Abstract Introduction Symptomatic postoperative lymphocysts (SPOLs) and lower-limb lymphedema (LLL) are probably underestimated complications of lymphadenectomy for gynecologic malignancies. Here, ...our objective was to evaluate the incidence and risk factors of SPOLs and LLL after pelvic and/or aortocaval lymphadenectomy for gynecologic malignancies. Methods Single-center retrospective study of consecutive patients who underwent pelvic and/or aortocaval lymphadenectomy for ovarian cancer, endometrial cancer, or cervical cancer between January 2007 and November 2008. The incidences of SPOL and LLL were computed with their 95% confidence intervals (95%CIs). Multivariate logistic regression was performed to identify independent risk factors for SPOL and LLL. Results We identified 88 patients including 36 with ovarian cancer, 35 with endometrial cancer, and 17 with cervical cancer. The overall incidence of SPOL was 34.5% (95%CI, 25–45) and that of LLL was 11.4% (95% confidence interval 95%CI, 5–18). Endometrial cancer was independently associated with a lower risk of SPOL (adjusted odds ratio aOR, 0.09; 95%CI, 0.02–0.44) and one or more positive pelvic nodes with a higher risk of SPOL (aOR, 4.4; 95%CI, 1.2–16.3). Multivariate logistic regression failed to identify factors significantly associated with LLL. Conclusion Complications of lymphadenectomy for gynecologic malignancies are common. This finding supports a more restrictive use of lymphadenectomy or the use of less invasive techniques such as sentinel node biopsy.
Abstract Objective Evaluate prognostic significance of low volume disease detected in sentinel nodes (SN) of patients with early stages cervical cancer. Although pathologic ultrastaging of SN allows ...for identification of low volume disease, including micro-metastasis and isolated tumor cells (ITC), in up to 15% of cases, prognostic significance of these findings is unknown. Methods A total of 645 records from 8 centers were retrospectively reviewed. Enrolled in our study were patients with early-stage cervical cancer who had undergone surgical treatment including SN biopsy followed by pelvic lymphadenectomy and pathologic ultrastaging of SN. Results Macrometastasis, micrometastasis, and ITC were detected by SN ultrastaging in 14.7%, 10.1%, and 4.5% patients respectively. False negativity of SN ultrastaging reached 2.8%. The presence of ITC was not associated with significant risk, both for recurrence free survival and overall survival. Overall survival was significantly reduced in patients with macrometastasis and micrometastasis; hazard ratio for overall survival reached 6.85 (95% CI, 2.59–18.05) and 6.86 (95% CI, 2.09–22.61) respectively. Presence of micrometastasis was an independent prognostic factor for overall survival in a multivariable model. Conclusion Presence of micrometastasis in SN in patients with early stage cervical cancer was associated with significant reduction of overall survival, which was equivalent to patients with macrometastasis. No prognostic significance was found for ITC. These data highlight the importance of SN biopsy and pathologic ultrastaging for the management of cervical cancer.
Pelvic lymph node dissection has been the standard of care for patients with early cervical cancer. Sentinel node (SN) mapping is safe and feasible and may increase the detection of metastatic ...disease, but benefits of omitting pelvic lymph node dissection in terms of decreased morbidity have not been demonstrated.
In an open-label study, patients with early cervical carcinoma (FIGO 2009 stage IA2 to IIA1) were randomly assigned to SN resection alone (SN arm) or SN and pelvic lymph node dissection (SN + PLND arm). SN resection was followed by radical surgery of the tumour (radical hysterectomy or radical trachelectomy). The primary end-point was morbidity related to the lymph node dissection; 3-year recurrence-free survival was a secondary end-point.
A total of 206 patients were eligible and randomly assigned to the SN arm (105 patients) or SN + PLND arm (101 patients). Most patients had stage IB1 lesion (87.4%). No false-negative case was observed in SN + PLND arm. Lymphatic morbidity was significantly lower in the SN arm (31.4%) than in the SN + PLND arm (51.5%; p = 0.0046), as was the rate of postoperative neurological symptoms (7.8% vs. 20.6%, p = 0.01, respectively). However, there was no significant difference in the proportion of patients with significant lymphoedema between the two groups. During the 6-month postoperative period, the difference in morbidity decreased over time. The 3-year recurrence-free survival was not significantly different (92.0% in SN arm and 94.4% in SN + PLND arm).
