Impact of preoperative brachytherapy followed by radical hysterectomy in stage IB2 (FIGO 2018) cervical cancer: An analysis of SENTICOL I-II trials.

INTRODUCTION: The goal of this study was to compare the outcomes of preoperative brachytherapy followed by radical surgery versus radical surgery alone in cervical cancer with tumor between 2 and 4 cm (FIGO 2018 IB2). MATERIAL AND METHODS: SENTICOL I and SENTICOL II were two French prospective multicentric trials evaluating sentinel node biopsy in early-stage cervical cancer between 2005 and 2012. Preoperative brachytherapy (low-dose rate or pulse-dose rate at the dose of 60Gy) could be performed 6 to 8 weeks prior to the radical hysterectomy, at the discretion of each center. SENTICOL I and SENTICOL II cohorts were retrospectively analysed to compare the outcomes of preoperative brachytherapy or upfront surgery in patients with IB2 cervical tumor. RESULTS: A total of 104 patients were included: 55 underwent upfront radical hysterectomy and 49 underwent preoperative brachytherapy followed by radical hysterectomy. Patients with preoperative brachytherapy were more likely to have no residual disease (71.4% vs. 25.5%, p < 0.0001) and to be defined as low risk according to Sedlis criteria (83.3% vs. 51.2%, p < 0.0001). Adjuvant treatments were required less frequently in case of preoperative brachytherapy (14.3% vs. 54.5%, p < 0.0001). Patients with preoperative brachytherapy experienced more postoperative complications grade ≥ 3 (24.5% vs. 9.1%, p = 0.03). Patients with preoperative brachytherapy had better 5-year disease-free survival compared to patients who underwent surgery alone, 93.6% and 74.4% respectively (p = 0.04). CONCLUSION: Although preoperative brachytherapy was significantly associated with more severe postoperative complications, better pathologic features were obtained on surgical specimens and led to a better 5-year disease-free survival in IB2 cervical cancer.

Diagnostic dilemma between angular and interstitial ectopic pregnancy: 3D ultrasound features.

Angular pregnancy is a rare entity which is commonly confused with interstitial or cornual pregnancies. A lack of consensus about the specific ultrasound features of these 3 entities leads to inappropriate interchange between them among the literature. An angular pregnancy should be considered as a potentially viable intra-uterine eccentric pregnancy as it might be carried to term and result in a live-born baby whereas interstitial or cornual pregnancies should be considered as ectopic pregnancies which should be interrupted. We report here two cases of women at 8 weeks of pregnancy with an angular pregnancy diagnosed by vaginal 2D and 3D ultrasound and discuss about specific ultrasound features and alternative imaging modalities to distinguish it from interstitial and cornual pregnancies.

Diagnostic value of frozen section examination of sentinel lymph nodes in early-stage cervical cancer at the time of ultrastaging.

OBJECTIVES: We aimed to assess the diagnostic value of frozen-section pathologic examination (FSE) of sentinel lymph nodes (SLN) in patients with early-stage cervical cancer. METHODS: Two French prospective multicentric database on SLN biopsy for cervical cancer (SENTICOL I and II) were analysed. Patients with IA to IIA1 2018 FIGO stage, who underwent SLN biopsy with both FSE and ultrastaging examination were included. RESULTS AND DISCUSSION: Between 2005 and 2012, 313 patients from 25 centers fulfilled the inclusion criteria. Metastatic involvement of SLN was diagnosed in 52 patients (16.6%). Macrometastases, micrometastases and isolated tumor cells (ITCs) were found in 27, 12 and 13 patients respectively. Among the 928 SLNs analysed, FSE identified 23 SLNs with macrometastases in 20 patients and 5 SLNs with micrometastases in 2 patients whereas no ITCs were identified. Ultrastaging of negative SLNs by FSE found macrometastases, micrometastases and ITCs in additional 7, 11 and 17 SLNs. Ultrastaging increased significantly the rate of patients with positive SLN from 7% to 16.6% (p < 0.0001). The sensitivity and the negative predictive value of FSE were 42.3% and 89.7% respectively or 56.4% and 94.1% if ITCs were excluded. False-negative cases were more frequent with tumor size ≥ 20 mm (OR = 4.46, 95%IC = [1.45-13.66], p = 0.01) and preoperative brachytherapy (OR = 4.47, 95%IC = [1.37-14.63], p = 0.01) and less frequent with patients included in higher volume center (>5 patients/year) (OR = 0.09, 95%IC = [0.02-0.51], p = 0.01). CONCLUSIONS: FSE of SLN had a low sensitivity for detecting micrometastases and ITCs and a high negative predictive value for SLN status. Clinical impact of false-negative cases has to be assessed by further studies.

