Unraveling the relations between post-traumatic stress symptoms, neurocognitive functioning, and limbic white matter in pediatric brain tumor patients.

Background: Pediatric brain tumor patients are at risk of developing neurocognitive impairments and associated white matter alterations. In other populations, post-traumatic stress symptoms (PTSS) impact cognition and white matter. This study aims to investigate the effect of PTSS on neurocognitive functioning and limbic white matter in pediatric brain tumor patients. Methods: Sixty-six patients (6-16 years) completed neuropsychological assessment and brain MRI (1-year post-diagnosis) and parents completed PTSS proxy questionnaires (CRIES-13; 1-3 months and 1-year post-diagnosis). Mean Z-scores and percentage impaired (>1SD) for attention, processing speed, executive functioning, and memory were compared to normscores (t-tests, chi-square tests). Multi-shell diffusion MRI data were analyzed for white matter tractography (fractional anisotropy/axial diffusivity). Effects of PTSS on neurocognition and white matter were explored with linear regression models (FDR correction for multiple testing), including age at diagnosis, treatment intensity, and tumor location as covariates. Neurocognition and limbic white matter associations were explored with correlations. Results: Attention (M = -0.49, 33% impaired; P < .05) and processing speed (M = -0.57, 34% impaired; P < .05) were significantly lower than healthy peers. PTSS was associated with poorer processing speed (ß = -0.64, P < .01). Treatment intensity, age at diagnosis, and tumor location, but not PTSS, were associated with limbic white matter metrics. Neurocognition and white matter metrics were not associated. Conclusions: Higher PTSS was associated with poorer processing speed, highlighting the need for monitoring, and timely referrals to optimize psychological well-being and neurocognitive functioning. Future research should focus on longitudinal follow-up and explore the impact of PTSS interventions on neurocognitive performance.

Improving advanced intraoperative MRI methods during pediatric neurosurgery.

Advanced intraoperative MR images (ioMRI) acquired during the resection of pediatric brain tumors could offer additional physiological information to preserve healthy tissue. With this work, we aimed to develop a protocol for ioMRI with increased sensitivity for arterial spin labeling (ASL) and diffusion MRI (dMRI), optimized for patient positioning regularly used in the pediatric neurosurgery setting. For ethical reasons, ASL images were acquired in healthy adult subjects that were imaged in the prone and supine position. After this, the ASL cerebral blood flow (CBF) was quantified and compared between both positions. To evaluate the impact of the RF coils setups on image quality, we compared different setups (two vs. four RF coils) by looking at T1-weighted (T1w) signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR), as well as undertaking a qualitative evaluation of T1w, T2w, ASL, and dMR images. Mean ASL CBF did not differ between the surgical prone and supine positions in any of the investigated regions of interest or the whole brain. T1w SNR (gray matter: p = 0.016, 34% increase; white matter: p = 0.016, 32% increase) and CNR were higher (p = 0.016) in the four versus two RF coils setups (18.0 ± 1.8 vs. 13.9 ± 1.8). Qualitative evaluation of T1w, T2w, ASL, and dMR images resulted in acceptable to good image quality and did not differ statistically significantly between setups. Only the nonweighted diffusion image maps and corticospinal tract reconstructions yielded higher image quality and reduced susceptibility artifacts with four RF coils. Advanced ioMRI metrics were more precise with four RF coils as the standard deviation decreased. Taken together, we have investigated the practical use of advanced ioMRI during pediatric neurosurgery. We conclude that ASL CBF quantification in the surgical prone position is valid and that ASL and dMRI acquisition with two RF coils can be performed adequately for clinical use. With four versus two RF coils, the SNR of the images increases, and the sensitivity to artifacts reduces.

Quantitative diffusion-weighted MRI response assessment in rhabdomyosarcoma: an international retrospective study on behalf of the European paediatric Soft tissue sarcoma Study Group Imaging Committee.