SN resection alone is associated with early decreased lymphatic morbidity when compared with SN + PLND in early cervical cancer.
•Randomised study comparing sentinel node biopsy and pelvic lymph node dissection.•Sentinel node biopsy alone is associated with decreased minor lymphatic morbidity.•No increased risk of recurrence while omitting pelvic lymph node dissection.
Aryl hydrocarbon receptor (AhR), or dioxin receptor, is a transcription factor that induces adaptive metabolic pathways in response to environmental pollutants. Recently, other pathways were found to ...be altered by AhR and its ligands. Indeed, developmental defects elicited by AhR ligands suggest that additional cellular functions may be targeted by this receptor, including cell migration and plasticity. Here, we show that dioxin-mediated activation of Ahr induces Nedd9/Hef1/Cas-L, a member of the Cas protein family recently identified as a metastasis marker. The Hef1 gene induction is mediated by two xenobiotic responsive elements present in this gene promoter. Moreover, using RNA interference, we show that Nedd9/Hef1/Cas-L mediates the dioxin-elicited changes related to cell plasticity, including alterations of cellular adhesion and shape, cytoskeleton reorganization, and increased cell migration. Furthermore, we show that both E-cadherin repression and Jun N-terminal kinases activation by dioxin and AhR also depend on the expression of Nedd9/Hef1/Cas-L. Our study unveils, for the first time, a link between pollutants exposure and the induced expression of a metastasis marker and shows that cellular migration and plasticity markers are regulated by AhR and its toxic ligands.
The objective of this study was to determine clinical, tumoral and surgical factors associated with successful bilateral sentinel lymph node mapping (SBM) in early-stage cervical cancer.
We performed ...an ancillary work on the data of two prospective trials on SLN biopsy for FIGO IA-IIA cervical cancer (SENTICOL I & II). Patients having Sentinel lymph node (SLN) mapping for early-stage cervical cancer were included between 2005 and 2012 from 28 French oncologic centers. SLN was detected by a combined labeling technique (blue and isotopic).
405 patients were included for analysis: SLNs were identified on at least one side of the pelvis in 381 patients (94.1%) and bilaterally in 326 patients (80.5%). The mean age was 45.4 years 22–85 years. Most patients had IB1 pathologic FIGO 2018 stage (81.3%) and squamous cell carcinoma (71%). Surgeries were mainly performed by minimally invasive approach (368 patients – 90.9%). By multivariate analysis, lower SBM rate was significantly associated with Age ≥70 years (ORa = 0.02, 95%CI = 0.001–0.28, p = 0.004), tumor size larger than 20 mm (ORa = 0.46,95%CI = 0.21–0.99, p = 0.048) and Body-mass index higher than 30 kg/m2 (ORa = 0.28, 95%CI = 0.12–0.65, p = 0.003). SBM rate was significantly higher in high skills centers (>5patients/year) (ORa = 8.05, 95%CI = 2.06–31.50, p = 0.003) and in SENTICOL II (2009–2012) compared to SENTICOL I (2005–2007) (ORa = 2.6, 95%CI = 1.23–5.51, p = 0.01).
In early-stage cervical cancer, bilateral SLN detection rates is lower in patients aged more than 70years, patients with BMI≥30 kg/m2 and larger tumor ≥20 mm whereas stronger experience of SLN biopsy technique improves bilateral SLN detection.
•Bilateral detection is required to increase sensitivity and decrease false-negative rate of sentinel lymph node biopsy.•Obesity may decrease bilateral detection of sentinel lymph nodes.•Bilateral detection of sentinel lymph nodes is lower in patients aged more than 70 years.•Failure of bilateral detection of sentinel lymph nodes is more frequent with tumor size larger than 20 mm.•Experience and higher surgical skills improved sentinel lymph nodes detection.
