Asymptomatic lipofibroadenoma in a 17-year-old male:a case report and literature review of a rare entity

Background: The most common thymic tumours, thymomas, are derived from thymic epithelium and are generally low-grade neoplasm. Frankly malignant tumours, thymic carcinomas are rarer still. Exceedingly rare thymic tumours contain a mesenchymal tissue component such as fibrous connective tissue and/or mature fat. Lipofibroadenoma (LFA) is a very rare mixed epithelial-mesenchymal thymic tumour, included in the category of thymic epithelial tumors. LFA in addition to a mature adipocytic component, contains variable epithelial and mesenchymal tissue components. Owing to the presence of an epithelial component in LFA, this entity, in contrast to thymolipoma, is included in the World Health Organization (WHO) category of thymic epithelial neoplasm. Currently only 12 LFA cases have been described. The 12 previously reported cases all behaved in a benign fashion, although four cases were associated with a conventional type of thymoma. We here present a new, 13th, case of LFA. Case Description: The LFA was discovered incidentally in a previously healthy 17-year-old male after investigations for suspected pneumonia. On imaging a mass was discovered in the anterior mediastinum which was subsequently surgically removed. The resected tumour was extensively investigated, including the first instance of full molecular analysis of this rare entity and all available literature on LFA was sourced to provide a comprehensive overview. The histology of this LFA was similar to previously described cases. No gene mutations or rearrangements were identified. The patient made an uneventful recovery and after 13 months of follow-up remained well. Conclusions: An additional, 13th case of LFA is presented. Based on the available literature it appears that LFA may be considered a benign composite thymic tumour, although the combination of an additional conventional thymoma component may warrant closer follow-up.</p

Multi-modal 3-Dimensional Visualization of Pediatric Neuroblastoma:Aiding Surgical Planning Beyond Anatomical Information

Background: Patient-specific 3D models of neuroblastoma and relevant anatomy are useful tools for surgical planning. However, these models do not represent the heterogenous biology of neuroblastoma. This heterogeneity is visualized with the ADC and 123I-MIGB-SPECT-CT imaging. Combining these multi-modal data into preoperative 3D heatmaps, may allow differentiation of the areas of vital and non-vital tumor tissue. We developed a workflow to create multi-modal preoperative 3D models for neuroblastoma surgery. Methods: We included 7 patients who underwent neuroblastoma surgery between 2022 and 2023. We developed 3D models based on the contrast enhanced T1-weighted MRI scans. Subsequently, we aligned the corresponding ADC and 123I-MIBG-SPECT-CT images using rigid transformation. We estimated registration precision using the Dice score and the target registration error (TRE). 3D heatmaps were computed based on ADC and 123I-MIBG uptake. Results: The registration algorithm had a median Dice score of 0.81 (0.75–0.90) for ADC and 0.77 (0.65–0.91) for 123I-MIBG-SPECT. For the ADC registration, the median TRE of renal vessels was 4.90 mm (0.86–10.18) and of the aorta 4.67 mm (1.59–12.20). For the 123I -MIBG-SPECT imaging the TRE of the renal vessels was 5.52 mm (1.71–10.97) and 5.28 mm (3.33–16.77) for the aorta. Conclusions: We successfully developed a registration workflow to create multi-modal 3D models which allows the surgeon to visualize the tumor and its biological behavior in relation to the surrounding tissue. Future research will include linking of pathological results to imaging data, to validate these multi-modal 3D models. Level of Evidence: Level IV. Type of Study: Clinical Research.</p

Virtual Resection: A New Tool for Preparing for Nephron-Sparing Surgery in Wilms Tumor Patients