OBJECTIVE: To investigate the feasibility of diffusion-weighted magnetic resonance imaging (DW-MRI) as a predictive imaging marker after neoadjuvant chemotherapy in patients with rhabdomyosarcoma. MATERIAL AND METHODS: We performed a multicenter retrospective study including pediatric, adolescent and young adult patients with rhabdomyosarcoma, Intergroup Rhabdomyosarcoma Study group III/IV, treated according to the European paediatric Soft tissue sarcoma Study Group (EpSSG) RMS2005 or MTS2008 studies. DW-MRI was performed according to institutional protocols. We performed two-dimensional single-slice tumor delineation. Areas of necrosis or hemorrhage were delineated to be excluded in the primary analysis. Mean, median and 5th and 95th apparent diffusion coefficient (ADC) were extracted. RESULTS: Of 134 included patients, 82 had measurable tumor at diagnosis and response and DW-MRI scans of adequate quality and were included in the analysis. Technical heterogeneity in scan acquisition protocols and scanners was observed. Mean ADC at diagnosis was 1.1 (95% confidence interval [CI]: 1.1-1.2) (all ADC expressed in * 10-3 mm2/s), versus 1.6 (1.5-1.6) at response assessment. The 5th percentile ADC was 0.8 (0.7-0.9) at diagnosis and 1.1 (1.0-1.2) at response. Absolute change in mean ADC after neoadjuvant chemotherapy was 0.4 (0.3-0.5). Exploratory analyses for association between ADC and clinical parameters showed a significant difference in mean ADC at diagnosis for alveolar versus embryonal histology. Landmark analysis at nine weeks after the date of diagnosis showed no significant association (hazard ratio 1.3 [0.6-3.2]) between the mean ADC change and event-free survival. CONCLUSION: A significant change in the 5th percentile and the mean ADC after chemotherapy was observed. Strong heterogeneity was identified in DW-MRI acquisition protocols between centers and in individual patients.

Advanced intraoperative MRI in pediatric brain tumor surgery.

Introduction: In the pediatric brain tumor surgery setting, intraoperative MRI (ioMRI) provides "real-time" imaging, allowing for evaluation of the extent of resection and detection of complications. The use of advanced MRI sequences could potentially provide additional physiological information that may aid in the preservation of healthy brain regions. This review aims to determine the added value of advanced imaging in ioMRI for pediatric brain tumor surgery compared to conventional imaging. Methods: Our systematic literature search identified relevant articles on PubMed using keywords associated with pediatrics, ioMRI, and brain tumors. The literature search was extended using the snowball technique to gather more information on advanced MRI techniques, their technical background, their use in adult ioMRI, and their use in routine pediatric brain tumor care. Results: The available literature was sparse and demonstrated that advanced sequences were used to reconstruct fibers to prevent damage to important structures, provide information on relative cerebral blood flow or abnormal metabolites, or to indicate the onset of hemorrhage or ischemic infarcts. The explorative literature search revealed developments within each advanced MRI field, such as multi-shell diffusion MRI, arterial spin labeling, and amide-proton transfer-weighted imaging, that have been studied in adult ioMRI but have not yet been applied in pediatrics. These techniques could have the potential to provide more accurate fiber tractography, information on intraoperative cerebral perfusion, and to match gadolinium-based T1w images without using a contrast agent. Conclusion: The potential added value of advanced MRI in the intraoperative setting for pediatric brain tumors is to prevent damage to important structures, to provide additional physiological or metabolic information, or to indicate the onset of postoperative changes. Current developments within various advanced ioMRI sequences are promising with regard to providing in-depth tissue information.

Methodological considerations on segmenting rhabdomyosarcoma with diffusion-weighted imaging-What can we do better?

PURPOSE: Diffusion-weighted MRI is a promising technique to monitor response to treatment in pediatric rhabdomyosarcoma. However, its validation in clinical practice remains challenging. This study aims to investigate how the tumor segmentation strategy can affect the apparent diffusion coefficient (ADC) measured in pediatric rhabdomyosarcoma. MATERIALS AND METHODS: A literature review was performed in PubMed using search terms relating to MRI and sarcomas to identify commonly applied segmentation strategies. Seventy-six articles were included, and their presented segmentation methods were evaluated. Commonly reported segmentation strategies were then evaluated on diffusion-weighted imaging of five pediatric rhabdomyosarcoma patients to assess their impact on ADC. RESULTS: We found that studies applied different segmentation strategies to define the shape of the region of interest (ROI)(outline 60%, circular ROI 27%), to define the segmentation volume (2D 44%, multislice 9%, 3D 21%), and to define the segmentation area (excludes edge 7%, excludes other region 19%, specific area 27%, whole tumor 48%). In addition, details of the segmentation strategy are often unreported. When implementing and comparing these strategies on in-house data, we found that excluding necrotic, cystic, and hemorrhagic areas from segmentations resulted in on average 5.6% lower mean ADC. Additionally, the slice location used in 2D segmentation methods could affect ADC by as much as 66%. CONCLUSION: Diffusion-weighted MRI studies in pediatric sarcoma currently employ a variety of segmentation methods. Our study shows that different segmentation strategies can result in vastly different ADC measurements, highlighting the importance to further investigate and standardize segmentation.

