagnosis of epithelial invasive ovarian carcinoma is established. This staging surgery currently encompasses a peritoneal cytology, the thorough inspection of all the visceral and parietal peritoneal surfaces with biopsy of any abnormality, total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH + BSO), random peritoneal biopsies, omentectomy, appendectomy and bilateral pelvic and para-aortic lymphadenectomies, up to the left renal vein. The results of this staging procedure and its indications are discussed. In all of the cases, the radical removal of the pathologic adnexa is indicated, along with the complete peritoneal and retroperitoneal staging. While fertility-sparing surgery (avoiding hysterectomy and contralateral adnexectomy, if possible) seems to be safe for young women, a TAH + BSO is the rule for the others. Adjuvant chemotherapy can be omitted in well-differentiated tumors with a negative staging operation, but currently it remains indicated in all other cases. Indeed, the ultimate goal in early stage ovarian carcinoma is to not impair by inadequate management the high chance of a cure.

Early experience of robotic-assisted laparoscopy for extraperitoneal para-aortic lymphadenectomy up to the left renal vein

OBJECTIVE To describe our early experience with robotic-assisted laparoscopy for extraperitoneal para-aortic lymphadenectomy up to the left renal vein, including Da Vinci robot positioning. METHODS Six patients underwent robotic-assisted laparoscopy using the Da Vinci apparatus. The patients included a man with a pT2 non-seminomatous germ cell tumour of the left testicle treated by chemotherapy with an incomplete response (mature teratoma), four women with locally advanced cervical cancer, and one case of bulky cancer of the vaginal cuff. The procedure was carried out using four port sites: one for the camera, one each for the no. 1 and no. 3 arms of the Da Vinci robot system, and one for the assistant. RESULTS AND CONCLUSION Robotic-assisted lymphadenectomy carried out using the Da Vinci system was safe and effective with a short learning period for an experienced oncological team. A larger prospective study is now required to evaluate this procedure further.

Vaginal evisceration after hysterectomy: the repair by a laparoscopic and vaginal approach with a omental flap

BACKGROUND Vaginal evisceration is generally repaired by vaginal or abdominal route. We describe two cases of vaginal evisceration using a combined laparoscopic and vaginal approach employing an omental flap. CASES Case 1: A radical abdominal hysterectomy was performed in a premenopausal patient for a FIGO IB1 cervical cancer. Four months later, she was found to have a vaginal cuff dehiscence which was repaired by a vaginal approach. Two months later, she had a vaginal cuff evisceration which was repaired using a combined laparoscopic and vaginal approach employing an omental flap with good success. Case 2: A postmenopausal woman who underwent an abdominal hysterectomy and pelvic lymphadenectomy for a FIGO IB endometrial cancer was noted to have a vaginal evisceration two months after primary surgery. This was also successfully repaired using a combined laparoscopic and vaginal approach employing an omental flap. CONCLUSION The combined laparoscopic and vaginal approach with omental flap is effective for repair of a vaginal cuff dehiscence with bowel evisceration. The addition of laparoscopy provides an opportunity for inspection of the small bowel, the peritoneal toilet, and mobilization of an omental flap.