Advancements in Neuroendocrine Neoplasms: Imaging and Future Frontiers.

Neuroendocrine neoplasms (NENs) are a diverse group of tumors with varying clinical behaviors. Their incidence has risen due to increased awareness, improved diagnostics, and aging populations. The 2019 World Health Organization classification emphasizes integrating radiology and histopathology to characterize NENs and create personalized treatment plans. Imaging methods like CT, MRI, and PET/CT are crucial for detection, staging, treatment planning, and monitoring, but each of them poses different interpretative challenges and none are immune to pitfalls. Treatment options include surgery, targeted therapies, and chemotherapy, based on the tumor type, stage, and patient-specific factors. This review aims to provide insights into the latest developments and challenges in NEN imaging, diagnosis, and management.

Dual-energy CT applications on liver imaging: what radiologists and radiographers should know? A systematic review.

PURPOSE: This review aims to provide a comprehensive summary of DECT techniques, acquisition workflows, and post-processing methods. By doing so, we aim to elucidate the advantages and disadvantages of DECT compared to conventional single-energy CT imaging. METHODS: A systematic search was conducted on MEDLINE/EMBASE for DECT studies in liver imaging published between 1980 and 2024. Information regarding study design and endpoints, patient characteristics, DECT technical parameters, radiation dose, iodinated contrast agent (ICA) administration and postprocessing methods were extracted. Technical parameters, including DECT phase, field of view, pitch, collimation, rotation time, arterial phase timing (from injection), and venous timing (from injection) from the included studies were reported, along with formal narrative synthesis of main DECT applications for liver imaging. RESULTS: Out of the initially identified 234 articles, 153 met the inclusion criteria. Extensive variability in acquisition parameters was observed, except for tube voltage (80/140 kVp combination reported in 50% of articles) and ICA administration (1.5 mL/kg at 3-4 mL/s, reported in 91% of articles). Radiation dose information was provided in only 40% of articles (range: 6-80 mGy), and virtual non-contrast imaging (VNC) emerged as a common strategy to reduce the radiation dose. The primary application of DECT post-processed images was in detecting focal liver lesions (47% of articles), with predominance of study focusing on hepatocellular carcinoma (HCC) (27%). Furthermore, a significant proportion of the articles (16%) focused on enhancing DECT protocols, while 15% explored metastasis detection. CONCLUSION: Our review recommends using 80/140 kVp tube voltage with 1.5 mL/kg ICA at 3-4 mL/s flow rate. Post-processing should include low keV-VMI for enhanced lesion detection, IMs for tumor iodine content evaluation, and VNC for dose reduction. However, heterogeneous literature hinders protocol standardization.

Focal Liver Lesions in Budd-Chiari Syndrome: Spectrum of Imaging Findings.

Budd-Chiari syndrome (BCS) is a rare clinical entity characterized by hepatic venous outflow obstruction, resulting in liver congestion and subsequent chronic parenchymal damage. This condition often leads to the development of focal liver lesions, including benign focal nodular hyperplasia-like regenerative nodules, hepatocellular carcinoma, and perfusion-related pseudo-lesions. Computed tomography, ultrasound, and magnetic resonance are the commonly employed imaging modalities for the follow-up of BCS patients and for the detection and characterization of new-onset lesions. The accurate differentiation between benign and malignant nodules is crucial for optimal patient management and treatment planning. However, it can be challenging due to the variable and overlapping characteristics observed. This review aims to provide a comprehensive overview of the imaging features and differential diagnosis of focal liver lesions in BCS, emphasizing the key findings and discussing the challenges associated with their interpretation, with the purpose of facilitating the subsequent clinical decision-making.

Echo-Endoscopy Combined with Virtual Reality: A Whole Perspective of Laparoscopic Common Bile Duct Exploration in Children.

Introduction: Endoscopic procedures are performed more frequently in children due to technological advances that can be safely performed in an adequate setting with a support of a multidisciplinary team. Pediatric indications for ERCP (endoscopic retrograde cholangiopancreatography) and EUS (endoscopic ultrasound) occur mainly due to congenital malformations. In a pediatric case series, we report the application of EUS combined with duodenoscopy, eventually associated with ERCP and minimally invasive surgery, highlighting the importance of defining a tailored dedicated management pathway for each patient. Patients and methods: A series of 12 patients, managed at our Center in the last three years, were evaluated, and their management was discussed. Results: EUS was performed in eight patients and permitted the differential diagnosis of duplication cysts and the visualization of the biliary tree and pancreatic anatomy. ERCP was attempted in five patients: in one case, it permitted the preservation of pancreatic tissue, postponing surgery and in three patients, it was technically unfeasible. MIS (minimally invasive surgery) was performed in seven patients, two with laparoscopic common bile duct exploration (LCBDE). Precise anatomical definition and the possibility of surgical simulation and team sharing were evaluated under VR HMD (Virtual Reality Head Mounted Display) in four cases. Conclusions: Exploration of the common bile duct in children differs from that of the adult population and combines echo-endoscopy and ERCP. The integrated use of minimally invasive surgery in the pediatric area is necessary for the whole management perspective in complex malformations and small patients. The introduction in the clinical practice of a preoperative study with Virtual Reality allows a better survey of the malformation and a tailored treatment.