The purpose of this study was to describe sentinel lymph nodes (SLN) topography in patients with early-stage cervical cancer and to determine factors associated with atypical lymphatic drainage ...pathway (LDP).
We analyzed the data of two prospective multicentric trials on SLN biopsy for cervical cancer (SENTICOL I and II) in women undergoing surgery for early-stage cervical cancer. SLN detection was realized with a combined labeling technique (Patent blue and radioactive tracer). Patients having bilateral SLN detection were included. Univariate and Multivariate analysis were performed by patients and by side to assess clinical and pathologic factors that may predict atypical LDP.
Between January 2005 and July 2012, 326 patients with 1104 intraoperative detected SLNs fulfilled the inclusion criteria. The SLNs were mainly located in the interiliac or external iliac area in 83.2%. The other localizations were: 9.2% in the common iliac area, 3.9% in the parametrium, 1.6% in the promontory area, 1.5% in the paraaortic area and 0.5% in other areas. Thirty-five patients (10.7%) had atypical SLN without SLN in typical area on one or both sides. In multivariate analysis, tumor size ≥20 mm appeared as an independent factor of having at least one exclusive atypical LDP (ORa = 3.95 95%CI = 1.60–9.78, p = 0.003). Multiparity decreased significantly the probability of having at least one exclusive atypical LDP (ORa = 0.16 95%CI = 0.07–0.39, p < 0.0001).
Tumor size larger than 20 mm and nulliparity increase the risk of having exclusive atypical LDP in early-stage cervical cancer.
•Sentinel lymph nodes are mostly found in the interiliac and external iliac area.•Atypical topography of sentinel lymph nodes concerns up to 24.5% of patients.•Sentinel lymph nodes in atypical areas are more frequent with tumor size ≥20 mm.•Multiparity may have an impact on uterine lymphatic drainage.•Sentinel lymph node biopsy may detect metastatic nodes in aberrant topography.
Imaging is involved in the management of uterine cervical cancer with several objectives: 1/to assess local and lymph node extension of the initial disease; 2/evaluate treatment response to ...conservative therapy; 3/detect recurrences. Pelvic MRI is the first-line examination in all these indications. It is the key element for delineation after image fusion when the indication of chemoradiation therapy is made. It is also essential for guiding the placement of applicators and optimising the dosimetry of brachytherapy. The diffusion-weighted acquisition is a sequence sensitive to the motion of water molecules. It allows distinguishing water molecules with free diffusion from water molecules with diffusion restricted by obstacles such as cell membranes or the cytoskeleton. The diffusion is thus connected to the cellularity of the explored tissue, and the cancers, being hypercellular, will present a high signal. It thus provides additional information thanks to a high contrast between the tumour and the surrounding tissues, facilitating detection, evaluation of the volume and extent of the disease.
L’imagerie intervient dans la prise en charge du cancer du col utérin avec plusieurs objectifs : 1/faire le bilan d’extension locale et ganglionnaire de la maladie initiale ; 2/évaluer la réponse au traitement conservateur ; 3/détecter les récidives. L’IRM pelvienne est l’examen de première intention dans toutes ces indications. C’est l’élément clef de la délinéation après fusion d’image lorsque l’indication d’une chimioradiothérapie est posée. Elle est aussi indispensable pour guider la mise en place des applicateurs et optimiser la dosimétrie de la curiethérapie. L’acquisition pondérée en diffusion est une séquence sensible aux mouvements des molécules d’eau. Elle permet de distinguer les molécules d’eau en mouvement dont la diffusion est libre des molécules d’eau dont la diffusion est restreinte par des obstacles tels que les membranes cellulaires ou le cytosquelette. La diffusion est donc reliée à la cellularité du tissu exploré, et les cancers, hypercellulaires, seront en franc hypersignal. Elle apporte ainsi des informations supplémentaires grâce à un contraste élevé entre la tumeur et les tissus environnants, facilite la détection, l’évaluation du volume et de l’extension de la maladie.
Rare ovarian tumors represent >20% of all ovarian cancers. Given the rarity of these tumors, natural history, prognostic factors are not clearly identified. The extreme variability of patients (age, ...histological subtypes, stage) induces multiple and complex therapeutic strategies.