Risk factors for failure of bilateral sentinel lymph node mapping in early-stage cervical cancer.

BACKGROUND: 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. METHODS: 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). RESULTS: 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). CONCLUSIONS: 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.

Predictive factors of unexpected lymphatic drainage pathways in early-stage cervical cancer.

OBJECTIVES: 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). METHODS: 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. RESULTS: 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). CONCLUSIONS: Tumor size larger than 20 mm and nulliparity increase the risk of having exclusive atypical LDP in early-stage cervical cancer.

Predictive factors of severe perioperative morbidity of radical hysterectomy with lymphadenectomy in early-stage cervical cancer: A French prospective multicentric cohort of 248 patients.

OBJECTIVE: The purpose of this study was to assess the postoperative morbidity after radical hysterectomy (RH) for early-stage cervical cancer and to determine risk factors of severe perioperative morbidity. METHODS: Data of two prospective trials on sentinel node biopsy for cervical cancer (SENTICOL I & II) were analysed. Patients having a radical hysterectomy were included between 2005 and 2012 from 25 French oncologic centers. Postoperative complications were prospectively recorded in a pre-specified analysis. RESULTS: 248 patients met the inclusion criteria. The median age was 44.5 years [25-85]. 88.7% of patients had a stage IB1 disease. There were 71.4% epidermoid carcinomas and 25% adenocarcinomas. 125 patients (50.4%) had a laparoscopic-assisted vaginal RH, 88 patients (35.5%) had a total laparoscopic RH, 26 patients (10.5%) had an open RH and 9 patients (3.6%) had a robotic-assisted RH. Sixteen patients (6.4%) had intraoperative complications. On a multivariate analysis, intraoperative complications were significantly associated with BMI >30 kg/m2. The urinary, lymphovascular and neurologic complications rates were respectively 34.3%, 20.6% and 19.8%. 31 patients (12.5%) had severe postoperative complications (Clavien-Dindo ≥ 3 or CTCAE ≥ 3). On multivariate analysis, severe postoperative complications were associated with parametrial involvement, preoperative brachytherapy and inclusion in low surgical skills center. CONCLUSIONS: This study based on prospective data showed that RH has low severe postoperative complications. The main complications were urinary infections and lower limb lymphedema. Patients with early-stage cervical cancer should be referred to expert center to ensure best surgical outcomes.

Precaval positive sentinel lymph node with bilateral negative pelvic sentinel lymph node in low-risk endometrial cancer patient.

We here describe a case report of a positive precaval sentinel lymph node with negative pelvic sentinel lymph node in a patient with endometrial cancer. A 45-years-old woman was diagnosed with a grade 2 endometrioid carcinoma of the endometrium. She was treated with a hysterectomy and bilateral salpingo-oophorectomy, associated with dissection of sentinel lymph nodes (SLNs). We detected bilateral external and common bilateral iliac nodes and one precaval node. At pathological examination the pelvic nodes were non-metastatic, but the precaval node was positive. In this patient, sentinel node biopsy improved risk-assessment and adjuvant treatment.

What about sentinel lymph node biopsy for early breast cancer during pregnancy?