Multimodal treatment with curative intent in a germline BRCA2 mutant metastatic ampullary adenocarcinoma: a case report.

BACKGROUND: Cancers of the Vater ampulla (ampullary cancers, ACs) account for less than 1% of all gastrointestinal tumors. ACs are usually diagnosed at advanced stage, with poor prognosis and limited therapeutic options. BRCA2 mutations are identified in up to 14% of ACs and, differently from other tumor types, therapeutic implications remain to be defined. Here, we report a clinical case of a metastatic AC patient in which the identification of a BRCA2 germline mutation drove a personalized multimodal approach with curative-intent. CASE PRESENTATION: A 42-year-old woman diagnosed with stage IV BRCA2 germline mutant AC underwent platinum-based first line treatment achieving major tumor response but also life-threatening toxicity. Based on this, as well as on molecular findings and expected low impact of available systemic treatment options, the patient underwent radical complete surgical resection of both primary tumor and metastatic lesions. Following an isolated retroperitoneal nodal recurrence, given the expected enhanced sensitivity to radiotherapy in BRCA2 mutant cancers, the patient underwent imaging-guided radiotherapy leading to long-lasting complete tumor remission. After more than 2 years, the disease remains radiologically and biochemically undetectable. The patient accessed a dedicated screening program for BRCA2 germline mutation carriers and underwent prophylactic bilateral oophorectomy. CONCLUSIONS: Even considering the intrinsic limitations of a single clinical report, we suggest that the finding of BRCA germline mutations in ACs should be taken into consideration, together with other clinical variables, given their potential association with remarkable response to cytotoxic chemotherapy that might be burdened with enhanced toxicity. Accordingly, BRCA1/2 mutations might offer the opportunity of personalizing treatment beyond PARP inhibitors up to the choice of a multimodal approach with curative-intent.

Stem Cell Injection for Complex Refractory Perianal Fistulas in Crohn's Disease: A Single Center Initial Experience.

From 30 to 70% of patients with Crohn's disease (CD) may develop perianal fistulas during their lifetime. The medical and surgical management of this complication is challenging, and its treatment still gives unsatisfactory results. However, recent studies on adipose-derived mesenchymal stem cells have proven their anti-inflammatory and immuno-modulatory potential, representing a new promising tool in the treatment of such stubborn disease. We report our initial experience with three patients who had recurrent perianal CD treated with local infiltration of stem cell darvadstrocel (Alofisel). All the patients had a long history of perianal disease refractory to multiple medical and surgical treatments. The preoperative workup included transperineal ultrasound (TP-US), pelvic MRI, and colonoscopy that ruled out active proctitis in all the patients. The post-treatment follow-up included clinical assessment at 1, 3, and 6 months with repeated MRI and TP-US at 6 months. At 6 months, 2 patients had a clinical response despite radiological persistence of fistula tracts, while one patient presented perianal fistula recurrence complicated by perianal abscess. Although our experience is limited to 3 patients and a short follow-up, our results confirm that darvadstrocel injection is a safe procedure, with a good clinical response in most of the patients, but that it apparently had no effect on the anatomical modification of the fistula tracts. Long-term results, with a rigorous assessment of anatomical lesions, are still needed to support the promising data of the literature.

Developing Virtual Reality Head Mounted Display (HMD) Set-Up for Thoracoscopic Surgery of Complex Congenital Lung MalFormations in Children.