Since 2011, a national network with a dedicated system for referral, up to 22 regional and three national reference centers (RC) has been supported by the French National Cancer Institute (INCa). The network aims to prospectively monitor the management of rare ovarian tumors and provide an equal access to medical expertise and innovative treatments to all French patients through a dedicated website,www.ovaire-rare.org.
Over a 5-year activity, 4612 patients have been included. Patients’ inclusions increased from 553 in 2011 to 1202 in 2015. Expert pathology review and patients’ files discussion in dedicated multidisciplinary tumor boards increased from 166 cases in 2011 (25%) to 538 (45%) in 2015. Pathology review consistently modified the medical strategy in 5–9% every year. The rate of patients’ files discussed in RC similarly increased from 294 (53%) to 789 (66%). An increasing number (357 in 5 years) of gynecologic (non-ovarian) rare tumors were also registered by physicians seeking for pathological or medical advice from expert tumor boards.
Such a nation-wide organization for rare gynecological tumors has invaluable benefits, not only for patients, but also for epidemiological, clinical and biological research.
Abstract Background Two thirds of node-positive breast cancer patients have limited pN1 disease and could benefit from a less extensive axillary lymph node dissection (ALND). Methods 172 breast ...cancers patients requiring an ALND were prospectively enrolled in the Sentibras Protocol of Axillary Reverse Mapping (ARM). Radioisotope was injected in the ipsilateral hand the day before surgery. ALND was standard. Removed lymph nodes were classified into non radioactive nodes and radioactive nodes (ARM nodes). Among ARM nodes, nodes located in the upper outer part of the axilla, above the second intercostal brachial nerve and lateral to the lateral thoracic vein were identified as "zone D ARM nodes". The main objective was: feasibility of identification of the zone D ARM nodes. Secondary objectives were: metastatic involvement and lymphedema rate. Results 100% of patients had ARM nodes identified. The "zone D ARM nodes" were identified in 92 % of cases. The rate of metastatic nodes was 60% in the all cohort, 31% in ARM nodes and 9 % in zone D ARM nodes. Among those, metastatic rate was 6% in patients undergoing ALND for a positive sentinel node biopsy, 6% in case of primary ALND versus 14% after neo-adjuvant chemotherapy (p<0.05). After 34 months of median follow up, 27 % of interviewed patients had a lymphedema. Conclusion The ARM technique reliably identifies the "zone D ARM nodes". These nodes can also easily be identified using knowledge of axillary anatomy. In selected patients, a selective ALND sparing the zone D ARM nodes could be performed.
Rectosigmoid resection is often performed during cytoreductive surgery for ovarian cancer, to achieve the goal of no residual tumour. Here, we evaluated the morbidity associated with rectosigmoid ...resection and the underlying risk factors.
We retrospectively assessed consecutive patients managed with rectosigmoid resection during cytoreductive surgery for ovarian cancer at our centre in Paris, France, between 2005 and 2013. All previously identified risk factors were analysed. Major complications were defined as grade III-IV in the Clavien-Dindo classification.
Of 228 patients, 116 had primary and 112 interval surgery; 43/228 18.9%; experienced major complications, and these were more common after primary surgery 24.1% vs. 13.4%, p = .04. The 69 patients who had rectosigmoid resection 33 primary vs. 36 interval surgery, p = .32 had a higher morbidity rate compared to the other patients 30.4% vs. 14.6%, p = .006. The anastomotic leakage rate was 2.89%. By multivariate logistic regression, independent risk factors for morbidity were postmenopausal status adjusted odds ratio (aOR), 13.7; 95% confidence interval (95%CI), 1.2;161.9, surgery after neoadjuvant chemotherapy aOR, 4.4; 95%CI, 1.1;18.8, and peritoneal stripping of the left; paracolic gutter aOR, 11.3; 95%CI, 2.3;54.3.
The morbidity of rectosigmoid resection during cytoreductive surgery for ovarian cancer seems acceptable. Ileostomy does not seem associated with a lower risk of major complications or adjuvant bevacizumab with a higher complication rate.
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