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Simple Summary: Blood clots are formed when blood vessels are injured. They help stop bleeding and heal wounds, but can also cause serious problems if they block blood flow or break off and travel to other organs. This study investigates how blood clots differ in people with cancer compared to healthy or non-cancerous individuals. This study found that cancer patients have higher levels of histones in their blood, which make their clots stiffer and resistant to lysis. Further, clots formed in cancer patients have higher viscoelastic properties, and hence are harder to break down. These findings suggest that cancer patients have abnormal clotting properties that may increase their risk of developing thrombosis, and evaluating these properties can be helpful in detecting cancer. Background: Blood viscoelasticity and plasma protein levels can play an important role in the diagnosis and prognosis of cancer. However, the role of histones and DNA in modulating blood clot properties remains to be investigated. This study investigates the differences in blood viscoelasticity and plasma protein levels among cancer patients, individuals with other diseases, and healthy individuals. Methods: Blood samples were collected from 101 participants, including 45 cancer patients, 22 healthy individuals, and 34 individuals with other diseases. Rheological properties of clots formed in vitro by reconstituted elements of fibrinogen or plasma were analyzed with an Anton Paar Rheometer, USA. Plasma protein levels of D-dimer, TPA, EPCR, fibrinogen, and histone H3 were measured through ELISA. Blood clots were formed with or without DNA and histones (H3) by adding thrombin and calcium to plasma samples, and were evaluated for viscoelasticity, permeability, and degradation. Results: Cancer patients show higher blood viscoelasticity and plasma D-dimer levels compared to healthy individuals and individuals with other diseases. Our in vitro analysis showed that the addition of histone to the plasma results in a significant decrease in viscoelasticity and mean fiber thickness of the clot formed thereafter. In parallel studies, using plasma from patients, DNA and histones were detected in fibrin clots and were associated with less degradation by t-PA. Moreover, our results show that the presence of DNA and histones not only increases clots' permeability, but also makes them more prone to degradation. Conclusions: Plasma histones and DNA affect the structure of the clot formed and induce defective fibrinolysis. Moreover, the increased viscoelastic properties of plasma from cancer patients can be used as potential biomarkers in cancer prognosis. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with breast cancer frequently complaint from insomnia difficulties that can affect quality of life and cancer progression. Such difficulties may result from rest-activity (i.e., 24 h alternation of sleep and wake) rhythm alterations consistently reported in this pathology. Currently proposed approaches to counter insomnia difficulties in patients with breast cancer have positive effects only on sleep complaints and well-being. Moreover, such approaches may be difficult to implement shortly after chemotherapy. Innovatively, vestibular stimulation would be particularly suited to tackling insomnia symptoms in patients with breast cancer. Indeed, recent reports have shown that vestibular stimulation could improve rest-activity rhythm and sleep in healthy volunteers. This perspective paper aims to support the evidence of using vestibular stimulation to improve rest-activity rhythms and reduce insomnia symptoms in patients with BC, with beneficial effects on quality of life and, potentially, survival. Insomnia symptoms are common among patients with breast cancer (BC; 20–70%) and are predictors of cancer progression and quality of life. Studies have highlighted sleep structure modifications, including increased awakenings and reduced sleep efficiency and total sleep time. Such modifications may result from circadian rhythm alterations consistently reported in this pathology and known as carcinogenic factors, including lower melatonin levels, a flattened diurnal cortisol pattern, and lower rest-activity rhythm amplitude and robustness. Cognitive behavioral therapy and physical activity are the most commonly used non-pharmacological interventions to counter insomnia difficulties in patients with BC. However, their effects on sleep structure remain unclear. Moreover, such approaches may be difficult to implement shortly after chemotherapy. Innovatively, vestibular stimulation would be particularly suited to tackling insomnia symptoms. Indeed, recent reports have shown that vestibular stimulation could resynchronize circadian rhythms and improve deep sleep in healthy volunteers. Moreover, vestibular dysfunction has been reported following chemotherapy. This perspective paper aims to support the evidence of using galvanic vestibular stimulation to resynchronize circadian rhythms and reduce insomnia symptoms in patients with BC, with beneficial effects on quality of life and, potentially, survival. [ABSTRACT FROM AUTHOR]

