The Precision, Inter-Rater Reliability, and Accuracy of a Handheld Scanner Equipped with a Light Detection and Ranging Sensor in Measuring Parts of the Body-A Preliminary Validation Study.

BACKGROUND: Anthropometric measurements play a crucial role in medico-legal practices. Actually, several scanning technologies are employed in post-mortem investigations for forensic anthropological measurements. This study aims to evaluate the precision, inter-rater reliability, and accuracy of a handheld scanner in measuring various body parts. METHODS: Three independent raters measured seven longitudinal distances using an iPad Pro equipped with a LiDAR sensor and specific software. These measurements were statistically compared to manual measurements conducted by an operator using a laser level and a meterstick (considered the gold standard). RESULTS: The Friedman test revealed minimal intra-rater variability in digital measurements. Inter-rater variability analysis yielded an ICC = 1, signifying high agreement among the three independent raters. Additionally, the accuracy of digital measurements displayed errors below 1.5%. CONCLUSIONS: Preliminary findings demonstrate that the pairing of LiDAR technology with the Polycam app (ver. 3.2.11) and subsequent digital measurements with the MeshLab software (ver. 2022.02) exhibits high precision, inter-rater agreement, and accuracy. Handheld scanners show potential in forensic anthropology due to their simplicity, affordability, and portability. However, further validation studies under real-world conditions are essential to establish the reliability and effectiveness of handheld scanners in medico-legal settings.

Syncope and Cannabis: hypervagotonia from chronic abuse? A case report and literature review.

BACKGROUND: Cannabis is the most consumed drug worldwide and number of users is increasing, particularly among youth. Moreover, cannabis potential therapeutic properties have renewed interest to make it available as a treatment for a variety of conditions. Albeit rarely, cannabis consumption has been associated with cardiovascular diseases such as arrhythmias, myocardial infarction (MI) and potentially sudden death. CASE PRESENTATION: A 24-year-old woman presented to the emergency department sent by her cardiologist because of a recent finding of a 16 seconds asystole on the implantable loop recorder (ILR) she implanted 7 months before for recurrent syncopes. She declared that she is a heavy cannabis user (at least 5 cannabis-cigarette per day, not mixed up with tobacco, for no less than 12 years) and all syncopes occurred shortly after cannabis consumption. After a collective discussion with the heart team, syncope unit, electrophysiologists and toxicologist, we decided to implant a dual chamber pacemaker with a rate response algorithm due to the high risk of trauma of the syncopal episodes. 24 months follow-up period was uneventful. CONCLUSIONS: Cannabis cardiovascular effects are not well known and, although rare, among these we find ischemic episodes, tachyarrhythmias, symptomatic sinus bradycardia, sinus arrest, ventricular asystole and possibly death. Because of cannabis growing consumption both for medical and recreational purpose, cardiovascular diseases associated with cannabis use may become more and more frequent. In the light of the poor literature, we believe that cannabis may produce opposite adverse effects depending on the duration of the habit. Acute administration increases sympathetic tone and reduces parasympathetic tone; conversely, with chronic intake an opposite effect is observed: repetitive dosing decreases sympathetic activity and increases parasympathetic activity. Clinicians should be aware of the increased risk of cardiovascular complications associated with cannabis use and should investigate its consumption especially in young patients presenting with cardiac dysrhythmias.

Phosphatidylethanol (PEth) in Blood as a Marker of Unhealthy Alcohol Use: A Systematic Review with Novel Molecular Insights.