Video assisted thoracoscopic surgery (VATS) has been adopted in pediatric age for the treatment of congenital lung malformations (CLM). The success of VATS in pediatrics largely depends on the surgeon's skill ability to understand the airways, vascular system and lung parenchyma anatomy in CLM. In the last years, virtual reality (VR) and 3-dimensional (3D) printing of organ models and VR head mounted display (HMD) technologies have been introduced for completion of preoperative planning in adult patients. To date no reports about the use of VR HMD technologies in a pediatric setting are available. The aim of this report is to introduce a VR HMD model in VATS procedure to improve the quality of care in children with CLM. VR HMD set-up for planning thoracoscopic surgery was performed in a series of pediatric patients with diagnosis of CLM. The preoperative VR HMD evaluation allowed a navigation into the malformation with the aim to explore, interact, and make the surgeon more confident and skilled to answer to the traps. A development of surgical simulations models and teaching program dedicated to education and training in pediatric VATS is suitable among the pediatric surgery community. Further studies should demonstrate all the benefits of such technology in pediatric patients submitted to VATS procedure.

Delta-Radiomics Predicts Response to First-Line Oxaliplatin-Based Chemotherapy in Colorectal Cancer Patients with Liver Metastases.

The purpose of this paper is to develop and validate a delta-radiomics score to predict the response of individual colorectal cancer liver metastases (lmCRC) to first-line FOLFOX chemotherapy. Three hundred one lmCRC were manually segmented on both CT performed at baseline and after the first cycle of first-line FOLFOX, and 107 radiomics features were computed by subtracting textural features of CT at baseline from those at timepoint 1 (TP1). LmCRC were classified as nonresponders (R-) if they showed progression of disease (PD), according to RECIST1.1, before 8 months, and as responders (R+), otherwise. After feature selection, we developed a decision tree statistical model trained using all lmCRC coming from one hospital. The final output was a delta-radiomics signature subsequently validated on an external dataset. Sensitivity, specificity, positive (PPV), and negative (NPV) predictive values in correctly classifying individual lesions were assessed on both datasets. Per-lesion sensitivity, specificity, PPV, and NPV were 99%, 94%, 95%, 99%, 85%, 92%, 90%, and 87%, respectively, in the training and validation datasets. The delta-radiomics signature was able to reliably predict R- lmCRC, which were wrongly classified by lesion RECIST as R+ at TP1, (93%, averaging training and validation set, versus 67% of RECIST). The delta-radiomics signature developed in this study can reliably predict the response of individual lmCRC to oxaliplatin-based chemotherapy. Lesions forecasted as poor or nonresponders by the signature could be further investigated, potentially paving the way to lesion-specific therapies.

Comparison of radiomics approaches to predict resistance to 1st line chemotherapy in liver metastatic colorectal cancer.

Colorectal cancer (CRC) has the second-highest tumor incidence and is a leading cause of death by cancer. Nearly 20% of patients with CRC will have metastases (mts) at the time of diagnosis, and more than 50% of patients with CRC develop metastases during their disease. Unfortunately, only 45% of patients after a chemotherapy will respond to treatment. The aim of this study is to develop and validate a machine learning algorithm to predict response of individual liver mts, using CT scans. Understanding which mts will respond or not will help clinicians in providing a more efficient per-lesion treatment based on patient specific response and not only following a standard treatment. A group of 92 patients was enrolled from two Italian institutions. CT scans were collected, and the portal venous phase was manually segmented by an expert radiologist. Then, 75 radiomics features were extracted both from 7x7 ROIs that moved across the image and from the whole 3D mts. Feature selection was performed using a genetic algorithm. Results are presented as a comparison of the two different approaches of features extraction and different classification algorithms. Accuracy (ACC), sensitivity (SE), specificity (SP), negative and positive predictive values (NPV and PPV) were evaluated for all lesions (per-lesion analysis) and patients (per-patient analysis) in the construction and validation sets. Best results were obtained in the per-lesion analysis from the 3D approach using a Support Vector Machine as classifier. We reached on the training set an ACC of 81%, while on test set, we obtained SE of 76%, SP of 67%, PPV of 69% and NPV of 75%. On the validation set a SE of 61%, SP of 60%, PPV of 57% and NPV of 64% were reached. The promising results obtained in the validation dataset should be extended to a larger cohort of patient to further validate our method.Clinical Relevance- to develop a radiomics signatures predicting single liver mts response to therapy. A personalized mts approach is important to avoid unnecessary toxicity offering more suitable treatments and a better quality of life to oncological patients.

Hybrid Additive Fabrication of a Transparent Liver with Biosimilar Haptic Response for Preoperative Planning.