Simple Summary: This review discusses the enzymatic processes governing the initial stages of the synthesis of glycerophospholipids (phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine) and triacylglycerol. The key enzymes analyzed include glycerol-3-phosphate acyltransferases (GPAT) and 1-acylglycerol-3-phosphate acyltransferases (AGPAT). Additionally, because most AGPATs have lysophospholipid acyltransferase (LPLAT) activity, enzymes involved in the Lands cycle with similar functions were also included. The review further explores the potential therapeutic implications of inhibiting these enzymes in the treatment of metabolic diseases and cancer. By elucidating the enzymatic pathways involved in lipid synthesis and their impact on various pathological conditions, the article contributes to the understanding of these processes and their potential as therapeutic targets. This review delves into the enzymatic processes governing the initial stages of glycerophospholipid (phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine) and triacylglycerol synthesis. The key enzymes under scrutiny include GPAT and AGPAT. Additionally, as most AGPATs exhibit LPLAT activity, enzymes participating in the Lands cycle with similar functions are also covered. The review begins by discussing the properties of these enzymes, emphasizing their specificity in enzymatic reactions, notably the incorporation of polyunsaturated fatty acids (PUFAs) such as arachidonic acid and docosahexaenoic acid (DHA) into phospholipids. The paper sheds light on the intricate involvement of these enzymes in various diseases, including obesity, insulin resistance, and cancer. To underscore the relevance of these enzymes in cancer processes, a bioinformatics analysis was conducted. The expression levels of the described enzymes were correlated with the overall survival of patients across 33 different types of cancer using the GEPIA portal. This review further explores the potential therapeutic implications of inhibiting these enzymes in the treatment of metabolic diseases and cancer. By elucidating the intricate enzymatic pathways involved in lipid synthesis and their impact on various pathological conditions, this paper contributes to a comprehensive understanding of these processes and their potential as therapeutic targets. [ABSTRACT FROM AUTHOR]

Simple Summary: In spontaneous tumor regression, tumors shrink and disappear without conventional treatments. This phenomenon challenges the view that cancer is an irreversible genetic disease and that the only treatment option is to kill cancer cells or surgically remove them. In tumor reversion, cancer cells have been shown to return to normal cells when they are transplanted into a normal cellular environment. Additionally, people consuming a Western diet ingest excessive amounts of dietary phosphate, and a dysregulated oversupply of phosphate can be transported into cells, stimulating the cellular growth that forms tumors. Based on reviewed evidence, this paper proposes that reducing excessive dietary phosphate potentially activates tumor regression and reversion, as components of cancer cells are self-digested. Furthermore, fevers and fasting-mimicking diets are associated with tumor regression, which also may be initiated by reduced phosphate intake. Studies are needed to test dietary phosphate reduction in tumor regression and reversion to improve cancer patient survival. Tumors that spontaneously shrink from unknown causes in tumor regression, and that return to normal cells in tumor reversion, are phenomena with the potential to contribute new knowledge and novel therapies for cancer patient survival. Tumorigenesis is associated with dysregulated phosphate metabolism and an increased transport of phosphate into tumor cells, potentially mediated by phosphate overload from excessive dietary phosphate intake, a significant problem in Western societies. This paper proposes that reduced dietary phosphate overload and reregulated phosphate metabolism may reverse an imbalance of kinases and phosphatases in cell signaling and cellular proliferation, thereby activating autophagy in tumor regression and reversion. Dietary phosphate can also be reduced by sickness-associated anorexia, fasting-mimicking diets, and other diets low in phosphate, all of which have been associated with tumor regression. Tumor reversion has also been demonstrated by transplanting cancer cells into a healthy microenvironment, plausibly associated with normal cellular phosphate concentrations. Evidence also suggests that the sequestration and containment of excessive phosphate within encapsulated tumors is protective in cancer patients, preventing the release of potentially lethal amounts of phosphate into the general circulation. Reducing dietary phosphate overload has the potential to provide a novel, safe, and effective reversion therapy for cancer patients, and further research is warranted. [ABSTRACT FROM AUTHOR]

