Lymphocele following lymph node dissection in cervical and endometrial cancer: A systematic review and meta-analysis.

OBJECTIVES: The purpose of this systematic review and meta-analysis was to evaluate the proportion and risk factors of lymphoceles and symptomatic lymphoceles after PLND in early-stage cervical and early-stage high or high-intermediate risk endometrial cancer. METHODS: Studies reporting on the proportion of lymphocele after PLND were conducted in PubMed, Embase and Cochrane Library. Retrieved studies were screened on title/abstract and full text by two reviewers independently. Quality assessment was conducted using the Newcastle Ottowa Scale and the Cochrane risk-of-bias tool. Proportion of lymphocele and possible risk factors were pooled through random-effects meta-analyses. RESULTS: From the 233 studies retrieved, 24 studies were included. The pooled proportion of lymphocele was 14% and of symptomatic lymphocele was 3%. Routinely performing diagnostics was associated with a significantly higher proportion of lymphocele compared to diagnostics performed on indication (21% versus 4%, p < 0.01). Laparotomic surgical approach led to a significantly higher proportion of lymphoceles than laparoscopic surgical approach (18% versus 7%, p = 0.05). The proportion of lymphocele was significantly higher when >15% of the study population underwent additional paraaortic lymph node dissection (PAOLND) opposed to <15% (15% versus 3%, p < 0.01). A mean number of lymph nodes dissected of <21 resulted in a significantly higher pooled proportion of lymphoceles opposed to when the mean number was 21 or higher (19% versus 5%, p = 0.02). Other risk factors analysed were BMI, lymph node metastasis, adjuvant radiotherapy and follow up. There was no sufficient data to detect significant risk factors for the development of symptomatic lymphoceles. CONCLUSION: The pooled proportion of lymphocele was 14% of which symptomatic lymphoceles occurred in 3%. Significant risk factors for the total proportion of lymphoceles were laparotomic approach, decreased number of lymph nodes dissected and additional PAOLND.

Value of routine cytokeratin immunohistochemistry in detecting low volume disease in cervical cancer.

OBJECTIVE: In cervical cancer, sentinel lymph nodes (SLNs) are processed according to the pathological ultrastaging protocol. According to current guidelines, immunohistochemistry with pancytokeratin antibodies is performed in addition to step sectioning with hematoxylin and eosin (H&E), aiding the detection of low volume disease (micrometastasis and isolated tumor cells (ITC)). We studied the added clinical value, and costs, of routine immunohistochemistry (IHC). METHODS: We retrospectively included all FIGO stage IA-IIA1 cervical cancer patients who had undergone SLN procedures at UMC Utrecht from 2008 to 2020. Pathological data were derived from the Dutch Pathology Registry (PALGA) including SLN tumor status and number of slides stained with IHC. RESULTS: In total 234 cervical cancer patients were included. In the 516 surgically resected SLN specimens, 630 SLNs were discovered by the pathologist. Hereof, 579 SLNs from 211 patients were routinely processed with IHC. IHC identified three patients with micrometastasis and five patients with ITC undetected with H&E staining. Thereby, IHC significantly increased the number of patients with low volume disease from 11 (5.3%) to 19 patients (9.1%) (p = 0.04). To achieve this, 3791 slides were stained with IHC at an estimated additional cost of €94,775. In 1.4% (95% CI 0.3%-4.3%) of patients routine use of IHC adjusted the adjuvant treatment. CONCLUSIONS: Routine use of IHC increases detection of low volume disease in cervical cancer SLNs compared to step sectioning with H&E alone by nearly 4%, with an impact on therapeutic strategy-decisions in about 1% of patients. In view of the high associated costs, cost-effectiveness of routine IHC is questionable.

The feasibility of folate receptor alpha- and HER2-targeted intraoperative fluorescence-guided cytoreductive surgery in women with epithelial ovarian cancer: A systematic review.

BACKGROUND: Epithelial ovarian cancer (EOC) is often diagnosed late, with a 5-year relative survival of 30.2% for patients with metastatic disease. Residual disease following cytoreductive surgery is an important predictor for poor survival. EOC is characterized by diffuse peritoneal metastases and depositions of small size, challenging a complete resection. Targeted fluorescence imaging is a technique to enhance tumor visualization and can be performed intraoperatively. Folate receptor alpha (FRα) and human epidermal growth factor receptor 2 (HER2) are overexpressed in EOC in 80% and 20% of the cases, respectively, and have been previously studied as a target for intraoperative imaging. OBJECTIVE: To systematically review the literature on the feasibility of FRα and HER2 targeted fluorescence-guided cytoreductive surgery (FGCS) in women with EOC. METHODS: PubMed and Embase were searched for human and animal studies on FGCS targeting either HER2 or FRα in either women with EOC or animal models of EOC. Risk of bias and methodological quality were assessed with the SYRCLE and MINORS tool, respectively. RESULTS: All animal studies targeting either FRα or HER2 were able to detect tumor deposits using intraoperative fluorescence imaging. One animal study targeting HER2 compared conventional cytoreductive surgery (CCS) to FGCS and concluded that FGCS, either without or following CCS, resulted in statistically significant less residual disease compared to CCS alone. Human studies on FGCS showed an increased detection rate of tumor deposits. True positives ranged between 75%-77% and false positives between 10%-25%. Lymph nodes were the main source of false positive results. Sensitivity was 85.9%, though only reported by one human study. CONCLUSION: FGCS targeting either HER2 or FRα appears to be feasible in both EOC animal models and patients with EOC. FGCS is a promising technique, but further research is warranted to validate these results and particularly study the survival benefit.