Due to the complexity of liver surgery, the interest in 3D printing is constantly increasing among hepatobiliary surgeons. The aim of this study was to produce a patient-specific transparent life-sized liver model with tissue-like haptic properties by combining additive manufacturing and 3D moulding. A multistep pipeline was adopted to obtain accurate 3D printable models. Semiautomatic segmentation and registration of routine medical imaging using 3D Slicer software allowed to obtain digital objects representing the structures of interest (liver parenchyma, vasculo-biliary branching, and intrahepatic lesion). The virtual models were used as the source data for a hybrid fabrication process based on additive manufacturing using soft resins and casting of tissue-mimicking silicone-based blend into 3D moulds. The model of the haptic liver reproduced with high fidelity the vasculo-biliary branching and the relationship with the intrahepatic lesion embedded into the transparent parenchyma. It offered high-quality haptic perception and a remarkable degree of surgical and anatomical information. Our 3D transparent model with haptic properties can help surgeons understand the spatial changes of intrahepatic structures during surgical manoeuvres, optimising preoperative surgical planning.

Emergency Department Resuscitative Thoracotomy: Indications, surgical procedure and outcome. A narrative review.

BACKGROUND: Emergency Department Thoracotomy (EDRT) after traumatic Cardio-pulmonary Arrest (CPR) can be used to salvage select critically injured patients. Indications of this surgical procedure are widely debated and changed during last decades. We provide the available literature about EDRT in the effort to provide a comprehensive synthesis about the procedure, likelihood of success and patient's outcome in the different clinical setting, accepted indications and technical details adopted during the procedure for different trauma injuries. METHODS: Literature from 1975 to 2020 was retrieved from multiple databases and reviewed. Indications, contraindications, total number and outcome of patients submitted to EDRT were primary endpoints. RESULTS: A total number of 7236 patients received EDRT, but only 7.8% survived. Penetrating trauma and witnessed cardiopulmonary arrest with the presence of vital signs at the trauma center are the most favorable conditions to perform EDRT. CONCLUSIONS: EDRT should be reserved for acute resuscitation of selected dying trauma patient. Risks of futility, costs, benefits of the surgical procedure should be carefully evaluated before performing the surgical procedure.

Impact of inter-reader contouring variability on textural radiomics of colorectal liver metastases.

BACKGROUND: Radiomics is expected to improve the management of metastatic colorectal cancer (CRC). We aimed at evaluating the impact of liver lesion contouring as a source of variability on radiomic features (RFs). METHODS: After Ethics Committee approval, 70 liver metastases in 17 CRC patients were segmented on contrast-enhanced computed tomography scans by two residents and checked by experienced radiologists. RFs from grey level co-occurrence and run length matrices were extracted from three-dimensional (3D) regions of interest (ROIs) and the largest two-dimensional (2D) ROIs. Inter-reader variability was evaluated with Dice coefficient and Hausdorff distance, whilst its impact on RFs was assessed using mean relative change (MRC) and intraclass correlation coefficient (ICC). For the main lesion of each patient, one reader also segmented a circular ROI on the same image used for the 2D ROI. RESULTS: The best inter-reader contouring agreement was observed for 2D ROIs according to both Dice coefficient (median 0.85, interquartile range 0.78-0.89) and Hausdorff distance (0.21 mm, 0.14-0.31 mm). Comparing RF values, MRC ranged 0-752% for 2D and 0-1567% for 3D. For 24/32 RFs (75%), MRC was lower for 2D than for 3D. An ICC > 0.90 was observed for more RFs for 2D (53%) than for 3D (34%). Only 2/32 RFs (6%) showed a variability between 2D and circular ROIs higher than inter-reader variability. CONCLUSIONS: A 2D contouring approach may help mitigate overall inter-reader variability, albeit stable RFs can be extracted from both 3D and 2D segmentations of CRC liver metastases.

Radiomics predicts response of individual HER2-amplified colorectal cancer liver metastases in patients treated with HER2-targeted therapy.

The aim of our study was to develop and validate a machine learning algorithm to predict response of individual HER2-amplified colorectal cancer liver metastases (lmCRC) undergoing dual HER2-targeted therapy. Twenty-four radiomics features were extracted after 3D manual segmentation of 141 lmCRC on pretreatment portal CT scans of a cohort including 38 HER2-amplified patients; feature selection was then performed using genetic algorithms. lmCRC were classified as nonresponders (R-), if their largest diameter increased more than 10% at a CT scan performed after 3 months of treatment, responders (R+) otherwise. Sensitivity, specificity, negative (NPV) and positive (PPV) predictive values in correctly classifying individual lesion and overall patient response were assessed on a training dataset and then validated on a second dataset using a Gaussian naïve Bayesian classifier. Per-lesion sensitivity, specificity, NPV and PPV were 89%, 85%, 93%, 78% and 90%, 42%, 73%, 71% respectively in the testing and validation datasets. Per-patient sensitivity and specificity were 92% and 86%. Heterogeneous response was observed in 9 of 38 patients (24%). Five of nine patients were carriers of nonresponder lesions correctly classified as such by our radiomics signature, including four of seven harboring only one nonresponder lesion. The developed method has been proven effective in predicting behavior of individual metastases to targeted treatment in a cohort of HER2 amplified patients. The model accurately detects responder lesions and identifies nonresponder lesions in patients with heterogeneous response, potentially paving the way to multimodal treatment in selected patients. Further validation will be needed to confirm our findings.

