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Objective: Presence of lung metastases in low-risk gestational trophoblastic neoplasia (GTN) is generally considered not to influence prognosis. However, in a recent study in the Netherlands, GTN patients with lung metastases had a higher recurrence rate and more disease-specific deaths compared with patients without metastases. The aim of the present study was to validate these findings in a different country.Design: Historical cohort study.Setting: Charing Cross Hospital, United Kingdom.Population: A total of 1040 low-risk GTN patients treated with methotrexate (MTX) between 2002 and 2016 were identified: 65 with lung metastases (group 1) and 975 without metastases (group 2).Methods: Baseline characteristics, MTX resistance, survival and recurrence rates were recorded and compared between both groups.Main Outcome Measures: MTX resistance, recurrence rate and survival.Results: The occurrence of MTX resistance and median number of MTX courses to achieve remission was significantly higher in patients with lung metastases than patients without metastases (60% versus 38.9%, P = 0.001; and nine versus six courses, P < 0.001). All choriocarcinoma patients (n = 4) with lung metastases developed MTX resistance. The recurrence rate was also higher in group I (9.2% versus 2.7%; P = 0.012). Disease-specific survival was 100% in both groups.Conclusions: The presence of lung metastases at the start of MTX therapy is associated with increased incidence of MTX resistance and recurrence in low-risk GTN without affecting overall survival, which remains 100%. However, individuals with low-risk choriocarcinoma with lung metastases are likely to become resistant to MTX and primary multi-agent chemotherapy should be considered.Tweetable Abstract: The presence of lung metastases appears to increase the risk of recurrence in low-risk GTN, but does not affect overall cure rates and survival. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether gestational trophoblastic neoplasia (GTN) patients with lung metastases have more adverse outcomes such as resistance to chemotherapy, recurrence or death of disease compared with patients without lung metastases.Design: Historical observational cohort study.Setting: The Netherlands.Population: We identified 434 GTN patients (72 patients with lung metastases, 362 patients without metastases) between 1990 and 2012 registered in the Dutch national databases.Methods: Baseline characteristics, recurrence rates, Methotrexate (MTX) remission rates and deaths from disease were compared between patients with lung metastases (group I) and without lung metastases (group II) using the Fisher exact test or Mann-Whitney U-test where applicable.Main Outcome Measures: Methotrexate resistance, recurrences and survival.Results: Methotrexate resistance did not differ between group I and group II (62.9 versus 72.7% P = 0.19). However, the observed recurrence rate was significantly increased in patients with lung metastases compared with patients without metastases (16.7 versus 2.2% P < 0.0001), also after correction for antecedent pregnancy and interval (from the end of the antecedent pregnancy until the start of treatment). Disease-specific survival was 91.7% in the group with lung metastases and 100% in the patients without metastases (P < 0.0001).Conclusions: Although lung metastases are considered to be associated with a low risk of adverse outcomes, their presence appears to increase the risk for recurrence and death of disease. Further research is needed to evaluate whether the presence of lung metastases is an independent risk factor that needs adjustment in the FIGO scoring system and clinical classification system.Tweetable Abstract: In gestational trophoblastic neoplasia (GTN) recurrence is more often observed in the case of lung metastases. [ABSTRACT FROM AUTHOR]

Background: Gestational trophoblastic disease (GTD) is a rare pregnancy-related condition consisting of premalignant and malignant forms arising from proliferation of trophoblastic cells. The malignant forms are collectively referred to as gestational trophoblastic neoplasia (GTN) and are highly sensitive to chemotherapy. However, surgical procedures remain indispensable in the diagnosis and treatment of GTD., Objectives: The aim of this review was to summarize surgical interventions in the treatment of GTD and GTN. We reviewed indications, efficacy, possible complications, and oncological outcomes of surgery., Methods: Three searches were performed in the databases of PubMed, Embase, and the Cochrane Library to create an up-to-date overview of existing literature on the following subjects: (1) the role of primary hysterectomy in GTD and GTN; (2) the role of second curettage in GTD and GTN; (3) fertility sparing surgery in GTN; (4) surgical management of metastases. Included articles originated from the time period 1952-2022. Articles written in English, Spanish, and French were included., Outcomes: Thirty-eight articles were found and selected. Surgical evacuation through suction curettage is most used and advised in the treatment of GTD. A second curettage could be beneficial in patients with low hCG levels and low FIGO scores. In women who have completed their families, primary hysterectomy might be considered as the risk of subsequent GTN is lower than after suction curettage. In case of the rare forms of GTN (epithelioid trophoblastic tumor or placental site trophoblastic tumor) surgical tumor resection remains the most important step in treatment. Data on fertility sparing surgery in GTN are scarce and this treatment should be considered experimental., Conclusion and Outlook: Surgery remains an important part of treatment of GTD and is sometimes indispensable to achieve curation. Further collection of evidence is needed to determine treatment steps., (© 2023 S. Karger AG, Basel.)