Pregnancy-associated breast cancer is rare, but this clinical situation arises in 1/10,000-1/3000 pregnancies. In patients presenting an early-stage breast tumor devoid of clinically pathological lymph node, sentinel lymph node (SLN) biopsy has not yet been validated as a routine procedure for pregnant women due to the lack of data in the literature. The blue dye injection is not recommended because of 2% theoretical risk of anaphylactic shock. Several studies have shown that Tc99m injection at conventional dose between 12.1 and 18.5MBq exposed the fetus to an irradiation between 0.011 and 0.0245mSv much below the 50mSv recommended threshold. As evidenced by lymphoscintigraphy scans, the dose of injected Tc99m is localized at the injection site and in the SLN. According to the literature, the SLN technique does not seem to impact the fetal or obstetrical prognosis. Studies involving larger cohorts are required to confirm these data and to indicate this technique in pregnant women. Considering the benefit for the patient and the low risk incurred on both fetal and obstetrical levels, it appears reasonable to discuss the indication of SLN on a case-by-case basis in multidisciplinary oncologic meetings.

Isolated fallopian tube metastasis from colorectal cancer: ultrasonographic features.

We present here the first-reported case of tubal metastasis from colorectal cancer diagnosed by a preoperative pelvic ultrasound. A 53-year-old woman suffering from vaginal discharge was referred to us 2 years after she underwent a partial colectomy for adenocarcinoma. The pelvic ultrasound examination revealed a right pelvic mass of 52 × 24 × 38 mm, independent of the right ovary, which was apparently unaffected. A right salpingo-oophorectomy was performed and the definitive histopathology examination showed a recurrence of the initial adenocarcinoma with a right tubal metastasis. The eventuality of such an unusual site of metastasis should be remembered.

[Anatomical consideration for the technique of nerve-sparing during radical hysterectomy for cervical cancer]. / Bases anatomiques et principe du nerve-sparing au cours de l'hystérectomie radicale pour cancer du col utérin.

Radical hysterectomy (RH) is an effective treatment for early-stage cervical cancer IA2 to IIA1 but RH is often associated with several significant complications such as urinary, anorectal and sexual dysfunction due to pelvic nerve injuries. Pelvic autonomic nerves including the superior hypogastric plexus (SHP), hypogastric nerves (HN), pelvic splanchnic nerves (PSN), sacral splanchnic nerves (SSN), inferior hypogastric plexus (IHP) and efferent branches of the IHP. We aimed to precise the neuroanatomy of the female pelvis in order to provide key-points of surgical anatomy to improve NSRH for cervical cancer. The SHP could be injured during periaortic lymph node dissection and its preservation necessitates an approach on the right side of the aorta and a blunt dissection of the promontory before lomboaortic lymphadenectomy. Injuries to HN can occur during the resection of USL at the posterior pelvic wall and of rectovaginal ligaments and to preserve HN only the medial fibrous part of the uterosacral ligament should be resected. The middle rectal artery, the deep uterine vein and the ureter should be identified to preserve PSN and IHP during resection of paracervix. Vesical branches can be preserved by blunt dissection of the posterior layer of the vesicouterine ligament after identifying the inferior vesical vein. In most of cases, NSRH for cervical cancer can be performed. Anatomical landmarks as middle rectal artery, deep uterine vein, inferior vesical vein and ureter and the respect of nervous part of uterine ligament and of parametrium provide to surgeon a safe preservation of pelvic innervation without compromising oncological outcomes.

[3D modeling of the female pelvis by Computer-Assisted Anatomical Dissection: Applications and perspectives]. / Modélisation anatomique 3D du pelvis féminin par dissection anatomique assistée par ordinateur : applications et perspectives.