Nephron-sparing surgery (NSS) in Wilms tumor (WT) patients is a surgically challenging procedure used in highly selective cases only. Virtual resections can be used for preoperative planning of NSS to estimate the remnant renal volume (RRV) and to virtually mimic radical tumor resection. In this single-center evaluation study, virtual resection for NSS planning and the user experience were evaluated. Virtual resection was performed in nine WT patient cases by two pediatric surgeons and one pediatric urologist. Pre- and postoperative MRI scans were used for 3D visualization. The virtual RRV was acquired after performing virtual resection and a questionnaire was used to assess the ease of use. The actual RRV was derived from the postoperative 3D visualization and compared with the derived virtual RRV. Virtual resection resulted in virtual RRVs that matched nearly perfectly with the actual RRVs. According to the questionnaire, virtual resection appeared to be straightforward and was not considered to be difficult. This study demonstrated the potential of virtual resection as a new planning tool to estimate the RRV after NSS in WT patients. Future research should further evaluate the clinical relevance of virtual resection by relating it to surgical outcome

Asymptomatic lipofibroadenoma in a 17-year-old male: a case report and literature review of a rare entity

BACKGROUND: The most common thymic tumours, thymomas, are derived from thymic epithelium and are generally low-grade neoplasm. Frankly malignant tumours, thymic carcinomas are rarer still. Exceedingly rare thymic tumours contain a mesenchymal tissue component such as fibrous connective tissue and/or mature fat. Lipofibroadenoma (LFA) is a very rare mixed epithelial-mesenchymal thymic tumour, included in the category of thymic epithelial tumors. LFA in addition to a mature adipocytic component, contains variable epithelial and mesenchymal tissue components. Owing to the presence of an epithelial component in LFA, this entity, in contrast to thymolipoma, is included in the World Health Organization (WHO) category of thymic epithelial neoplasm. Currently only 12 LFA cases have been described. The 12 previously reported cases all behaved in a benign fashion, although four cases were associated with a conventional type of thymoma. We here present a new, 13th, case of LFA. CASE DESCRIPTION: The LFA was discovered incidentally in a previously healthy 17-year-old male after investigations for suspected pneumonia. On imaging a mass was discovered in the anterior mediastinum which was subsequently surgically removed. The resected tumour was extensively investigated, including the first instance of full molecular analysis of this rare entity and all available literature on LFA was sourced to provide a comprehensive overview. The histology of this LFA was similar to previously described cases. No gene mutations or rearrangements were identified. The patient made an uneventful recovery and after 13 months of follow-up remained well. CONCLUSIONS: An additional, 13th case of LFA is presented. Based on the available literature it appears that LFA may be considered a benign composite thymic tumour, although the combination of an additional conventional thymoma component may warrant closer follow-up

Uterine bathing with sonography gel prior to IVF/ICSI-treatment in patients with endometriosis, a multicentre randomised controlled trial