Tracking the Corticospinal Tract in Patients With High-Grade Glioma: Clinical Evaluation of Multi-Level Fiber Tracking and Comparison to Conventional Deterministic Approaches.

While the diagnosis of high-grade glioma (HGG) is still associated with a considerably poor prognosis, neurosurgical tumor resection provides an opportunity for prolonged survival and improved quality of life for affected patients. However, successful tumor resection is dependent on a proper surgical planning to avoid surgery-induced functional deficits whilst achieving a maximum extent of resection (EOR). With diffusion magnetic resonance imaging (MRI) providing insight into individual white matter neuroanatomy, the challenge remains to disentangle that information as correctly and as completely as possible. In particular, due to the lack of sensitivity and accuracy, the clinical value of widely used diffusion tensor imaging (DTI)-based tractography is increasingly questioned. We evaluated whether the recently developed multi-level fiber tracking (MLFT) technique can improve tractography of the corticospinal tract (CST) in patients with motor-eloquent HGGs. Forty patients with therapy-naïve HGGs (mean age: 62.6 ± 13.4 years, 57.5% males) and preoperative diffusion MRI [repetition time (TR)/echo time (TE): 5000/78 ms, voxel size: 2x2x2 mm3, one volume at b=0 s/mm2, 32 volumes at b=1000 s/mm2] underwent reconstruction of the CST of the tumor-affected and unaffected hemispheres using MLFT in addition to deterministic DTI-based and deterministic constrained spherical deconvolution (CSD)-based fiber tractography. The brain stem was used as a seeding region, with a motor cortex mask serving as a target region for MLFT and a region of interest (ROI) for the other two algorithms. Application of the MLFT method substantially improved bundle reconstruction, leading to CST bundles with higher radial extent compared to the two other algorithms (delineation of CST fanning with a wider range; median radial extent for tumor-affected vs. unaffected hemisphere - DTI: 19.46° vs. 18.99°, p=0.8931; CSD: 30.54° vs. 27.63°, p=0.0546; MLFT: 81.17° vs. 74.59°, p=0.0134). In addition, reconstructions by MLFT and CSD-based tractography nearly completely included respective bundles derived from DTI-based tractography, which was however favorable for MLFT compared to CSD-based tractography (median coverage of the DTI-based CST for affected vs. unaffected hemispheres - CSD: 68.16% vs. 77.59%, p=0.0075; MLFT: 93.09% vs. 95.49%; p=0.0046). Thus, a more complete picture of the CST in patients with motor-eloquent HGGs might be achieved based on routinely acquired diffusion MRI data using MLFT.

European guideline for imaging in paediatric and adolescent rhabdomyosarcoma - joint statement by the European Paediatric Soft Tissue Sarcoma Study Group, the Cooperative Weichteilsarkom Studiengruppe and the Oncology Task Force of the European Society of Paediatric Radiology.

Appropriate imaging is essential in the treatment of children and adolescents with rhabdomyosarcoma. For adequate stratification and optimal individualised local treatment utilising surgery and radiotherapy, high-quality imaging is crucial. The paediatric radiologist, therefore, is an essential member of the multi-disciplinary team providing clinical care and research. This manuscript presents the European rhabdomyosarcoma imaging guideline, based on the recently developed guideline of the European Paediatric Soft Tissue Sarcoma Study Group (EpSSG) Imaging Committee. This guideline was developed in collaboration between the EpSSG Imaging Committee, the Cooperative Weichteilsarkom Studiengruppe (CWS) Imaging Group, and the Oncology Task Force of the European Society of Paediatric Radiology (ESPR). MRI is recommended, at diagnosis and follow-up, for the evaluation of the primary tumour and its relationship to surrounding tissues, including assessment of neurovascular structures and loco-regional lymphadenopathy. Chest CT along with [F-18]2-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET)/CT or PET/MRI are recommended for the detection and evaluation of loco-regional and distant metastatic disease. Guidance on the estimation of treatment response, optimal long-term follow-up, technical imaging settings and standardised reporting are described. This European imaging guideline outlines the recommendations for imaging in children and adolescents with rhabdomyosarcoma, with the aim to harmonise imaging and to advance patient care.

Zooming in on cerebral small vessel function in small vessel diseases with 7T MRI: Rationale and design of the "ZOOM@SVDs" study.

