Incidence of inguinofemoral lymph node metastases at the first local recurrence of vulvar cancer: a Dutch nationwide study.

BACKGROUND: Up to 40% of vulvar cancer patients present with local recurrence within 10 years of follow-up. An inguinofemoral lymphadenectomy (IFL) is indicated if not performed at primary treatment. The incidence and risk factors for lymph node metastases (LNM) at first local recurrence, however, are unclear. Our aim was to determine the incidence of LNM at first local recurrence, in relation to previous groin treatment and clinicopathological factors. METHODS: A multicenter cohort study including vulvar cancer patients with a first macroinvasive local recurrence after primary surgical treatment between 2000 and 2015 was conducted in the Netherlands. Groin status at local recurrence was defined as positive (N+), negative (N-) or unknown (N?) and based on histology, imaging and follow-up. Patient-, tumour- and treatment characteristics of primary and recurrent disease were analysed. RESULTS: Overall, 16.3% (66/404) had a N+ groin status at first local recurrence, 66.4% (268/404) N- and 17.3% (70/404) N? groin status. The incidence of a N+ groin status was comparable after previous SLN and IFL, 11.5% and 13.8%, respectively. A N+ groin status was related to tumour size (25 vs.12 mm; P < 0.001), depth of invasion (5 vs. 3 mm; P < 0.001) and poorly differentiated tumours (22.9 vs. 11.9%; P = 0.050) at local recurrence. CONCLUSIONS: The incidence of LNM at first local recurrence in vulvar cancer patients was 16.3%, and independent of previous type of groin surgery. In accordance with primary diagnosis, tumour size, depth of invasion, and tumour grade were significantly associated with a positive groin status.

HPV and DNA Methylation Testing in Urine for Cervical Intraepithelial Neoplasia and Cervical Cancer Detection.

PURPOSE: Biomarker detection in urine offers a potential solution to increase effectiveness of cervical cancer screening programs by attracting nonresponders. In this prospective study, the presence of high-risk human papillomavirus (hrHPV) DNA and the performance of DNA methylation analysis was determined for the detection of cervical cancer and high-grade cervical intraepithelial neoplasia (CIN2/3) in urine, and compared with paired cervicovaginal self-samples and clinician-taken cervical scrapes. EXPERIMENTAL DESIGN: A total of 587 samples were included from 113 women with cervical cancer, 92 women with CIN2/3, and 64 controls. Samples were tested for hrHPV DNA and five methylation markers. Univariate and multivariate logistic regression and leave-one-out cross-validation were used to determine the methylation marker performance for CIN3 and cervical cancer (CIN3+) detection in urine. Agreement between samples was determined using Cohen kappa statistics and the Spearman correlation coefficients. RESULTS: HrHPV presence was high in all sample types, 79% to 92%. Methylation levels of all markers in urine significantly increased with increasing severity of disease. The optimal marker panel (ASCL1/LHX8) resulted in an AUC of 0.84 for CIN3+ detection in urine, corresponding to an 86% sensitivity at a 70% predefined specificity. At this threshold 96% (109/113) of cervical cancers, 68% (46/64) of CIN3, and 58% (14/24) of CIN2 were detected. Between paired samples, a strong agreement for HPV16/18 genotyping and a fair to strong correlation for methylation was found. CONCLUSIONS: HrHPV DNA and DNA methylation testing in urine offers a promising solution to detect cervical cancer and CIN2/3 lesions, especially for women currently unreached by conventional screening methods.

Radiotherapy Versus Inguinofemoral Lymphadenectomy as Treatment for Vulvar Cancer Patients With Micrometastases in the Sentinel Node: Results of GROINSS-V II.