STUDY QUESTION What is the effect of uterine bathing with sonography gel prior to IVF/ICSI-treatment on live birth rates after fresh embryo transfer in patients with endometriosis? SUMMARY ANSWER After formal interim analysis and premature ending of the trial, no significant difference between uterine bathing using a pharmacologically neutral sonography gel compared to a sham procedure on live birth rate after fresh embryo transfer in endometriosis patients (26.7% vs. 15.4%, relative risk (RR) 1.73, 95% confidence interval (CI) 0.81–3.72; P-value 0.147) could be found, although the trial was underpowered to draw definite conclusions. WHAT IS KNOWN ALREADY Impaired implantation receptivity contributes to reduced clinical pregnancy rates after IVF/ICSI-treatment in endometriosis patients. Previous studies have suggested a favourable effect of tubal flushing with Lipiodol® on natural conceptions. This benefit might also be explained by enhancing implantation through endometrial immunomodulation. Although recent studies showed no beneficial effect of endometrial scratching, the effect of mechanical stress by intrauterine infusion on the endometrium in endometriosis patients undergoing IVF/ICSI-treatment has not been investigated yet. STUDY DESIGN, SIZE, DURATION We performed a multicentre, patient-blinded, randomised controlled trial in which women were randomly allocated to either a Gel Infusion Sonography (GIS, intervention group) or a sham procedure (control group) prior to IVF/ICSI-treatment. Since recruitment was slow and completion of the study was considered unfeasible, the study was halted after inclusion of 112 of the planned 184 women. PARTICIPANTS/MATERIALS, SETTING, METHODS We included infertile women with surgically confirmed endometriosis ASRM stage I–IV undergoing IVF/ICSI-treatment. After informed consent, women were randomised to GIS with intrauterine instillation of ExEm-gel® or sonography with gel into the vagina (sham). This was performed in the cycle preceding the embryo transfer, on the day GnRH analogue treatment was started. The primary endpoint was live birth rate after fresh embryo transfer. Analysis was performed by both intention-to-treat and per-protocol. MAIN RESULTS AND THE ROLE OF CHANCE Between July 2014 to September 2018, we randomly allocated 112 women to GIS (n = 60) or sham procedure (n = 52). The live birth rate after fresh embryo transfer was 16/60 (26.7%) after GIS versus 8/52 (15.4%) after the sham (RR 1.73, 95% CI 0.81–3.72; P-value 0.147). Ongoing pregnancy rate was 16/60 (26.7%) after GIS versus 9/52 (17.3%) in the controls (RR 1.54, 95% CI 0.74–3.18). Miscarriage occurred in 1/60 (1.7%) after GIS versus 5/52 (9.6%) in the controls (RR 0.17, 95% CI 0.02–1.44) women. Uterine bathing resulted in a higher pain score compared with a sham procedure (visual analogue scale score 2.7 [1.3–3.5] vs. 1.0 [0.0–2.0], P < 0.001). There were two adverse events after GIS compared with none after sham procedures. LIMITATIONS, REASONS FOR CAUTION The study was terminated prematurely due to slow recruitment and trial fatigue. Therefore, the trial is underpowered to draw definite conclusions regarding the effect of uterine bathing with sonography gel on live birth rate after fresh embryo transfer in endometriosis patients undergoing IVF/ICSI-treatment. WIDER IMPLICATIONS OF THE FINDINGS We could not demonstrate a favourable effect of uterine bathing procedures with sonography gel prior to IVF/ICSI-treatment in patients with endometriosis. STUDY FUNDING/COMPETING INTEREST(S) Investigator initiated study. IQ Medical Ventures provided the ExEm FOAM® kits free of charge, they were not involved in the study design, data management, statistical analyses and/or manuscript preparation, etc. C.B.L. reports receiving grants from Ferring, Merck and Guerbet, outside the submitted work. C.B.L. is Editor-in-Chief of Human Reproduction. V.M. reports grants and other from Guerbet, outside the submitted work. B.W.M. reports grants from NHMRC (GNT1176437), personal fees from ObsEva, Merck and Merck KGaA, Guerbet and iGenomix, outside the submitted work. N.P.J. reports research funding from Abb-Vie and Myovant Sciences and consultancy for Vifor Pharma, Guerbet, Myovant Sciences and Roche Diagnostics, outside the submitted work. K.D. reports personal fees from Guerbet, outside the submitted work. The other authors do not report any conflicts of interest. No financial support was provided. TRIAL REGISTRATION NUMBER NL4025 (NTR4198) TRIAL REGISTRATION DATE 7 October 2013 DATE OF FIRST PATIENT’S ENROLMENT 22 July 201

The contribution of surgical clips for optimizing highly-conformal image-guided flank irradiation in pediatric renal tumors: a single center experience