The Alcohol Use Disorders Identification Test (AUDIT) and its short form, the AUDIT-C, the main clinical instruments used to identify unhealthy drinking behaviors, are influenced by memory bias and under-reporting. In recent years, phosphatidylethanol (PEth) in blood has emerged as a marker of unhealthy alcohol use. This systematic review aims to investigate the molecular characteristics of PEth and summarize the last ten years of published literature and its use compared to structured questionnaires. A systematic search was performed, adhering to PRISMA guidelines, through "MeSH" and "free-text" protocols in the databases PubMed, SCOPUS, and Web of Science. The inclusion criteria were as follows: PEth was used for detecting unhealthy alcohol consumption in the general population and quantified in blood through liquid chromatography coupled to mass spectrometry, with full texts in the English language. Quality assessment was performed using the JBI critical appraisal checklist. Twelve papers were included (0.79% of total retrieved records), comprising nine cross-sectional studies and three cohort studies. All studies stratified alcohol exposure and quantified PEth 16:0/18:1 through liquid chromatography coupled to mass spectrometry (LC-MS) in liquid blood or dried blood spots (DBS) with lower limits of quantitation (LLOQ) ranging from 1.7 ng/mL to 20 ng/mL. A correlation between blood PEth level and the amount of alcohol ingested in the previous two weeks was generally observed. PEth interpretative cut-offs varied greatly among the included records, ranging from 4.2 ng/mL to 250 ng/mL, with sensitivity and specificity in the ranges of 58-100% and 64-100%, respectively. Although the biomarker seems promising, further research elucidating the variability in PEth formation and degradation, as well as the molecular mechanisms behind that variability, are necessary.

Long-term results from the multicentric European randomized phase 3 trial CWS/RMS-96 for localized high-risk soft tissue sarcoma in children, adolescents, and young adults.

BACKGROUND: CWS/RMS-96 was an international multicenter trial with randomization between two therapy arms of the standard four-drug therapy (vincristine, ifosfamide, adriamycin, dactinomycin [VAIA]) versus an intensified six-drug regimen (carboplatin, epirubicin, vincristine, dactinomycin, ifosfamide, and etoposide [CEVAIE]) for high-risk rhabdomyosarcoma (RMS), extraskeletal Ewing sarcoma (EES), and undifferentiated sarcoma (UDS) in children, adolescents, and young adults aiming to improve their survival. Intensified chemotherapy with CEVAIE did not improve outcome. METHODS: Patients younger than 21 years with a previously untreated localized HR-RMS, EES, and UDS were enrolled from Cooperative Weichteilsarkom Studiengruppe (CWS) centers in Germany, Austria, Poland, Switzerland, and from Italian Soft Tissue Sarcoma Committee (STSC) centers. Randomization (1:1) to receive either 9 × 21 days cycles of VAIA or CEVAIE was performed separately in CWS and STSC. Hyperfractionated accelerated radiotherapy (32-44.8 Gy) was added at week 9-12 according to histology and response to chemotherapy. A secondary microscopically complete nonmutilating resection was performed if possible. Primary endpoints were response to chemotherapy, event-free (EFS) and overall survival (OS). RESULTS: Five hundred fifty-seven patients (HR-RMS: n = 416, EES and UDS: n = 141) underwent randomization: VAIA (n = 273) or CEVAIE (n = 284). Radiotherapy was given to 70% of patients in both groups. A secondary resection was performed in 47% and 48% patients, respectively. The 5-year EFS and OS for the VAIA and CEVAIE treatment arms were 59.8% and 60.8% (p = .89), and 74.2% and 68.3% (p = .16), respectively. No differences in response, toxicity, or second malignancies emerged in the two groups. CONCLUSION: The use of an intensified regimen failed to show a significant improvement in tumor response and outcome of patients with localized HR-RMS, EES, and UDS.

Entrapment within an ottoman storage bed: an unusual accidental asphyxial death.

Herein, we present an uncommon forensic case of death by asphyxia. The victim was a woman whose body at death scene investigation (DSI) was discovered beside an ottoman storage bed. According to the rescue team, who had moved the body before our arrival, the body was originally found in the prone position and stuck with the neck, thorax and arms within the bed. Examination of the body showed hypostasis that was mainly distributed to the face and the lower chest while sparing the neck and the upper chest. The face was markedly swollen, and the eyes were congested with blood. Dissection and histology revealed pulmonary oedema and emphysema of both lungs. Integrating circumstantial, radiology and autopsy data, it was established that the victim, while trapped between the mattress and the edge of the ottoman storage bed, died by mechanical asphyxia due to cervical-thoracic compression and postural asphyxia acting simultaneously.