Background: Ninety percent of cervical cancer (CC) diagnoses and deaths occur in low and middle-income countries (LMICs). Especially in these countries, where human and material resources are limited, there is a need for real-time screening methods that enable immediate treatment decisions (i.e., 'see and treat')., Objective: To evaluate whether handheld vital microscopy (HVM) enables real-time detection of microvascular alterations associated with cervical intraepithelial neoplasia (CIN) and CC., Methods: A cross-sectional study was conducted in an oncologic hospital and outpatient clinic, and included ten healthy controls, ten women with CIN, and ten women with CC. The microvasculature was assessed in four quadrants of the uterine cervix using HVM. The primary outcome was the presence of abnormal angioarchitecture (AA). Secondary outcomes included capillary loop density (CD), total vessel density (TVD), functional capillary density (FCD), and the proportion of perfused vessels (PPV)., Results: 198 image sequences of the cervical microvasculature were recorded. Compared to healthy controls, significantly more abnormal image sequences were observed in women with high-grade CIN (11 % vs. 44 %, P < 0.001) and women with CC (11 % vs. 69 %, P < 0.001). TVD, FCD, and PPV were lower in women with CIN and CC., Conclusions: HVM enables easy, real-time, non-invasive assessment of cervical lesions through the detection of microvascular alterations. Thereby, HVM potentially provides an opportunity for point-of-care screening, which may enable immediate treatment decisions (see and treat) and reduce the number of unnecessary surgical interventions., Competing Interests: Declaration of competing interest Braedius Medical, a company owned by a relative of Dr. Ince, has developed CytoCam-IDF imaging used in this study. Dr. Ince has no financial relationship with Braedius Medical of any sort, i.e., never owned shares or received consultancy or speaker fees from Braedius Medical. Dr. Ince is CSO of Active Medical BV, Leiden, The Netherlands, a company that provides devices (OxyCam), software (MicroTools), education (Microcirculation Academy), and services related to clinical microcirculation. All other authors declare that they have no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To develop a color code and to investigate the validity of Laser Speckle Contrast Imaging (LSCI) for measuring burn wound healing potential (HP) in burn patients as compared to the reference standard Laser Doppler Imaging (LDI)., Method: A prospective, observational, cohort study was conducted in adult patients with acute burn wounds. The relationship between mean flux measured with LDI and mean perfusion units (PU) measured with LSCI was expressed in a regression formula. Measurements were performed between 2 and 5 days after the burn wound. The creation of a LSCI color code was done by mapping the clinically validated color code of the LDI to the corresponding values on the LSCI scale. To assess validity of the LSCI, the ability of the LSCI to discriminate between HP < 14 and ≥ 14 days and HP < 21 and original ≥ 21 days according to the LDI reference standard was evaluated, with calculation of receiver operating characteristics (ROC) curves., Results: A total of 50 patients were included with a median age of 40 years and total body surface area burned of 6%. LSCI values of 143 PU and 113 PU were derived as the cut-off values for the need of conservative treatment (HP < 14 and ≥ 14 days) resp. surgical closure (HP < 21 and ≥ 21 days). These LSCI cut off values showed a good discrimination between HP 14 days versus ≥ 14 days (Area Under Curve (AUC)= 0.89; sensitivity 85% and specificity = 82%) and a good discrimination between HP 21 days versus ≥ 21 days (AUC of 0.89, sensitivity 81% and specificity 88%)., Conclusion: This is the first study in which a color code for the LSCI in adult clinical burn patients has been developed. Our study reconfirms the good performance of the LSCI for prediction of burn wound healing potential. This provides additional evidence for the potential value of the LSCI in specialized burn care., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest. Perimed AB provided the Laser Speckle Contrast Imager for free. Perimed AB did not have any involvement in the study design, data collection and data analysis, nor in the writing process and submission of this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Objective: To evaluate outcomes of European cross-border multidisciplinary tumor boards in terms of participation, adherence to treatment recommendations, and access to novel treatment strategies., Methods: The European reference network for rare gynecological tumors (EURACAN G2 domain) aims to improve the diagnosis, management, and treatment of patients with these cancers. Cross-border multidisciplinary tumor boards were initiated to facilitate intercollegiate clinical discussions across Europe and increase patients' access to specialist treatment recommendations and clinical trials. All G2 healthcare providers were invited to participate in monthly multidisciplinary meetings. Patient data were collected using a standardized form and case summaries were distributed before each meeting. After each tumor board, a meeting summary with treatment recommendations was sent to all participants and the project manager at the coordinating center. The multidisciplinary tumor board format and outcomes were regularly discussed at G2 domain meetings. Anonymized clinical data and treatment recommendations were registered in a prospective database. For this report, clinical data were collected between November 2017 and December 2020 and follow-up data retrieved until May 2021., Results: During the 3-year period, 31 multidisciplinary tumor boards were held with participants from 10 countries and 20 centers. 91 individual patients were discussed between one and six times for a total of 109 case discussions. Follow-up data were retrieved from 64 patients and 80 case discussions. Adherence to treatment recommendations was 99%. Multidisciplinary tumor board recommendations resulted in 11 patients getting access to off-label treatment and one patient being enrolled in a clinical trial in another European country. 14/91 patients were recommended for surveillance only when additional treatment had been considered locally., Conclusion: Cross-border multidisciplinary tumor boards enable networking and clinical collaboration between healthcare professionals in different countries. Surveillance strategies, off-label drug use, and increased participation in clinical trials are possible benefits to patients with rare gynecological tumors., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2023. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Background:  Pediatric burns significantly impact the short-term health-related quality of life (HRQL) of children. Knowledge regarding the long-term impact is scarce. We therefore evaluated the parent-reported HRQL in pediatric burn patients 5 to 7 years after burns., Methods:  We invited parents of eligible children admitted to a Dutch Burn Center between August 2011 and September 2012. This sample was enriched with children with severe burns (> 10% of total body surface area [TBSA] burned) admitted between January 2010 and March 2013. The EQ-5D was completed by parents 5 to 7 years postburn. Outcomes and predictive factors were studied and compared between children with minor/moderate and severe burns., Results:  We included 130 children (mean TBSA burned 7%): 102 children with mild/intermediate burns and 28 with severe burns. Mean EQ-5D summary was 0.96 and EQ visual analogue scale (VAS) 93.1. These outcomes were significantly better in children with minor/moderate burns (0.97; 94.4) compared with children with severe burns (0.93; 88.3) ( p  < 0.05). Nineteen percent of the children with minor/moderate burns and 43% of those with severe burns reported any problems. The most frequently reported problem was anxiety/depression for both groups. Pain/discomfort ( p  = 0.012) and cognition ( p  = 0.035) were statistically significantly worse in children with severe burns compared with those with minor/moderate burns. Full thickness burns and number of surgeries were found to predict long-term HRQL impairment., Conclusion:  Five to seven years postburn, the majority of children in our study (76%) did not experience long-term problems with HRQL. In a minority of the children, burns showed to have a prolonged negative impact, especially in those being severely burned and who had to undergo surgery for their burns. Most experienced problems were related to anxiety/depression. These important insights could be used to inform children and their parents about the expected long-term HRQL after pediatric burns., Competing Interests: None declared., (Thieme. All rights reserved.)