Simple Summary: The use of pre-emptive and prophylactic tyrosine kinase inhibitors (TKIs) after allogeneic hematopoietic stem cell transplantation (Allo-SCT) remains highly heterogeneous and very little is known about the use of third generation TKIs in this context. In this paper, we analyze the feasibility of maintenance with ponatinib administered after Allo-SCT to prevent cytologic relapse in a population of 48 patients with Philadelphia-positive acute lymphoblastic leukemia undergoing transplant while in complete cytologic remission. Although with the caution of the retrospective data, our analysis supports the feasibility of a ponatinib maintenance strategy after Allo-SCT, resulting in a low rate of discontinuation due to toxicity and a high probability of survival and relapse-free survival, particularly in the prophylactic group. In the majority of cases where a daily dose of 45 mg was started a dose reduction to 30–15 mg/day was required, which may be the appropriate dose to balance efficacy and tolerability. The administration of TKIs after Allo-SCT in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) remains controversial, and the TKI approach (prophylactic, pre-emptive or salvage) is still heterogeneous in transplant centers. In this context, very little is known about the feasibility and safety of third-generation TKIs. In this paper, we analyze the efficacy and safety of ponatinib (PONA) administered after Allo-SCT to prevent cytologic relapse of Ph + ALL. This is a multicenter observational study including 48 patients (pts) with Ph + ALL (median age 49 years) who received PONA after Allo-SCT while in complete cytological remission (cCR); 26 (54%) had positive minimal residual disease (MRD pos) before Allo-SCT. PONA was administered after Allo-SCT prophylactically (starting with MRD neg) in 26 pts or pre-emptively (starting with MRD pos post-SCT and without hematological relapse) in 22 pts. Patients treated prophylactically with PONA started treatment earlier, at a median of 4.3 months (range 1.5–6) after Allo-SCT, than those treated pre-emptively, who started PONA at a median of 7.4 months (range 2–63) after Allo-SCT (p = 0.01). The median starting dose of PONA was 30 mg/day (range 15–45). A dose reduction was required in 10/48 (21%) of cases, but a permanent discontinuation of PONA, due to toxicity, was required in only 5/48 pts (10.5%). No deaths due to PONA-related adverse events (AEs) were reported. The median follow-up time after Allo-SCT was 34 months (range 7.7–118). At the last follow-up, the median duration of PONA therapy was 22 months (range 2–100). The 5-year OS and RFS after Allo-SCT were 92% and 71%, respectively. The 5-year RFS after Allo-SCT of pts who received PONA prophylaxis was 95%, and it was 57% for those who received PONA pre-emptively (log-rank p = 0.02). In conclusion, this multicenter analysis of 48 patients with Ph + ALL undergoing Allo-SCT while in CcR, although with the caution of the retrospective data, supports the feasibility of PONA maintenance strategy after Allo-SCT with a low rate of discontinuations (10.5%) due to PONA-related AE. [ABSTRACT FROM AUTHOR]

Simple Summary: Proton therapy allows for more effective organs at risk avoidance than photon radiotherapy, thus reducing both radiation-induced toxicity and second cancer risk. The aim of the present paper is to compare protons and photons outcomes in the context of oropharyngeal and nasopharyngeal cancer and provide an updated comprehensive overview of the most promising new approaches and methodologies for treating head and neck cancer with protons. The growing interest in proton therapy (PT) in recent decades is justified by the evidence that protons dose distribution allows maximal dose release at the tumor depth followed by sharp distal dose fall-off. But, in the holistic management of head and neck cancer (HNC), limiting the potential of PT to a mere dosimetric advantage appears reductive. Indeed, the precise targeting of PT may help evaluate the effectiveness of de-escalation strategies, especially for patients with human papillomavirus associated-oropharyngeal cancer (OPC) and nasopharyngeal cancer (NPC). Furthermore, PT could have potentially greater immunogenic effects than conventional photon therapy, possibly enhancing both the radiotherapy (RT) capability to activate anti-tumor immune response and the effectiveness of immunotherapy drugs. Based on these premises, the aim of the present paper is to conduct a narrative review reporting the safety and efficacy of PT compared to photon RT focusing on NPC and OPC. We also provide a snapshot of ongoing clinical trials comparing PT with photon RT for these two clinical scenarios. Finally, we discuss new insights that may further develop clinical research on PT for HNC. [ABSTRACT FROM AUTHOR]