Homicide and concealment of the corpse. Autopsy case series and review of the literature.

INTRODUCTION: The concealment of the body following a homicide undermines different moments of the forensic and medico-legal investigations. The aim of the present study is to provide an overview of the literature and the forensic casuistry of the Institute of Legal Medicine of Padova for analyzing and discussing diverse methodological approaches for the forensic pathologist dealing with covered-up homicides. MATERIAL AND METHODS: A literature review, updated until September 2019, was performed, and a literature pool of forensic cases was built. In-house cases were included by conducting a retrospective analysis of the forensic caseworks of Padova of the last 20 years. Data regarding epidemiology, methodology of assessment, methods of concealment, and answers to medico-legal issues were extracted for both data sets. RESULTS AND DISCUSSION: Seventy-eight papers were included in the literature review (78.2% being case reports or case series, 17% retrospective studies, and 6% experimental studies or reviews). Literature and in-house data sets consisted of 145 and 13 cases, respectively. Death scene investigation, radiology, toxicology, and additional analyses were performed in 20-54% of literature and 62-77% of in-house cases. Cover-up by multiple methods prevailed. Death was caused by head trauma in about 40% of cases (both data sets), strangulation in 21% of literature, and 7% of in-house cases, and was undetermined in 17% of literature and 7% of in-house cases. CONCLUSIONS: The methodology of ascertainment should be case-specific and based on a multidisciplinary and multimodal evaluation of all data, including those gained through novel radiological and/or analytical techniques.

Pancreatoblastoma in children: EXPeRT/PARTNER diagnostic and therapeutic recommendations.

Pancreatoblastoma (PBL) is a rare malignant epithelial neoplasm that affects typically young children. Signs related to advanced upper-abdominal tumor accompanied by elevated serum α-fetoprotein levels in a young child suggest PBL, however histopathological confirmation is mandatory. The mainstay of the treatment is a complete surgical resection. Unresectable and/or metastatic PBL may become amenable to complete delayed surgery after neoadjuvant chemotherapy. This manuscript presents the international consensus recommendations for the diagnosis and treatment of children with PBL, established by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) within the EU-funded PARTNER (Paediatric Rare Tumors Network - European Registry) project.

Facing the challenges of very rare tumors of pediatric age: The European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) background, goals, and achievements.

It has become increasingly clear in recent years that we need to develop ad hoc strategies to combat very rare tumors (VRT) of pediatric age. In 2008, several schemes being run in different countries were pooled together to create the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) project: a cooperative study group that aimed to promote research in the relatively uncharted territory of rare tumors of pediatric age. EXPeRT members were able to activate different levels of cooperation to achieve their goals, and to obtain dedicated funding by participating in EU-financed projects. Their experiences emphasize the merits of networking, seeking new partnerships, joining forces, and pooling resources to extend the reach of research efforts, and ultimately improve the quality of patient care. Between 2018 and 2021, the EXPeRT has been active in establishing the Pediatric Rare Tumors Network - European Registry (PARTNER). This project had the main purposes of building a European common registry of pediatric VRT, but also the major task of developing diagnostic and treatment guidelines for VRT (or at least part of them). These clinical recommendations are the subject of a series of papers on Pediatric Blood and Cancer.

Consensus recommendations from the EXPeRT/PARTNER groups for the diagnosis and therapy of sex cord stromal tumors in children and adolescents.