Purpose: It is unknown if future fertility is compromised by the administration of chemotherapy during pregnancy. The aim of this study was to identify if chemotherapy affects the maternal ovaries during pregnancy and whether these effects depend on type of chemotherapy and duration of exposure., Methods: Pregnant 8-week-old female BL6 mice were exposed to 6 different single chemotherapeutic agents (carboplatin, cisplatin, paclitaxel, epirubicin, doxorubicin, or cyclophosphamide) or saline at gestational day (GD) 13.5. The mice were sacrificed at GD 15.5 or GD 18.5. Ovaries were assessed by histopathology and immunohistochemistry. Follicle count was determined per follicle stage and per treatment modality., Results: Maternal ovarian damage was demonstrated by the presence of apoptosis and necrosis in preantral follicles. The extent of this damage depends upon type of chemotherapy and duration of exposure (2 or 5 days). After short exposure, 81% of ovaries showed histopathologic signs of damage compared to 36% after long exposure, which might suggest a transient effect. Loss of primordial follicles (PMFs) was observed after both short and long exposure, with a reduction of more than 70%. Evidence of DNA damage, as demonstrated by phospho-H2AX expression, was present in 23% (range 0-89%) of PMFs exposed to chemotherapy, but only in the short exposure group. Overall, the least damage was seen after administration of paclitaxel., Conclusion: Despite physiological ovarian function suppression during gestation, chemotherapy-induced damage of the ovaries occurs in pregnant mouse models, potentially affecting future fertility., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Laser-based tissue perfusion monitoring techniques have been increasingly used in animal and human research to assess blood flow. However, these techniques use arbitrary units, and knowledge about their comparability is scarce. This study aimed to model the relationship between laser speckle contrast imaging (LSCI) and laser Doppler perfusion imaging (LDPI), for measuring tissue perfusion over a wide range of blood flux values., Methods: Fifteen healthy volunteers (53% female, median age 29 [IQR 22-40] years) were enrolled in this study. We performed iontophoresis with sodium nitroprusside on the forearm to induce regional vasodilation to increase skin blood flux. Besides, a stepwise vascular occlusion was applied on the contralateral upper arm to reduce blood flux. Both techniques were compared using a linear mixed model analysis., Results: Baseline blood flux values measured by LSCI were 33 ± 6.5 arbitrary unit (AU) (Coefficient of variation [CV] = 20%) and by LDPI 60 ± 11.5 AU (CV = 19%). At the end of the iontophoresis protocol, the regional blood flux increased to 724 ± 412% and 259 ± 87% of baseline measured by LDPI and LSCI, respectively. On the other hand, during the stepwise vascular occlusion test, the blood flux reduced to 212 ± 40% and 412 ± 177% of its baseline at LDPI and LSCI, respectively. A strong correlation was found between the LSCI and LDPI instruments at increased blood flux with respect to baseline skin blood flux; however, the correlation was weak at reduced blood flux with respect to baseline., Discussion: LSCI and LDPI instruments are highly linear for blood flux higher than baseline skin blood flux; however, the correlation decreased for blood flux lower than baseline. This study's findings could be a basis for using LSCI in specific patient populations, such as burn care., (© 2022 The Authors. Microcirculation published by John Wiley & Sons Ltd.)