Background: Cerebral small vessel diseases (SVDs) are a major cause of stroke and dementia. Yet, specific treatment strategies are lacking in part because of a limited understanding of the underlying disease processes. There is therefore an urgent need to study SVDs at their core, the small vessels themselves. Objective: This paper presents the rationale and design of the ZOOM@SVDs study, which aims to establish measures of cerebral small vessel dysfunction on 7T MRI as novel disease markers of SVDs. Methods: ZOOM@SVDs is a prospective observational cohort study with two years follow-up. ZOOM@SVDs recruits participants with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL, N = 20), sporadic SVDs (N = 60), and healthy controls (N = 40). Participants undergo 7T brain MRI to assess different aspects of small vessel function including small vessel reactivity, cerebral perforating artery flow, and pulsatility. Extensive work-up at baseline and follow-up further includes clinical and neuropsychological assessment as well as 3T brain MRI to assess conventional SVD imaging markers. Measures of small vessel dysfunction are compared between patients and controls, and related to the severity of clinical and conventional MRI manifestations of SVDs. Discussion: ZOOM@SVDs will deliver novel markers of cerebral small vessel function in patients with monogenic and sporadic forms of SVDs, and establish their relation with disease burden and progression. These small vessel markers can support etiological studies in SVDs and may serve as surrogate outcome measures in future clinical trials to show target engagement of drugs directed at the small vessels.

Data-Driven Identification of the Regions of Interest for Fiber Tracking in Patients with Brain Tumors.

BACKGROUND: We investigated the added value of combining information from direction-encoded color (DEC) maps with high-resolution structural magnetic resonance imaging scans (T1-weighted images [T1WIs]) to improve the identification of regions of interest (ROIs) for fiber tracking during preoperative planning for patients with brain tumors. METHODS: The dataset included 42 patients with gliomas and 10 healthy subjects from the Human Connectome Project. For identification of the ROIs, we combined the structural information from high-resolution T1WIs and the directional information from DEC maps. To test our hypothesis, we examined the interrater and intrarater agreement. RESULTS: We identified specific ROIs to extract the main white matter bundles. The directional information from the DEC maps combined with the T1WIs (T1WI-DEC maps) had significantly facilitated ROI identification in patients with brain tumors, especially patients in whom the tracts had been displaced by the mass effect of the tumor. Fiber tracking using the combined T1WI-DEC maps showed significantly greater inter- and intrarater agreement compared with using either T1WI or DEC maps alone. CONCLUSION: Combining the information from diffusion-derived color-encoded maps with high-resolution anatomical details from structural imaging (T1WI-DEC map), especially in patients with brain tumors, could be useful for accurate identification of the ROIs.

Laparoscopic treatment of De Garengeot hernia with Progrip.

BACKGROUND: Many eponyms have been used to classify some rare conditions of incarceration of a hernia at the level of the groin and femoral canal. The incarceration of the appendix at the level of the groin canal was first described by Claudius Amyand, while the incarceration of the appendix inside the femoral canal is a condition known as De Garengeot hernia. The incidence of such an event is very low and surgical treatment is usually performed via inguinal approach. CASE PRESENTATION: We describe the case of a 63-year-old woman who presented upon arrival at the Emergency Room a sore tumefaction in the femoral region with skin erythema. The patient had never undergone surgery for groin or femoral hernias. After performing ultrasound reporting the presence of an incarcerated intestinal loop, the patient underwent surgery. Laparoscopic exploration highlighted the presence of a De Garengeot hernia. After exploration, it was decided to continue the laparoscopic operation: at first, the hernia sac was reduced, then a self-gripping mesh was put in place. Finally, after the closure of the peritoneum, the operation was completed by performing a laparoscopic appendectomy. The patient was discharged from hospital three days from surgery with an antibiotic therapy for further two days after discharge. After three months, upon clinical examination, no recurrences of hernia were evident. CONCLUSIONS: We describe a rare case of De Garengeot hernia treated laparoscopically. The treatment of such a condition is not standardized because of the few cases described. The laparoscopic approach should always be considered to perform at least an exploration of the abdominal cavity and evaluate the contents of the hernia sac. Laparoscopic hernia treatment should be carried out by experienced surgeons who are familiar with the technique and apply it routinely. KEY WORDS: Appendicitis, De Garengeot, Hernia, Laparoscopy.

Nasal flap or cutaneous grafting in basal cell cancer of the nose. Comparison of two reconstructive possibilities.