Simple Summary: The primary risk regarding Helicobacter pylori infection is that it is associated with gastric cancer. The lack of eradication of Helicobacter pylori has led to an increase in the prevalence of gastric cancer. We examined the literature from the year 2024 related to the Helicobacter pylori/gastric cancer association. Immunological studies increased, but they did not convince in the study of this infection. Most of the examined studies address the clinical treatment of this bacterium. However, to the same extent, other studies have investigated genetically individualized treatment. If, until now, clinical treatments have not yet been able to eradicate this bacterium, we recommend genetically individualized treatment. Numerous studies have been performed on Helicobacter pylori infection because of the high death rate linked to this illness and gastric cancer. An update on the key developments in recent years in the investigation of Helicobacter pylori and gastric cancer is the goal of this review. Using the search term "Helicobacter pylori, gastric cancer", the PubMed database was searched. Only papers published in 2024 fulfilled the inclusion criteria. Because case report papers were not part of our investigation, they satisfied the exclusion criteria. Most of the research on the variable genes of Helicobacter pylori is guided by genetics to determine potential treatments. Studies on clinical treatments for the eradication of H. pylori with promising therapeutic options are needed. We found the fewest studies related to the immunopathology of H. pylori infection, which is still unknown. In conclusion, priority should be given to this kind of research. [ABSTRACT FROM AUTHOR]

Simple Summary: Melanoma, the deadliest skin cancer, is a focus of research worldwide. This malignancy has been demonstrated to evade the immune system through several escape mechanisms. Among these, melanoma-related Dendritic Cells (DCs) alterations, particularly within the Sentinel Lymph Node (SLN), seem to play a key role. In SLNs, melanoma-related factors create a tumor microenvironment capable of impairing the immune response, inducing tolerance to tumor antigens and thus favoring SLN early metastases. The present literature review describes the interactions between Langerhans Cell (LC), a particular DC subset, and melanoma, suggesting a new potential therapeutic target. Background. Langerhans cells (LCs) are professional Dendritic Cells (DCs) involved in immunoregulatory functions. At the skin level, LCs are immature. In response to tissue injuries, they migrate to regional Lymph Nodes (LNs), reaching a full maturation state. Then, they become effective antigen-presenting cells (APCs) that induce anti-cancer responses. Notably, melanoma patients present several DC alterations in the Sentinel Lymph Node (SLN), where primary antitumoral immunity is generated. LCs are the most represented DCs subset in melanoma SLNs and are expected to play a key role in the anti-melanoma response. With this paper, we aim to review the current knowledge and future perspectives regarding LCs and melanoma. Methods. A systematic review was carried out according to the PRISMA statement using the PubMed (MEDLINE) library from January 2004 to January 2024, searching for original studies discussing LC in melanoma. Results. The final synthesis included 15 articles. Several papers revealed significant LCs–melanoma interactions. Conclusions. Melanoma immune escape mechanisms include SLN LC alterations, favoring LN metastasis arrival/homing and melanoma proliferation. The SLN LCs of melanoma patients are defective but not irreversibly, and their function may be restored by appropriate stimuli. Thus, LCs represent a promising target for future immunotherapeutic strategies and cancer vaccines. [ABSTRACT FROM AUTHOR]