Standardization of CT radiomics features for multi-center analysis: impact of software settings and parameters.

The aim of this multicentric study is an inter-center benchmarking, to assess how different set tools applied to the same radiomics workflow affected the radiomics features (RFs) values. This topic is of key importance to start collaboration between different centers and to bring radiomic studies from benchmark to bedside. A per-lesion analysis was performed on 56 metastases (mts) selected from 14 patients. A single radiologist performed the segmentation of all mts, and RFs were extracted from the same segmentation of each mts, using two different software and file formats. Potential sources of discrepancies were evaluated. The intraclass correlation coefficient was used to describe how strongly the same radiomic measurements calculated in the two different centers resemble each other. Moreover, means of the relative changes of each RF were calculated, compared and gradually reduced. We showed that, after matching all formulas, discrepancies in RFs calculation between two centers ranged from 1% to 277%. Therefore, we evaluated other sources of variability using a stepwise approach, which led us to reduce the inter-center discrepancies to 0% for 22/25 RFs and below 2% for 3 RFs out of 25. In this study we demonstrated that different radiomic applications and masks formats might strongly impact the computation of some RFs. Therefore, when dealing with multi-center studies it is mandatory to adopt all strategies that can help in limiting the differences, thus keeping in mind the feasibility of these strategies in large cohort studies.

Grade IV Liver Injury Following Mechanical Cardiopulmonary Resuscitation with Postoperative Three-dimensional Evaluation.

A 48-year-old female presented to the emergency department with chest pain and collapsed at the front desk. She was reanimated with mechanical chest compression, and after coronary angiography, a left anterior descending/diagonal bifurcation mini-crush stenting was performed. Few hours after the procedure, the patient showed severe hypotension. Abdominal ultrasound and computed tomography (CT) scan evidenced a massive subcapsular liver hematoma (Grade IV, American association for the surgery of trauma (AAST) liver injury scale) of the right lobe with extrahepatic blushing. Transhepatic embolization was attempted but without benefit, so the patient underwent emergency laparotomy for damage control surgery with perihepatic packing. After hemodynamic stabilization, right hepatectomy was performed with a favorable outcome and full recovery. The patient CT scan was retrospectively processed to obtain a virtual model visualizable through a head-mounted display. The virtual reconstruction could improve the comprehension of the injury and the liver surgical anatomy for educational purpose, and it could represent a new tool for preoperative planning.

A Virtual Reality Environment to Visualize Three-Dimensional Patient-Specific Models by a Mobile Head-Mounted Display.

INTRODUCTION: With the availability of low-cost head-mounted displays (HMDs), virtual reality environments (VREs) are increasingly being used in medicine for teaching and clinical purposes. Our aim was to develop an interactive, user-friendly VRE for tridimensional visualization of patient-specific organs, establishing a workflow to transfer 3-dimensional (3D) models from imaging datasets to our immersive VRE. MATERIALS AND METHODS: This original VRE model was built using open-source software and a mobile HMD, Samsung Gear VR. For its validation, we enrolled 33 volunteers: morphologists (n = 11), trainee surgeons (n = 15), and expert surgeons (n = 7). They tried our VRE and then filled in an original 5-point Likert-type scale 6-item questionnaire, considering the following parameters: ease of use, anatomy comprehension compared with 2D radiological imaging, explanation of anatomical variations, explanation of surgical procedures, preoperative planning, and experience of gastrointestinal/neurological disorders. Results in the 3 groups were statistically compared using analysis of variance. RESULTS: Using cross-sectional medical imaging, the developed VRE allowed to visualize a 3D patient-specific abdominal scene in 1 hour. Overall, the 6 items were evaluated positively by all groups; only anatomy comprehension was statistically significant different among the 3 groups. CONCLUSIONS: Our approach, based on open-source software and mobile hardware, proved to be a valid and well-appreciated system to visualize 3D patient-specific models, paving the way for a potential new tool for teaching and preoperative planning.