As part of the European Union-funded project designated Paediatric Rare Tumours Network - European Registry (PARTNER), the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) is continuously developing consensus recommendations in order to harmonize standard care for very rare solid tumors of children and adolescents. This paper presents the internationally recognized recommendations for the diagnosis and treatment of sex cord stromal tumors (SCST). The clinical approach to sex cord stromal tumors of the testis (TSCST) and ovary (OSCST) depends on histological differentiation and tumor stage. Virtually all TSCSTs present as localized nonmetastatic tumors, with excellent prognosis after complete resection. In contrast, the prognosis of OSCSTs may be adversely affected by tumor spillage during surgery or presence of metastases. In these cases, cisplatin-based chemotherapy is recommended. Of note, some SCSTs may develop in the context of tumor predisposition syndromes, for example, DICER-1, so that specific follow-up is indicated. SCSTs should be diagnosed and treated according to standardized recommendations that include reference pathology, genetic testing for tumor predisposition syndromes in selected cases, and stratified adjuvant chemotherapy in patients with unfavorable risk profile. To ensure high quality of diagnosis and therapy, patients should be enrolled into prospective registries.

Intra-class and inter-class tool discrimination through micro-CT analysis of false starts on bone.

Micro-CT has successfully been applied to the characterization of false starts (FSs) and, among several parameters, kerf width seems to correlate to the tool blade. The aim of the present study was to evaluate the diagnostic value of micro-CT for the differentiation of saw marks produced by different classes of saws and by saws belonging to the same class and differing only in number of teeth per inches (TPI). A morphological and morphometric analysis of 84 marks, produced by 6 saws belonging to 3 morphological classes, was performed. In the experimental cohort, for each parameter, statistically significant differences in intra- and inter-class analysis were searched for and cut-offs were established. The diagnostic accuracy of cut-offs was assessed through statistical analyses on the validation cohort. The morphological assessment did not allow to differentiate saws differing only in TPI. Angle 1 and top kerf width, respectively for cross-cut and rip-cut saws with alternating set, allowed a good discrimination between FSs produced by tools belonging to the same morphological class. High positive predictive values were found in intra-class analyses, while results in inter-class analyses were less encouraging. In cases of dismemberment, a micro-CT-based analysis of FSs is strongly suggested as a part of a multistep and multimodal methodology of assessment, which includes scanning electron microscopy and stereomicroscopy. A morphological assessment should be followed by an experimental trial and by a morphometric analysis. Further studies are needed to evaluate hampering factors, such as damage by physico-chemical agents.

Pheochromocytomas and paragangliomas in children: Data from the Italian Cooperative Study (TREP).

BACKGROUND: Pheochromocytomas (PCs) are neuroendocrine tumors arising from the chromaffin cells of the adrenal gland, and paragangliomas (PGLs) are their extra-adrenal counterparts arising from ganglia along the sympathetic/parasympathetic chain. Surgery is the cornerstone of treatment. A sporatic or inherited germline mutation is commonly associated. MATERIALS AND METHODS: Among over 1000 patients registered into the Tumori Rari in Età Pediatrica-rare tumors in pediatric age project-from 2000 to 2019, 50 were affected by PC/PGL. All clinical and therapeutic data were evaluated. RESULTS: Twenty-eight patients had PC and 22 had PGL. Age at diagnosis ranged between 5 and 17 years. Thirty-five patients had symptoms related to catecholamine hypersecretion; in 7 of 50 patients, diagnosis was incidental or done during assessment of a familial syndrome. In all cases, conventional imaging was effective to assess the presence of a tumor. In addition, 18 of 38 functional imaging studies were positive (61%). Forty-eight patients were eligible for surgery: a complete resection was more frequently achieved in PC than in PGL (26/28 vs 11/22). All relapses were treated with surgery alone, surgery plus medical treatment, or chemotherapy alone; one PC with metastasis at diagnosis received radiotherapy only. Forty-four patients were in the first, second, or third complete remission (10/50 recurred; 8/10 carried a germline mutation). Five of 50 patients were alive with disease. One patient died of disease. CONCLUSIONS: Surgery can be curative in most tumors but it may not be always effective in removing PGLs. Severe postsurgical sequelae may affect these patients. Genetic tests should always be considered in individuals affected, and genetic counseling should be offered to their families.