The influence of learning curve of robot-assisted laparoscopy on oncological outcomes in early-stage cervical cancer: an observational cohort study.

OBJECTIVE: To investigate the learning curve of robot-assisted laparoscopy in early-stage cervical cancer and quantify impact on oncological outcomes. DESIGN: Observational cohort study. SETTING: Tertiary referral centre with one surgical team. POPULATION: All women with early-stage cervical cancer treated consecutively with robot-assisted laparoscopy between 2007 and 2017. METHODS: With multivariate risk-adjusted cumulative sum analysis (RA-CUSUM), we assessed the learning curve of robot-assisted laparoscopy of a single surgical team based on cervical cancer recurrence. Subsequently, a survival analysis was conducted comparing oncological outcomes of women treated during different phases of the learning curve. MAIN OUTCOME MEASURES: Surgical proficiency based on recurrence, survival rates in the different learning phases. RESULTS: One hundred and sixty-five women with cervical cancer underwent robot-assisted laparoscopy, with a median follow up of 57 months (range 3-132 months). The RA-CUSUM analysis demonstrated two phases of the learning curve: a learning phase of 61 procedures (group 1) and an experienced phase representing the 104 procedures thereafter (group 2). The 5-year disease-free survival was 80.2% in group 1 and 91.1% in group 2 (P = 0.040). Both the 5-year disease-specific survival and overall survival significantly increased after the learning phase. CONCLUSION: The learning phase of robot-assisted laparoscopy in early-stage cervical cancer in this institutional cohort is at least 61 procedures, with higher survival rates in the women treated thereafter. The learning curve of robot-assisted laparoscopy affects oncological outcomes and warrants more attention in the design of future studies. TWEETABLE ABSTRACT: The learning curve of robot-assisted laparoscopy in early-stage cervical cancer affects oncological outcomes and warrants more attention.

Proton MRS of cervical cancer at 7 T.

The differentiation grade of cervical cancer is histologically assessed by examining biopsies or surgical specimens. MRS is a highly sensitive technique that images tissue metabolism and can be used to increase the specificity of tissue characterization in a non-invasive manner. We aim to explore the feasibility of using in vivo 1 H-MRS at 7 T in women with cervical cancer to study tissue fatty acid composition. 10 women with histologically proven Stage IB1-IIB cervical cancer were scanned with a whole-body 7 T MR system with a multi-transmit system and an internal receive only monopole antenna. A STEAM sequence was used to obtain 1 H-MRS data. Fatty acid resonances were fitted with Lorentzian curves and the 2.1 ppm/1.3 ppm ratios were calculated. 1 H-MRS data showed fatty acid signals resonating at 2.1 ppm, 1.9 ppm, 1.5 ppm, 1.3 ppm and 0.9 ppm. Mean 2.1/1.3 ppm ratios were 0.019 ± 0.01, 0.021 ± 0.006, 0.12 ± 0.089 and 0.39 ± 0.27 for normal, Grade I, Grade II and Grade III groups respectively. Poorly differentiated tumor tissue (Grade III) showed elevated fatty acid ratios when compared with the well differentiated tumor (Grade I) or normal tissue. 1 H-MRS in cervical cancer at 7 T is feasible and individual fatty acid signals were detected. In addition, poorly differentiated tumors show more fatty acid unsaturation. The 2.1 ppm/1.3 ppm ratio has potential for tumor characterization in a non-invasive manner for uterine cervical cancer.

Boosting the SNR by adding a receive-only endorectal monopole to an external antenna array for high-resolution, T2 -weighted imaging of early-stage cervical cancer with 7-T MRI.