Background and aims: Two-opposing photon beams are considered standard of care for flank irradiation in pediatric patients with renal tumors. Nowadays, Image-Guided Radiotherapy (IGRT) techniques allow high-precision dose delivery to complex flank target volumes taking into account postoperative organ shifts and tumor bed motion. This study examines the contribution of a lateral and superior surgical clip on flank target volume delineation intended for IGRT. Methods: Between 01-2015 and 09-2019, 30/162 newly-diagnosed pediatric patients with renal tumors, lateral/superior surgical clips (n = 30/30) and available 4D-CT-scans (n = 27/30), underwent postoperative flank irradiation. The lateral and superior clip, as respective markers for the lateral tumor extension and intrafraction motion, were analyzed. The positive and negative values depict the lateral/dorsal/cranial or the medial/ventral/caudal direction, respectively. Planning target volumes (PTV) were generated based on lateral clips (PTV latclip), superior clips with 4D-CT technology (PTV supclip), and both clips combined (PTV combined), and compared to an approach without clips (PTV noclip). Results: Indicated by clips, the mean lateral tumor bed extension along the posterior wall was 74° (range: 50°–93°), while mean intrafraction motion was +1.2 mm (range: −1.8/+4.8 mm), +0.6 mm (range: +0.6/+4.9 mm), −0.3 mm (range: −3.8/+0.7 mm) in craniocaudal, ventrodorsal, mediolateral direction, respectively. The median PTV noclip (556 mL) was statistically different from the median PTV latclip (454 mL, p = <0.01), median PTV supclip (373 mL, p = <0.01) and median PTV combined (348 mL p = <0.01). Conclusion: In pediatric patients with renal tumors, surgical clips at the lateral and superior border of the tumor bed can optimize flank target volume delineation and, consequently, reduce the normal tissue volume receiving high-dose irradiation when IGRT techniques are applied

Diagnostic accuracy of image-guided core needle biopsy of non-central nervous system tumors in children

Background and aims: Core needle biopsies (CNB) are less invasive, cause less morbidity, and have lower costs than open biopsies (OB). However, the number of studies reporting CNB accuracy in pediatric tumors is limited and series are small. The aim of this study is to investigate if CNB diagnosis is concordant with the final diagnosis in pediatric solid non-central nervous system (CNS) tumors. Methods: Data from all patients treated in a single center between November 2014 and December 2019 were collected from the national pathology database and from local medical records. Data collection included age, sex, CNB diagnosis, final diagnosis, number of cores obtained, number of cores used for histology, cumulative core length, greatest dimension of the lesion, lesion volume, and complications. Results: Out of 361 CNB, 95.6% (345/361) provided a diagnosis. A resection or follow-up biopsy was performed in 201 cases. The final diagnosis was concordant with the CNB in 100% (201/201) of cases. The age, number of cores used for histology, and the greatest dimension of the lesion did not significantly differ between diagnostic and nondiagnostic CNB. The cumulative core length of diagnostic CNB was significantly higher than in the nondiagnostic group (24.72 mm vs. 13.37 mm, p-value.022). Complications occurred in 2.1% (7/337) of CNB procedures. Molecular analysis was successful in 228/233 (98%) of cases in which it was performed. Conclusions: CNB diagnosis is highly concordant with the final diagnosis and the diagnostic rate is high. The complication rate in CNB is low

Clinical Application and Further Development of Augmented Reality Guidance for the Surgical Localization of Pediatric Chest Wall Tumors

Background: Surgical treatment of pediatric chest wall tumors requires accurate surgical planning and tumor localization to achieve radical resections while sparing as much healthy tissue as possible. Augmented Reality (AR) could facilitate surgical decision making by improving anatomical understanding and intraoperative tumor localization. We present our clinical experience with the use of an AR system for intraoperative tumor localization during chest wall resections. Furthermore, we present the pre-clinical results of a new registration method to improve our conventional AR system. Methods: From January 2021, we used the HoloLens 2 for pre-incisional tumor localization during all chest wall resections inside our center. A patient-specific 3D model was projected onto the patient by use of a five-point registration method based on anatomical landmarks. Furthermore, we developed and pre-clinically tested a surface matching method to allow post-incisional AR guidance by performing registration on the exposed surface of the ribs. Results: Successful registration and holographic overlay were achieved in eight patients. The projection seemed most accurate when landmarks were positioned in a non-symmetric configuration in proximity to the tumor. Disagreements between the overlay and expected tumor location were mainly due to user-dependent registration errors. The pre-clinical tests of the surface matching method proved the feasibility of registration on the exposed ribs. Conclusions: Our results prove the applicability of AR guidance for the pre- and post-incisional localization of pediatric chest wall tumors during surgery. The system has the potential to enable intraoperative 3D visualization, hereby facilitating surgical planning and management of chest wall resections