Radiological investigation of gunshot wounds: a systematic review of published evidence.

INTRODUCTION: Despite the constantly growing popularity of radiological imaging in forensic pathology, a systematic review investigating the efficiency and limits of radiological techniques, in comparison to forensic autopsy, was still missing. AIM: The present review aims at providing an overview on the current role of radiology in the forensic investigation of fatal gunshot wounds without any restriction to specific radiological techniques. MATERIAL AND METHODS: A systematic literature search on three databases (PubMed, Web of Science, and Science Direct) was performed until December 2017. The Oxford Centre for Evidence Based Medicine (OCEBM) grading system for levels of evidence was applied, in order to weigh published evidence. RESULTS AND DISCUSSION: Eighty-six papers (1.64% of the records) were included. Despite the quite limited general level of evidence, which contrasts with the abundance of the scientific literature on this topic, several recommendations/statements, coupled to their OCEBM grade, were distilled as for the identification of retained bullets, gunshot wounds detection, diagnosis of entrance and exit wounds, trajectories and internal injury detection and estimation of the firing distance. CONCLUSIONS: Imaging radiological technologies represent the present and future of wound ballistics. However, traditional, micro and molecular imaging techniques require further validation through blinded cross-sectional studies with appropriate reference standards (e.g. forensic autopsy).

Post-mortem thermal angiography: a pilot study on swine coronary circulation.

Thermal imaging (TI) allows the detection of thermal patterns emitted from objects as a function of their temperature in the long-infrared spectrum and produces visible images displaying temperature differences. The aim of this pilot study was to test TI to visualize the coronary circulation of swine hearts. Thirty swine hearts were prepared for ex situ coronarography, and thermal images were acquired through a FlirOne thermal camera (FLIR Systems®) paired with a Google Android Smartphone. Coronary arteries were cannulated, namely the anterior interventricular artery, the circumflex branch of the left coronary artery, and the right coronary artery. The heart was cooled, and contrast medium (CM) consisting of distilled water heated to 40 °C was injected in a coronary vessel, while thermal images were captured. These steps were repeated for each coronary vessel and under experimentally simulated coronary heart disease. Thermal imaging coronarography (TIC) allowed a clear representation of the morphology and course of the coronary vessels and of experimentally simulated coronary heart disease, moreover, demonstrated to be easy to perform during or after autopsies on ex situ hearts, non-destructive, reproducible, and cheap. On the basis of these preliminary results, TIC might allow a subsequent more focused and comprehensive cardiopathological examination of the heart, which remains mandatory for the definitive diagnosis of coronary heart disease. Although these preliminary results seem encouraging, further systematic studies on human hearts, both normal and pathological, are necessary for estimating the sensitivity and specificity of the proposed method and to draw any definitive conclusion.

Outcome after surgery for solid pseudopapillary pancreatic tumors in children: Report from the TREP project-Italian Rare Tumors Study Group.