OBJECTIVES: To achieve a 3D vectorial model of a female pelvis by Computer-Assisted Anatomical Dissection and to assess educationnal and surgical applications. MATERIALS AND METHOD: From the database of "visible female" of Visible Human Project(®) (VHP) of the "national library of medicine" NLM (United States), we used 739 transverse anatomical slices of 0.33mm thickness going from L4 to the trochanters. The manual segmentation of each anatomical structures was done with Winsurf(®) software version 4.3. Each anatomical element was built as a separate vectorial object. The whole colored-rendered vectorial model with realistic textures was exported in 3Dpdf format to allow a real time interactive manipulation with Acrobat(®) pro version 11 software. RESULTS: Each element can be handled separately at any transparency, which allows an anatomical learning by systems: skeleton, pelvic organs, urogenital system, arterial and venous vascularization. This 3D anatomical model can be used as data bank to teach of the fundamental anatomy. CONCLUSION: This 3D vectorial model, realistic and interactive constitutes an efficient educational tool for the teaching of the anatomy of the pelvis. 3D printing of the pelvis is possible with the new printers.

[Ultrasonographic features in the preoperative diagnosis of primitive fallopian tube carcinoma]. / Apport de l'échographie dans le diagnostic pré-opératoire des tumeurs malignes primitives de la trompe de Fallope.

OBJECTIVES: To review the characteristic ultrasound features of primary fallopian tube carcinoma (PFTC) and its relationship to the clinical history in order to establish specific findings useful for the preoperative diagnosis. METHOD: An extensive review of the current literature was done on Medline via PubMed by using the following keywords: "primary fallopian tube cancer", "tubal cancer", "adnexal malignancy mass" and "ultrasound". RESULTS: PFTC corresponds to complex, sausage-shaped structures or cystic adnexal masses. A thick and an irregular capsule are in favour of a malignant lesion. Three-dimensional ultrasound is superior to 2D ultrasound for the detection of tubal wall irregularities such as papillary projections or pseudosepta who were suggestive of tubal malignancy and allows a better assessment of the extent of tumor infiltration through the capsule. Neovascularization with low resistance indices are typical of tubal malignancy. Three-dimensional power Doppler sonography acutely detected structural abnormalities of the malignant tumor vessels which are randomly dispersed within the papillary projections. Intra-uterine collection and peritumoral fluid are often found but ascite could be also an indirect proof of peritoneal carcinosis. CONCLUSION: Sausage-shaped structures or cystic adnexal masses associated with imaging findings such as papillary projections and neovascularization with low resistance indices are in favour of PFTC. A standardized terminology, high-frequency and 3D power Doppler could improve diagnostic performance by allowing a better assessment of tubal wall and chaotic vessels architecture of these tumors.

[The dorsal nerve of the clitoris: surgical applications]. / Le nerf dorsal du clitoris : de l'anatomie à la chirurgie reconstructrice du clitoris.

OBJECTIVES: To describe the course of the dorsal nerve of the clitoris (DNC) to better define its anatomy in the human adult and to help surgeons to avoid iatrogenic injury during surgical procedures. METHOD: An extensive review of the current literature was done on Medline via PubMed by using the following keywords: "anatomie du clitoris", "anatomy of clitoris", "nerf dorsal du clitoris", "dorsal nerve of clitoris", "réparation clitoridienne", "transposition clitoridienne", "surgery of the clitoris", "clitoridoplasty". This review analyzed dissection, magnetic resonance imaging, 3-dimensional sectional anatomy reconstruction and immuno-histochemical studies. RESULTS: The DNC comes from the pudendal nerve. He travels from under the inferior pubis ramus to the posterosuperior edge of the clitoral crus. The DNC reappears under the pubic symphysis and enters the deep component of the suspensory ligament. He runs on the dorsal face of the clitoral body at 11 and 1 o'clock. Distally, he gives many nervous ramifications, runs along the tunica and enters the glans. CONCLUSION: The NDC might be surgically injured (i) under the pubic symphysis, at the union of the two crus of clitoris and (ii) on the dorsal surface of the clitoral body. The pathway of the DNC on the dorsal face of the clitoris permits to approach the ventral face of the clitoris without risk of iatrogenic injuries. The distance between the pubic symphysis and the DNC implies that the incision should be done just under the pubic symphysis. Distally, the dissection of the DNC next the glands appears as dangerous and impossible, considering that the DNC is too close to the glandular tissues.