Purpose: Cervical screening can prevent cancer by detection and treatment of cervical intraepithelial neoplasia grade 2 or 3 (CIN2/3). Screening also results in considerable overtreatment because many CIN2/3 lesions show spontaneous regression when left untreated. In this multicenter longitudinal cohort study of women with untreated CIN2/3, the prognostic value of FAM19A4/miR124-2 methylation was evaluated for clinical regression., Patients and Methods: Women with CIN2/3 were prospectively followed for 24 months. Surgical excision was replaced by a wait-and-see policy. FAM19A4/miR124-2 methylation was evaluated on all clinician-collected samples and self-collected samples collected at baseline. Every 6 months, human papillomavirus (HPV) testing and cytology were conducted on a clinician-collected sample, and a colposcopic examination was performed by a gynecologist to exclude progression. At the final study visit, two biopsies were taken. Clinical regression was defined as histologically confirmed absence of CIN2+ or an HPV-negative clinician-collected sample with normal cytology. Regression incidences were estimated using the Kaplan-Meier method., Results: One hundred fourteen women (median age, 30 years; range, 20-53 years) were included, 80 of whom were diagnosed with CIN2 and 34 with CIN3. During the study, 65.8% of women (75/114) did not receive surgical treatment. Women with a negative FAM19A4/miR124-2 result on the baseline clinician-collected sample showed more clinical regression (74.7%) than women with a positive methylation result (51.4%, P = .013). Regression in women with a negative FAM19A4/miR124-2 methylation test was highest when cytology was atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion (88.4%) or HPV16 was negative (85.1%)., Conclusion: Most women with untreated CIN2/3 and a negative baseline FAM19A4/miR124-2 methylation test showed clinical regression. Methylation, in combination with cytology or HPV genotyping, can be used to support a wait-and-see policy in women with CIN2/3.

Objective: Treatment strategies for bulky lymph nodes in patients with locally advanced cervical cancer scheduled for definitive chemoradiation include nodal boosting with radiotherapy, surgical debulking, or both. The aim of this retrospective cohort study was to compare survival and toxicity in patients receiving these treatments and to compare them with a group that received neither form of treatment., Methods: Women diagnosed between January 2009 and January 2017 with International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IB2, IIA2-IVA cervical cancer with lymph nodes ≥1.5 cm without upper limit on pretreatment imaging and treated with definitive chemoradiation were selected from the Netherlands Cancer Registry. Patients were categorized by intention-to-treat strategy: boosting, debulking, or neither treatment, with subgroup analysis for patients receiving both treatments, that is, debulking with boosting. Overall and relapse-free survival outcomes were compared by Kaplan-Meier and Cox regression analyses and toxicity by logistic regression analysis., Results: Of 190 patients, 101 (53%) received only nodal boosting, 31 (16%) debulking alone, 29 (15%) debulking combined with boosting, and 29 (15%) received neither treatment. The 5 year overall and relapse-free survival for the treatment groups were 58%, 45% and 45% (p=0.19), and 47%, 44% and 46% (p=0.87), respectively. Multivariable Cox regression analyses demonstrated no differences in overall and relapse-free survival. Combination of debulking with boosting was associated with decreased overall and relapse-free survival compared with debulking alone (HR 2.47, 95% CI 1.22 to 5.00; and HR 2.37, 95% CI 1.14 to 4.93). Nodal boosting was independently associated with a decreased toxicity risk compared with debulking strategy (OR 0.37, 95% CI 0.16 to 0.83)., Conclusions: This study showed no survival benefit from either nodal boosting or debulking strategy in patients with suspicious bulky nodes. Nodal boosting might, however, be associated with less toxicity. Dual treatment with debulking and boosting showed a worse survival outcome because this group probably represents patients with poor prognostic factors., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2022. Re-use permitted under CC BY. Published by BMJ.)

Background: Risk factors and mechanisms of injury may change over time. Since knowledge on aetiology of severe burn incidents in children under 5 years of age in the Netherlands is outdated, this study aimed to identify current risk factors and mechanisms of severe burn injury in children under 5 years of age in the Netherlands to direct future prevention campaigns., Methods: Information on personal-, environmental- and behavioural circumstances as well as the mechanism of burn injury was prospectively collected in all burn centres during one year from patient records and structured interviews with parents., Results: Boys around 18 months of age, who, while in upright position, pulled down a cup of hot tea over themselves, were overrepresented. Children in families with more children, having a migration background, living in urbanised neighborhoods or with a low socioeconomic status (SES) are at increased risk for severe burn injury. Most incidents happened in their own home with the parents in close proximity to the child., Conclusion: Outcomes of this prospective cohort study provide up-to-date and extensive knowledge on the aetiology of severe burn incidents in children under 5 years of age in the Netherlands, and provide directions for prevention policy and campaigns., (Copyright © 2021 Elsevier Ltd and ISBI. All rights reserved.)