BACKGROUND: Basal cell cancer is a malignant tumor of the skin most common in Caucasians and more common in the areas of the head and neck. At the moment there are many suggested treatment methods, however the surgical approach remains the technique most often applied. It includes excision of the oncological safety margins and the subsequent reconstructive phase can utilize local flaps or cutaneous grafts. This study aims to select the best technique for the reconstructive phase after removal of basal cell cancer from the region of the nasal pyramid, evaluation was made in terms of functional performance and aesthetics. We have evaluated 30 patients, of whom 15 treated with cutaneous grafting and 15 with flaps.

Is human fibrin sealant a possible choice for the fixation of laparoscopic inguinal hernia repair? A single center experience and the analysis of the results after 326 TAPP in two years.

BACKGROUND: Groin hernioplasty is most intervention performed in the worldwide. The present study aimed to evaluate a combination between ultralight mesh and fibrin human sealant in the laparoscopic treatment of inguinal hernia. PATIENTS AND METHODS: This retrospective study included consecutive patients who underwent laparoscopic transabdominal preperitoneal hernioplasty (TAPP) from 1st of January 2015 to 31st of December 2016. Demographics, surgical data and postoperative outcomes were entered in an anonymized prospective database. Prospective longterm follow-up carried out in all patients. RESULTS: One hundred eighty-four patients with a median age 57.5 (range 19-84) and median BMI (Body Mass Index) of 28.5 (range 18.5-31.5) were included. A median follow-up of 25 months (median 13-35) was carried out. Five recurrences (1.5%) and two cases of missed lipoma were observed and operated. Chronic pain (CP) was observed in eleven (9%) patients but in 9 patients it decreased spontaneously. CONCLUSIONS: Combination of ultralight mesh and Evicel® in TAPP operation is a safe solution for the treatment of groin hernia. Recurrences and chronic pain are similar to other combination of fibrin sealant and meshes. Moreover action of Evicel® may provide to improve the hemostasis and consequently hematoma of the cord.

Laparoendoscopic Percutaneous Endoscopic Gastrostomy in Adults.

BACKGROUND: Since its introduction, the placement of percutaneous endoscopic gastrostomy (PEG) has been increasing in the Western countries. Nevertheless, it is not always possible to perform this operation. Laparoscopic-assisted endoscopic gastrostomy (LAPEG) is an effective alternative solution. MATERIALS AND METHODS: Indication to PEG placement was established only for people who required a nutritional support of >4 weeks and without metastatic carcinoma. Sixteen patients underwent LAPEG after the failure of the original PEG operation. Two trocars of 5 mm and one of 12 mm were used, and a fourth trocar of 5 mm was placed when necessary to lift the liver. In four cases a gastrotomy was performed, in seven patients it was not necessary. When PEG was placed, the stomach was not fixed with stitches to the abdominal wall. RESULTS: Sixteen patients were selected for LAPEG and were all successful; in one case it was necessary to replace the PEG, and the same procedure was performed again. Median age was 73 years. Placement of laparoscopic PEG was not associated with other surgical procedures. Nutritional feeding started the day after for patients with sutureless technique and 2 days after in patients with gastrotomy. CONCLUSION: LAPEG is a safe technique with a low complication rate. It should be considered a minimal alternative in all cases where the placement of PEG is not possible.

Paget's disease of the male breast: case report and a point of view from actual literature.

INTRODUCTION: Paget disease of the nipple in man is a very rare breast cancer, and there are not standard procedures or guidelines. In any cases, a Paget's disease could hide an invasive ductal breast cancer. CASE DESCRIPTION: We report the case of a 77-years old man affected by Alzheimer's disease, who presented to our attention because of an ulcerated palpable mass in the right nipple. A biopsy of the lesion showed "intra-epidermic proliferation of epitelioid cells, associated with linfo-plasmacellular infiltration of superficial dermis, compatible with Paget's disease (pTis)". We discussed the case in the multidisciplinary meeting and decided to subject the patient to surgery, so a right mastectomy plus sentinel lymph node biopsy (SLNB) were performed. Histo-pathological examination revealed "invasive ductal carcinoma of the breast, associated with a small component of in situ ductal carcinoma and Paget's disease of the nipple with superficial ulceration". Resection margins were free. Sentinel lymph node was negative. Biological features were as follows: ER 95%, PR 60%, Her-2/neu 1+, Ki-67 35%. The patient was discharged in the third post-operative day in good conditions. In the following weeks the patient's healing process was good and free of complications. CONCLUSIONS: Clinical recognition of Paget's disease is very important also in man, because it can be the alarm bell for an underlying invasive ductal breast cancer, often more aggressive than in woman.