PURPOSE: The Groningen International Study on Sentinel nodes in Vulvar cancer (GROINSS-V)-II investigated whether inguinofemoral radiotherapy is a safe alternative to inguinofemoral lymphadenectomy (IFL) in vulvar cancer patients with a metastatic sentinel node (SN). METHODS: GROINSS-V-II was a prospective multicenter phase-II single-arm treatment trial, including patients with early-stage vulvar cancer (diameter < 4 cm) without signs of lymph node involvement at imaging, who had primary surgical treatment (local excision with SN biopsy). Where the SN was involved (metastasis of any size), inguinofemoral radiotherapy was given (50 Gy). The primary end point was isolated groin recurrence rate at 24 months. Stopping rules were defined for the occurrence of groin recurrences. RESULTS: From December 2005 until October 2016, 1,535 eligible patients were registered. The SN showed metastasis in 322 (21.0%) patients. In June 2010, with 91 SN-positive patients included, the stopping rule was activated because the isolated groin recurrence rate in this group went above our predefined threshold. Among 10 patients with an isolated groin recurrence, nine had SN metastases > 2 mm and/or extracapsular spread. The protocol was amended so that those with SN macrometastases (> 2 mm) underwent standard of care (IFL), whereas patients with SN micrometastases (≤ 2 mm) continued to receive inguinofemoral radiotherapy. Among 160 patients with SN micrometastases, 126 received inguinofemoral radiotherapy, with an ipsilateral isolated groin recurrence rate at 2 years of 1.6%. Among 162 patients with SN macrometastases, the isolated groin recurrence rate at 2 years was 22% in those who underwent radiotherapy, and 6.9% in those who underwent IFL (P = .011). Treatment-related morbidity after radiotherapy was less frequent compared with IFL. CONCLUSION: Inguinofemoral radiotherapy is a safe alternative for IFL in patients with SN micrometastases, with minimal morbidity. For patients with SN macrometastasis, radiotherapy with a total dose of 50 Gy resulted in more isolated groin recurrences compared with IFL.

Evaluation of treatment, prognostic factors, and survival in 198 vulvar melanoma patients: Implications for clinical practice.

OBJECTIVE: To identify clinicopathological characteristics, treatment patterns, clinical outcomes and prognostic factors in patients with vulvar melanoma (VM). MATERIALS & METHODS: This retrospective multicentre cohort study included 198 women with VM treated in eight cancer centres in the Netherlands and UK between 1990 and 2017. Clinicopathological features, treatment, recurrence, and survival data were collected. Overall and recurrence-free survival was estimated with the Kaplan-Meier method. Prognostic parameters were identified with multivariable Cox regression analysis. RESULTS: The majority of patients (75.8%) had localized disease at diagnosis. VM was significantly associated with high-risk clinicopathological features, including age, tumour thickness, ulceration, positive resection margins and involved lymph nodes. Overall survival was 48% (95% CI 40-56%) and 31% (95% CI 23-39%) after 2 and 5 years respectively and did not improve in patients diagnosed after 2010 compared to patients diagnosed between 1990 and 2009. Recurrence occurred in 66.7% of patients, of which two-third was non-local. In multivariable analysis, age and tumour size were independent prognostic factors for worse survival. Prognostic factors for recurrence were tumour size and tumour type. Only the minority of patients were treated with immuno- or targeted therapy. CONCLUSION: Our results show that even clinically early-stage VM is an aggressive disease associated with poor clinical outcome due to distant metastases. Further investigation into the genomic landscape and the immune microenvironment in VM may pave the way to novel therapies to improve clinical outcomes in these aggressive tumours. Clinical trials with immunotherapy or targeted therapy in patients with high-risk, advanced or metastatic disease are highly needed.

Treatment of symptomatic postoperative pelvic lymphoceles: A systematic review.

PURPOSE: A broad range of therapeutic options exists for symptomatic postoperative lymphoceles. However, no consensus exists on what is the optimal therapy. In this study, we aimed to compare the efficacy of currently available radiologic interventions in terms of number of successful interventions, number of recurrences, and number of complications. METHODS: A systematic review was conducted with a pre-defined search strategy for PubMed, EMBASE, and Cochrane databases from inception until September 2019. Quality assessment was performed using the 'Risk Of Bias In Non-randomized Studies - of Interventions' tool. Statistical heterogeneity was assessed using the I2 and χ2 test and a meta-analysis was considered for studies reporting on multiple interventions. RESULTS: 37 eligible studies including 732 lymphoceles were identified. Proportions of successful interventions for percutaneous fine needle aspiration, percutaneous catheter drainage, percutaneous catheter drainage with delayed or instantaneous addition of sclerotherapy, and embolization were as follows: 0.341 (95% confidence interval [CI]: 0.185-0.542), 0.612 (95% CI: 0.490-0.722), 0.890 (95% CI: 0.781-0.948), 0.872 (95% CI: 0.710-0.949), 0.922 (95% CI: 0.731-0.981). Random-effects meta-analysis of seven studies revealed a pooled relative risk for percutaneous catheter drainage with delayed addition of sclerotherapy of 1.57 (95% CI: 1.17-2.10) when compared to percutaneous catheter drainage alone. The risk of bias in this study was severe. CONCLUSIONS: This systematic review demonstrates that the success rates of percutaneous catheter drainage with sclerotherapy are more favorable when compared to percutaneous catheter drainage alone in the treatment of postoperative pelvic lymphoceles. Overall, percutaneous catheter drainage with delayed addition of sclerotherapy, and embolization showed the best outcomes.