BACKGROUND: Solid pseudopapillary pancreatic tumors (SPPT) are an extremely rare entity in pediatric patients. Even if the role of radical surgical resection as primary treatment is well established, data about follow-up after pancreatic resection in children are scant. METHODS: A retrospective review of data from the Italian Pediatric Rare Tumor Registry (TREP) was performed. Short-term (<30 days) and long-term complications of different surgical resections, as well as long-term follow-up were evaluated. RESULTS: From January 2000 to present, 43 patients (male:female = 8:35) were enrolled. The median age at diagnosis was 13.2 years (range, 7-18). Nine children had an incidental diagnosis, whereas 26 complained of abdominal pain and 4 of palpable mass. Tumors arose either from the head of pancreas (n = 14) or from body/tail (n = 29): only one patient presented with metastatic disease. Resection was complete in all patients (cephalic duodenopancreatectomy vs distal resection). At follow-up (median, 8.4 years; range, 0-17 years), one recurrence occurred in a patient with intraoperative rupture. All patients are alive. Three pancreatic fistulas occurred in the body/tail group, whereas four complications occurred in the head group (one ileal ischemia, two stenosis of the pancreatic duct, and one chylous fistula). CONCLUSION: Surgery is the best therapeutic option for these tumors; hence, complete resection is mandatory. Extensive resections, including cephalic duodenopancreatectomy, are safe when performed in specialized centers. Long-term follow-up should be aimed to detect tumor recurrence and to evaluate residual pancreatic function.

Necrotizing fasciitis: case series and review of the literature on clinical and medico-legal diagnostic challenges.

Necrotizing fasciitis (NF) is a life-threatening infection of soft tissues spreading along the fasciae to the surrounding musculature, subcutaneous fat and overlying skin areas that can rapidly lead to septic shock and death. Due to the pandemic increase of medical malpractice lawsuits, above all in Western countries, the forensic pathologist is frequently asked to investigate post-mortem cases of NF in order to determine the cause of death and to identify any related negligence and/or medical error. Herein, we review the medical literature dealing with cases of NF in a post-mortem setting, present a case series of seven NF fatalities and discuss the main ante-mortem and post-mortem diagnostic challenges of both clinical and forensic interests. In particular, we address the following issues: (1) origin of soft tissue infections, (2) micro-organisms involved, (3) time of progression of the infection to NF, (4) clinical and histological staging of NF and (5) pros and cons of clinical and laboratory scores, specific forensic issues related to the reconstruction of the ideal medical conduct and the evaluation of the causal value/link of any eventual medical error.

Pediatric patients with cutaneous melanoma: A European study.

INTRODUCTION: Cutaneous melanoma is rare in childhood and published studies have mainly been retrospective single-institution series or small case series. Given the absence of clinical protocols dedicated to pediatric melanoma, the treatment approach is generally extrapolated from the ones applied to adults. METHODS: Coordinated by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT), this study collected patients prospectively registered between 2002 and 2012 under national cooperative projects dedicated to rare pediatric tumors in Italy, Poland, Germany, and France. Additional cases were collected from dermatology registries in Germany and Israel. RESULTS: A total of 219 patients aged 0-18 years (median 14.4) were included in the analysis. Sentinel lymph node biopsy was performed in 112 patients (76% of those with Breslow thickness > 0.75 mm) and was positive in 37.5%. Systemic therapy was used in 33 cases. In stage III cases, survival rates were similar for patients who received (23 cases) or not (21 cases) adjuvant therapy. For the whole series, 3-year overall and disease-free survival rates were 91.4% and 84.0%, respectively (median follow-up 41.8 months). Tumor site, tumor stage, and ulceration influenced survival rates. Patients treated by pediatric oncologists (n = 140) were more likely to have advanced disease than those treated by dermatologists (n = 79). DISCUSSION: This study would suggest that the clinical history of melanoma in children and adolescents might resemble that of adult counterpart. Cooperative efforts are needed to make new drugs more readily available to pediatric patients to increase the outcome of patient with advanced disease.

Novel Therapy for Pediatric Angiosarcoma With Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

The management of pediatric abdominopelvic angiosarcoma remains unclear due to limited clinical experience. Herein, we presented the first 2 pediatric patients with abdominal angiosarcoma who were treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) after neoadjuvant therapy. The first patient is alive with recurrent disease at 1-year follow-up and the second patient remains disease free after 1 year. CRS and HIPEC should be considered as a therapeutic option in the management of pediatric abdominal angiosarcomas. A multi-institutional international shared registry is needed to further evaluate the role of CRS and HIPEC in inducing remission of abdominopelvic angiosarcomas in the pediatric population.