Simple Summary: A multidisciplinary group researched and defined criteria to describe a sarcoma specialist treatment center or network. The project is led by Sarcoma Patient Advocacy Global Network (SPAGN), involves patient groups from around the world and is supported by clinical specialists and leading researchers. The paper identifies Core Principles and Key Features which define a specialist center/network. They are supported by evidence and experience. A primary aim is that new patients and their families can identify a specialist center which can provide curative treatment. A secondary aim is that countries where specialist treatment is not yet available can identify what they have to achieve to meet that ambition. The Core Principles allow a center or network to attain accreditation as a Sarcoma Intelligent Specialist Network. The Key Features are more aspirational and are expressed in a way that allows local needs, legal considerations and budgetary pressures to be taken into account. This is the first time an expert multidisciplinary group has defined specialism in cancer treatment in a worldwide context. The management of sarcomas in specialist centers delivers significant benefits. In much of the world, specialists are not available, and the development of expertise is identified as a major need. However, the terms 'specialist' or 'expert' center are rarely defined. Our objective is to offer a definition for patient advocates and a tool for healthcare providers to underpin improving the care of people with sarcoma. SPAGN developed a discussion paper for a workshop at the SPAGN 2023 Conference, attended by 75 delegates. A presentation to the Connective Tissue Oncology Society (CTOS) and further discussion led to this paper. Core Principles were identified that underlie specialist sarcoma care. The primary Principle is the multi-disciplinary team discussing every patient, at first diagnosis and during treatment. Principles for optimal sarcoma management include accurate diagnosis followed by safe, high-quality treatment, with curative intent. These Principles are supplemented by Features describing areas of healthcare, professional involvement, and service provision and identifying further research and development needs. These allow for variations because of national or local policies and budgets. We propose the term 'Sarcoma Intelligent Specialist Network' to recognize expertise wherever it is found in the world. This provides a base for further discussion and local refinement. [ABSTRACT FROM AUTHOR]

Simple Summary: This position paper aims to address specific clinical questions regarding the use of cyclin-dependent kinase 4/6 inhibitors in elderly patients with early or advanced breast cancer. Its objectives are to delineate the current state of knowledge regarding the efficacy of these treatments in the elderly population and their tolerance profile, including the impact on quality of life, with a particular focus on the frailest subgroups, and to attempt to define the optimal treatment strategy for elderly and fragile patients (dosage and therapeutic sequence). Background: Breast cancer (BC) incidence increases with age, particularly in HR-positive/HER2-negative subtypes. Cyclin-dependent kinase 4 and 6 inhibitors (CDK 4/6is) alongside endocrine therapy (ET) have emerged as promising treatments for HR-positive/HER2-negative advanced and early BC. However, their efficacy, safety, and impact on quality of life (QoL) in older and frail patients remain underexplored. Methods: This position paper assesses the existing literature from 2015 to 2024, focusing on CDK4/6is use in patients aged 65 years and older with HR-positive/HER2-negative BC. Results: Our analysis methodically addresses critical questions regarding the utilization of CDK4/6is in the elderly BC patient population, organizing findings from the metastatic and adjuvant settings. In the metastatic setting, CDK4/6is significantly improve progression-free survival (PFS), paralleling benefits observed in younger patients, and suggest potential overall survival (OS) benefits, warranting further investigation. Despite an increased incidence of grade ≥ 3 adverse events (AEs), such as neutropenia and asthenia, CDK4/6is present a markedly lower toxicity profile compared to traditional chemotherapy, with manageable side effects. QoL analysis indicates that integrating CDK4/6is into treatment regimens does not significantly impact elderly BC patients' daily life and symptom management. Special attention is given to frail subgroups, and personalized approaches are recommended to balance efficacy and adverse effects, such as starting with ET alone and introducing CDK4/6is upon progression in patients with a low disease burden. Transitioning to the adjuvant setting, early results, particularly with abemaciclib, indicate positive effects on disease-free survival (DFS), emphasizing the need for continued analysis to validate these findings and assess long-term implications. However, data on older patients are insufficient to conclude whether they truly benefit from this treatment. Conclusion: Overall, CDK4/6is present a favorable benefit-risk profile in older BC patients, at least in advanced BC; however, further research is warranted to optimize treatment strategies and improve outcomes in this population [ABSTRACT FROM AUTHOR]