Locoregional control using highly conformal flank target volumes and volumetric-modulated arc therapy in pediatric renal tumors: Results from the Dutch national cohort

Background and purpose: In pediatric renal tumors, conventional two opposing photon beams have been used to cover the postoperative flank target volume for decades. This single center study describes the locoregional outcome using highly conformal flank target volumes adjusted for postoperative changes and intra-fraction motion combined with Volumetric-Modulated Arc Therapy (VMAT). Materials and methods: Between 01-2015 and 12-2019, 36/161 newly diagnosed patients with renal tumors underwent flank only irradiation (n = 30) or flank + whole lung irradiation (n = 6) using highly conformal target volumes in line with the SIOP-RTSG consensus statement. VMAT consisted of full-arc 10MV photon beams optimized for constraints of the organs at risk. In case of locoregional relapses, image co-registration and dose reconstruction was performed. Each relapse was classified as either ‘infield’ (V95%relapse: ≥99.0%), ‘marginal’ (V95%relapse: 20.0–98.9%) or ‘outfield’ (V95%relapse: 0–19.9%). Results: At a median follow-up from diagnosis of 3.1 years (range:0.4–5.7), the estimated 2-year Locoregional Control Rate, Disease-Free Interval and Overall Survival were 94%, 91% and 94%, respectively. Locoregional relapse was observed in two patients. One patient had a combined tumor bed and regional recurrence, classified as infield (V95%relapse: 100%) and outfield (V95%relapse: 1.2%). The second patient had a regional relapse in the inferior vena cava classified as marginal recurrence (V95%relapse: 93%). Relapses would not have been adequately covered by conventional beams. Conclusions: This single center analysis provides encouraging evidence that excellent locoregional control can be obtained by using highly conformal flank target volumes with VMAT in pediatric renal tumors. The safety of this approach will be validated in a prospective multicenter study

A multi-centred randomised trial of radical surgery versus adjuvant chemoradiotherapy after local excision for early rectal cancer

Background: Rectal cancer surgery is accompanied with high morbidity and poor long term functional outcome. Screening programs have shown a shift towards more early staged cancers. Patients with early rectal cancer can potentially benefit significantly from rectal preserving therapy. For the earliest stage cancers, local excision is sufficient when the risk of lymph node disease and subsequent recurrence is below 5 %. However, the majority of early cancers are associated with an intermediate risk of lymph node involvement (5-20 %) suggesting that local excision alone is not sufficient, while completion radical surgery, which is currently standard of care, could be a substantial overtreatment for this group of patients. Methods/Study design: In this multicentre randomised trial, patients with an intermediate risk T1-2 rectal cancer, that has been locally excised using an endoluminal technique, will be randomized between adjuvant chemo-radiotherapylimited to the mesorectum and standard completion total mesorectal excision (TME). To strictly monitor the risk of locoregional recurrence in the experimental arm and enable early salvage surgery, there will be additional follow up with frequent MRI and endoscopy. The primary outcome of the study is three-year local recurrence rate. Secondary outcomes are morbidity, disease free and overall survival, stoma rate, functional outcomes, health related quality of life and costs. The design is a non inferiority study with a total sample size of 302 patients. Discussion: The results of the TESAR trial will potentially demonstrate that adjuvant chemoradiotherapy is an oncological safe treatment option in patients who are confronted with the difficult clinical dilemma of a radically removed intermediate risk early rectal cancer by polypectomy or transanal surgery that is conventionally treated with subsequent radical surgery. Preserving the rectum using adjuvant radiotherapy is expected to significantly improve morbidity, function and quality of life if compared to completion TME surgery. Trial registration:NCT02371304, registration date: February 2015