Back to the Future - Part 1. The medico-legal autopsy from ancient civilization to the post-genomic era.

Part 1 of the review "Back to the Future" examines the historical evolution of the medico-legal autopsy and microscopy techniques, from Ancient Civilization to the Post-Genomic Era. In the section focusing on "The Past", the study of historical sources concerning the origins and development of the medico-legal autopsy, from the Bronze Age until the Middle Ages, shows how, as early as 2000 BC, the performance of autopsies for medico-legal purposes was a known and widespread practice in some ancient civilizations in Egypt, the Far East and later in Europe. In the section focusing on "The Present", the improvement of autopsy techniques by Friedrich Albert Zenker and Rudolf Virchow and the contemporary development of optical microscopy techniques for forensic purposes during the 19th and 20th centuries are reported, emphasizing, the regulation of medico-legal autopsies in diverse nations around the world and the publication of international guidelines or best practices elaborated by International Scientific Societies. Finally, in "The Future" section, innovative robotized and advanced microscopy systems and techniques, including their possible use in the bio-medicolegal field, are reported, which should lead to the improvement and standardization of the autopsy methodology, thereby achieving a more precise identification of natural and traumatic pathologies.

Back to the Future - Part 2. Post-mortem assessment and evolutionary role of the bio-medicolegal sciences.

Part 2 of the review "Back to the Future" is dedicated to the evolutionary role of the bio-medicolegal sciences, reporting the historical profiles, the state of the art, and prospects for future development of the main related techniques and methods of the ancillary disciplines that have risen to the role of "autonomous" sciences, namely, Genetics and Genomics, Toxicology, Radiology, and Imaging, involved in historic synergy in the "post-mortem assessment," together with the mother discipline Legal Medicine, by way of its primary fundament, universally denominated as Forensic Pathology. The evolution of the scientific research and the increased accuracy of the various disciplines will be oriented towards the elaboration of an "algorithm," able to weigh the value of "evidence" placed at the disposal of the "justice system" as real truth and proof.

Image-defined risk factors in unresectable neuroblastoma: SIOPEN study on incidence, chemotherapy-induced variation, and impact on surgical outcomes.

PURPOSE: To evaluate the impact of image-defined risk factor (IDRF) modification after chemotherapy on surgical outcomes, event-free survival (EFS), and overall survival (OS) among patients enrolled in the European Unresectable Neuroblastoma (EUNB) study. METHODS: IDRFs were assigned according to the corresponding surgical risk factors list reported in the database. Surgical outcomes, EFS, and OS were related to IDRF modification with chemotherapy. The predictive value of preoperative IDRF for surgical outcomes was analyzed. Cox proportional hazards models for EFS and OS, including preoperative IDRF, surgical outcomes, and other known clinical risk factors, were created. RESULTS: Of the 160 patients enrolled in the EUNB study, 143 patients met the inclusion criteria. A total of 228 IDRF were thus collected. Following chemotherapy, 76 (33%) IDRF disappeared in 32.2% of patients, 33 (14%) new IDRF appeared in 18.8% of patients, and 49% of patients did not show any IDRF change. Complete resection/minimal residual disease (71.2%) was more frequent among children who had disappearance/numerical reduction of IDRF (P = 0.005). Infiltration of the branches of the mesenteric artery was predictive of an unfavorable surgical outcome. Prolonged preoperative chemotherapy over five courses and encasement of the celiac axis and/or mesenteric artery origin impacted EFS and OS. CONCLUSIONS: The unchanged IDRF pattern in 50% of patients and the appearance of new IDRF during chemotherapy in approximately 20% of patients strengthens the idea that prolonged chemotherapy is useless for improving surgical resection in this population of patients. In addition, midline perivascular abdominal preoperative IDRF appeared to be predictive not only of surgical outcomes but also of EFS and OS.