Simple Summary: This paper discusses the challenges in treating high-grade gliomas, particularly glioblastomas, which are aggressive brain tumors with high recurrence rates. It highlights the limitations of current diagnostic imaging modalities, such as gadolinium-based MRI, in accurately detecting tumor recurrence versus treatment-related changes. The paper explores the emerging role of positron emission tomography (PET) in glioma imaging, especially with the use of radiotracers like PSMA, which can help differentiate between tumor recurrence and treatment effects. Furthermore, the paper reviews the concept of theranostics, which integrates diagnostics and therapy, offering a targeted approach to glioma treatment. It discusses various radioligands, including PSMA, 213Bi-DOTA-substance P, 90Y-DOTATOC, 18F-FDOPA, p-[131I]-iodo-L-phenylalanine, and 18F-GE-180, which have shown promise in diagnosing and treating recurrent gliomas. The potential of theranostics to minimize systemic toxicity and improve treatment outcomes is emphasized. Moreover, the paper highlights the importance of considering quality-of-life (QOL) outcomes in glioma patients, as conventional treatments often have significant impacts on patients' well-being. While theranostics offers a personalized approach to treatment, its potential promise for functional outcomes and QOL needs further investigation. The paper suggests that future research should focus on understanding the broader implications of theranostics on patient well-being, incorporating factors such as demographics, tumor characteristics, and treatment-related effects into QOL assessments. Overall, the paper underscores the potential of theranostics to revolutionize glioma management and improve patient outcomes in the future. Gliomas represent the most commonly occurring tumors in the central nervous system and account for approximately 80% of all malignant primary brain tumors. With a high malignancy and recurrence risk, the prognosis of high-grade gliomas is poor, with a mean survival time of 12–18 months. While contrast-enhanced MRI serves as the standard diagnostic imaging modality for gliomas, it faces limitations in the evaluation of recurrent gliomas, failing to distinguish between treatment-related changes and tumor progression, and offers no direct therapeutic options. Recent advances in imaging modalities have attempted to address some of these limitations, including positron emission tomography (PET), which has demonstrated success in delineating tumor margins and guiding the treatment of recurrent gliomas. Additionally, with the advent of theranostics in nuclear medicine, PET tracers, when combined with therapeutic agents, have also evolved beyond a purely diagnostic modality, serving both diagnostic and therapeutic roles. This review will discuss the growing involvement of theranostics in diagnosing and treating recurrent gliomas and address the associated impact on quality of life and functional recovery. [ABSTRACT FROM AUTHOR]

Simple Summary: Accurately predicting survival in patients with cancer receiving palliative radiotherapy is important for clinical decision making in cancer care management and delivery. This remains a challenge due to the heterogeneity of cancer diagnoses and a wide variety of prognostic factors. This study aims to review the literature to identify prognostic factors for clinical use as well as prognostic tools available to clinicians treating this population of patients. Based on the literature, we formulated evidence-based recommendations for clinicians to implement into practice with the intention of improving prognostic accuracy and overall patient care. (1) Background: Prognostication in patients with cancer receiving palliative radiotherapy remains a challenge. To improve the process, we aim to identify prognostic factors in this population from the literature and offer evidence-based recommendations on prognostication in patients undergoing palliative radiotherapy for non-curable or advanced cancers. (2) Methods: A systematic review was performed on the medical literature from 2005 to 2023 to extract papers on the prognosis of palliative radiotherapy patients with advanced cancer. The initial selection was performed by at least two authors to determine study relevance to the target area. Studies were then classified based on type and evidence quality to determine final recommendations. (3) Results: The literature search returned 57 papers to be evaluated. Clinical and biological prognostic factors were identified from these papers to improve clinical decision making or construct prognostic models. Twenty prognostic models were identified for clinical use. There is moderate evidence supporting (i) evidence-based factors (patient, clinical, disease, and lab) in guiding decision making around palliative radiation; (ii) that certain biological factors are of importance; (iii) prognostication models in patients with advanced cancer; and that (iv) SBRT or re-irradiation use can be guided by predictions of survival by prognostic scores or clinicians. Patients with more favorable prognoses are generally better suited to SBRT or re-irradiation, and the use of prognostic models can aid in this decision making. (4) Conclusions: This evaluation has identified several factors or tools to aid in prognosis and clinical decision making. Future studies should aim to further validate these tools and factors in a clinical setting, including the leveraging of electronic medical records for data availability. To increase our understanding of how causal factors interact with palliative radiotherapy, future studies should also examine and include prediction of response to radiation as an outcome. [ABSTRACT FROM AUTHOR]