Analysis of isolated loco-regional recurrence rate in intermediate risk early cervical cancer after a type C2 radical hysterectomy without adjuvant radiotherapy.

BACKGROUND: The efficacy of adjuvant radiotherapy in patients with intermediate risk early cervical cancer after radical hysterectomy is still under debate. Most guidelines recommend adjuvant radiotherapy, whereas others consider observation a viable option. OBJECTIVE: To investigate if patients with intermediate risk factors for cervical cancer who underwent radical hysterectomy may benefit from adjuvant radiotherapy. METHODS: Consecutive patients with tumor confined to the cervix and intermediate risk factors (according to Sedlis), treated between January 1982 and December 2014 who were observed after a type C2 radical hysterectomy formed the basis for this study. The frequency of recurrences, specifically isolated loco-regional recurrences, and the risk of death from recurrences, were analyzed. Data were analyzed using SPSS, version 23.0 for Windows RESULTS: A total of 161 patients were included in the analysis. Median age was 40 (range 20-76). Stages IB1 and IB2 were seen in 87 (54%) and 74 patients (46%), respectively. Squamous cell and non-squamous histology was seen in 114 (70.8%) and 47 patients (29.2%), respectively. Of the 161 patients, 25 (15.5%) had recurrent disease, of whom nine had an isolated loco-regional recurrence (5.6%). Median time to recurrence for isolated loco-regional recurrences was 28 months (range 9-151). Treatment for an isolated loco-regional recurrence was radiotherapy (n = 4) and chemoradiotherapy (n = 5). Four patients (2.5%) died from disease as a result of an isolated loco-regional recurrence. Actuarial disease- specific survival was 93.0% for the total group. No variables were found that predicted an isolated loco-regional recurrence. DISCUSSION: The mortality from isolated loco-regional recurrence in patients with intermediate risk factors for cervical cancer who underwent only radical hysterectomy type C2 was 2.5%. Further studies should compare outcomes between patients who undergo a type C2 radical hysterectomy without adjuvant radiotherapy with those undergoing a less radical hysterectomy but with adjuvant radiotherapy.

Essentials in cardiac arrest during cesarean section.

Cardiac arrest during cesarean section is very rare. Obstetrical teams have low exposure to these critical situations necessitating frequent rehearsal and knowledge of its differential diagnosis and treatment. A 40-year-old woman pregnant with triplets underwent cesarean sections because of vaginal bleeding due to a placenta previa at 35.2 weeks of gestation. Spinal anesthesia was performed. Asystole occurred during uterotomy. Immediate resuscitation and delivery of the neonates eventually resulted in good maternal and neonatal outcomes. The differential diagnosis is essential and should include obstetric and non-obstetric causes. We describe the consideration of Bezold Jarisch reflex and amniotic fluid embolism as most appropriate in this case.

[A woman with an abdominal mass]. / Een vrouw met een zwelling in de buik.

A 46-year-old woman presenting with gastroesophageal reflux complaints, unresponsive to treatment, was found to have a large lower abdominal mass during physical examination. CT-scanning revealed multiple fatty deposits under the right hemidiaphragm, besides the heterogenic lower abdominal mass. The mass and most of the deposits were removed surgically. Histological examination confirmed the diagnosis of a ruptured mature cystic teratoma with intraperitoneal deposits.