Background: It is unknown whether lung-protective ventilation is applied in burn patients and whether they benefit from it. This study aimed to determine ventilation practices in burn intensive care units (ICUs) and investigate the association between lung-protective ventilation and the number of ventilator-free days and alive at day 28 (VFD-28)., Methods: This is an international prospective observational cohort study including adult burn patients requiring mechanical ventilation. Low tidal volume ( V T ) was defined as V T  ≤ 8 mL/kg predicted body weight (PBW). Levels of positive end-expiratory pressure (PEEP) and maximum airway pressures were collected. The association between V T and VFD-28 was analyzed using a competing risk model. Ventilation settings were presented for all patients, focusing on the first day of ventilation. We also compared ventilation settings between patients with and without inhalation trauma., Results: A total of 160 patients from 28 ICUs in 16 countries were included. Low V T was used in 74% of patients, median V T size was 7.3 [interquartile range (IQR) 6.2-8.3] mL/kg PBW and did not differ between patients with and without inhalation trauma ( p  = 0.58). Median VFD-28 was 17 (IQR 0-26), without a difference between ventilation with low or high V T ( p  = 0.98). All patients were ventilated with PEEP levels ≥5 cmH 2 O; 80% of patients had maximum airway pressures <30 cmH 2 O., Conclusion: In this international cohort study we found that lung-protective ventilation is used in the majority of burn patients, irrespective of the presence of inhalation trauma. Use of low V T was not associated with a reduction in VFD-28., Trial Registration: Clinicaltrials.gov NCT02312869. Date of registration: 9 December 2014., (© The Author(s) 2021. Published by Oxford University Press.)

Background: Clinicians are unable to provide individualized counseling regarding risk of progression for patients with a complete hydatidiform mole (CHM). We developed nomograms enabling early prediction of post-molar gestational trophoblastic neoplasia (GTN) and resistance to methotrexate (MTX) based on a single serum human chorion gonadotropin (hCG) measurement., Methods: We generated two nomograms with logistic regression: to predict post-molar GTN, and MTX resistance. For patients with high probability to progress to post-molar GTN or MTX resistance, we determined hCG cut-offs at 97.5% specificity to select patients for additional- or adjustments in current treatment., Results: The nomograms had a good to excellent ability to distinguish either between patients with uneventful hCG regression versus progression to post molar GTN, or between patients cured by MTX versus patients in whom resistance would occur. At 97.5% specificity, we identified 66% (95%CI 56-75) of the 149 patients who would progress to post-molar GTN, four weeks after initial curettage. For patients treated with MTX, we identified 55% (95%CI 23-83) of the 43 patients who would become resistant, preceding their third course at 97.5% specificity., Conclusion: The nomograms and cut-off levels can be used to assist in counseling for patients diagnosed with CHM., Competing Interests: Declaration of Competing Interest The authors have nothing to disclose., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: Gestational trophoblastic disease (GTD) is a group of heterogeneous disorders characterized by abnormal proliferation of trophoblastic tissue. GTD is a rare disease that is curable in the vast majority of patients when managed appropriately. The aim of the review is to discuss the important steps necessary to establish a center of excellence for GTD., Recent Findings: Care of patients with a rare disease is complicated by lack of strong evidence, scattering of patients across the country and limited expertise of medical professionals. The establishment of a center of excellence requires awareness of its benefit, funding, a solid business case and most of all dedicated clinicians. A multidisciplinary team and formulation of national guidelines are important steps before clinical pathways can be developed and treatment can be evaluated for improvement of care and research purposes. International embedding can facilitate the process and lead to the development of a (inter) national acknowledged sustainable center of excellence., Summary: Centers of excellence could optimize the care of patients with GTD and promote research., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)