The aim of this study was to investigate the signal-to-noise ratio (SNR) gain in early-stage cervical cancer at ultrahigh-field MRI (e.g. 7 T) using a combination of multiple external antennas and a single endorectal antenna. In particular, we used an endorectal monopole antenna to increase the SNR in cervical magnetic resonance imaging (MRI). This should allow high-resolution, T2 -weighted imaging and magnetic resonance spectroscopy (MRS) for metabolic staging, which could facilitate the local tumor status assessment. In a prospective feasibility study, five healthy female volunteers and six patients with histologically proven stage IB1-IIB cervical cancer were scanned at 7 T. We used seven external fractionated dipole antennas for transmit-receive (transceive) and an endorectally placed monopole antenna for reception only. A region of interest, containing both normal cervix and tumor tissue, was selected for the SNR measurement. Separated signal and noise measurements were obtained in the region of the cervix for each element and in the near field of the monopole antenna (radius < 30 mm) to calculate the SNR gain of the endorectal antenna in each patient. We obtained high-resolution, T2 -weighted images with a voxel size of 0.7 × 0.8 × 3.0 mm3 . In four cases with optimal placement of the endorectal antenna (verified on the T2 -weighted images), a mean gain of 2.2 in SNR was obtained at the overall cervix and tumor tissue area. Within a radius of 30 mm from the monopole antenna, a mean SNR gain of 3.7 was achieved in the four optimal cases. Overlap between the two different regions of the SNR calculations was around 24%. We have demonstrated that the use of an endorectal monopole antenna substantially increases the SNR of 7-T MRI at the cervical anatomy. Combined with the intrinsically high SNR of ultrahigh-field MRI, this gain may be employed to obtain metabolic information using MRS and to enhance spatial resolutions to assess tumor invasion.

Surgical lymph node assessment in mucinous ovarian carcinoma staging: a systematic review and meta-analysis.

BACKGROUND: The proportion of women with mucinous ovarian carcinoma in whom nodal metastases are identified during staging remains unclear. OBJECTIVES: To review the literature on surgical lymph node assessment during staging of women diagnosed with mucinous ovarian carcinoma. SEARCH STRATEGY: A systematic search using synonyms of 'mucinous ovarian carcinoma' and 'lymph node assessment' was conducted in PubMed, Scopus, Embase and the Cochrane Library. SELECTION CRITERIA: When they covered ten or more mucinous ovarian carcinoma cases, staging surgery and minimally one of the following outcomes: prevalence of metastases, stage shift or survival data. DATA COLLECTION AND ANALYSIS: Studies were quality evaluated with the Cochrane risk-of-bias assessment tool for non-randomised studies of interventions. Outcomes were pooled using an inverse variance weighted random effects model. MAIN RESULTS: Sixteen studies were included. In 278 women with mucinous ovarian cancer suspected to be stage I-II, a pooled proportion of 0.8% (95% CI <0.1-2.9%) had lymph node metastases and were upstaged. In those suspected of stage I (n = 184), this proportion was 0.7% (95% CI <0.1-3.8%). No difference (P = 0.287) was found in metastases between sampling at 0.0% (95% CI 0.0-3.3%) and complete pelvic and/or para-aortic lymph node dissection at 1.2% (95% CI <0.1-4.2%). One study directly compared the survival of patients staged with and without lymph node dissection and reported no significant difference. CONCLUSIONS: Surgical lymph node assessment in women suspected of stage I-II mucinous ovarian carcinoma rarely identifies nodal metastases and consequently has no significant impact on staging. TWEETABLE ABSTRACT: Surgical lymph node assessment in women with stage I-II mucinous ovarian cancer rarely has staging consequences.

Oncological outcome and long-term complications in robot-assisted radical surgery for early stage cervical cancer: an observational cohort study.

OBJECTIVE: To report the oncological outcome and long-term complications of radical surgery by robot-assisted laparoscopy in early stage cervical cancer. DESIGN: Observational cohort study. SETTING: Tertiary referral centre. POPULATION: About 100 cervical cancer patients treated consecutively with robot-assisted radical surgery between 2008 and 2013. METHODS: Two gynaecological oncologists specialised in minimally invasive surgery performed all surgeries on a three/four-armed robotic system. Procedures consisted of pelvic lymph node dissection combined with a radical hysterectomy, radical vaginal trachelectomy or parametrectomy. MAIN OUTCOME MEASURES: Recurrence, survival and long-term complication rates. RESULTS: 104 robot-assisted laparoscopies were performed in 100 patients (stage IA1-IIB), with a median follow-up of 29.5 months (range 2.5-67.1 months). Thirteen cases were diagnosed with a loco-regional (8%), distant (4%) or combined (1%) recurrence at a median of 14.4 months (range 2.9-34.8 months). All mortality (7%) was cervical cancer-related and due to recurrent disease. Four recurrences receive palliative care and two are in complete remission. The overall 5-year progression-free and disease-specific survival rates are 81.4 and 88.7%, respectively. Frequent complications were lymphoedema (26%), lower urinary tract symptoms (19%), urinary tract infection (17%) and sexual disorders (9%). Five patients had a vaginal cuff dehiscence. No complication-related mortality occurred. CONCLUSION: The recurrence, survival and long-term complication rates of robot-assisted radical surgery for early stage cervical cancer in this cohort are reassuring concerning its continued clinical use.

CT, MRI and laparoscopy findings of a retroperitoneally herniated ovary causing acute abdominal pain.

We report a case of a young woman presenting with abdominal pain due to a rare and recurrent herniation of the ovary, to a retroperitoneal location lateral to the external iliac artery and directly dorsal to the iliopsoas muscle. Correlation between computed tomography, magnetic resonance imaging and laparoscopy is presented. The patient's complaints subsided after right oophoropexy. When aware, this diagnosis is easy to make and may allow symptomatic patients to be treated with laparoscopic oophoropexy.