Simple Summary: In this review, first, the history of EUS-guided biliary drainage (EUS-BD) is summarized. In the following chapters controversies arising from various approaches and challenges in EUS-BD, EUS-guided gallbladder drainage (EUS-GBD) and alternatively performed procedures are discussed from different points of view on the background of the available evidence. In addition, for all topics arguments in favor and against the techniques are described and reflected. The topics include "Why do we need procedures other than ERCP?"; "Should EUS-BD and ERCP be performed by the same operator?"; rendezvous techniques, including "Should rendezvous be used first?" and "Which rendezvous route should be used?"; percutaneous transhepatic cholangiography and biliary drainage (PTBD); "Should PTBD and EUS-BD be performed by the same physician?"; "Do we need cystotomes?"; "Do we need bougies?"; "Are all EUS needles the same for EUS-BD?"; "Plastic or metal stents?"; and adverse events. In this 14th document in a series of papers entitled "Controversies in Endoscopic Ultrasound" we discuss various aspects of EUS-guided biliary drainage that are debated in the literature and in practice. Endoscopic retrograde cholangiography is still the reference technique for therapeutic biliary access, but EUS-guided techniques for biliary access and drainage have developed into safe and highly effective alternative options. However, EUS-guided biliary drainage techniques are technically demanding procedures for which few training models are currently available. Different access routes require modifications to the basic technique and specific instruments. In experienced hands, percutaneous transhepatic cholangiodrainage is also a good alternative. Therefore, in this paper, we compare arguments for different options of biliary drainage and different technical modifications. [ABSTRACT FROM AUTHOR]

Simple Summary: Recent advancements in cancer research have proven immunotherapies to be a promising strategy for the treatment of hematological malignancies. The bispecific antibody (BsAb) format was developed to overcome the issues of monoclonal antibody-based therapies. T-cell engagers (TCEs) are BsAbs, which directly activate T-cells and their anti-tumor features, ultimately resulting in the lysis of the targeted tumor cells. In 2014, the FDA approved blinatumomab for treatment of acute lymphoblastic leukemia. As of November 2023, seven clinically approved TCE therapies are on the market. In this paper, we summarized the technical basis of the TCE technology, its application in hematology, and its current issues and prospects. Recent advancements in cancer immunotherapy have made directing the cellular immune response onto cancer cells a promising strategy for the treatment of hematological malignancies. The introduction of monoclonal antibody-based (mAbs) targeted therapy has significantly improved the prognosis for hematological patients. Facing the issues of mAb-based therapies, a novel bispecific antibody (BsAb) format was developed. T-cell engagers (TCEs) are BsAbs, which simultaneously target tumor-associated antigens on tumor cells and CD3 molecules present on T-cells. This mechanism allows for the direct activation of T-cells and their anti-tumor features, ultimately resulting in the lysis of tumor cells. In 2014, the FDA approved blinatumomab, a TCE directed to CD3 and CD19 for treatment of acute lymphoblastic leukemia. Since then, numerous TCEs have been developed, allowing for treating different hematological malignancies such as acute myeloid leukemia, multiple myeloma, and non-Hodgkin lymphoma and Hodgkin lymphoma. As of November 2023, seven clinically approved TCE therapies are on the market. TCE-based therapies still have their limitations; however, improving the properties of TCEs, as well as combining TCE-based therapies with other forms of treatment, give hope to find the cures for currently terminal diseases. In this paper, we summarized the technical basis of the TCE technology, its application in hematology, and its current issues and prospects. [ABSTRACT FROM AUTHOR]

Simple Summary: Immune checkpoint inhibitors have revolutionized cancer therapy and improved clinical outcomes. Immunotherapy is now increasingly combined with chemotherapy and other conventional treatments, such as radiation therapy, as part of the multimodal treatment of earlier-stage cancers. Although generally well tolerated and capable of inducing long-lasting responses, immunotherapy for thymic epithelial tumors can be challenging due to defects in immune self-tolerance, which increase the risk of immune-mediated toxicity. In order to improve the safety of immunotherapy and maximize clinical benefit in patients with thymic cancers, there is a pressing need to identify potential biomarkers of response and toxicity for this patient population. In this paper, we review the current role of immunotherapy for thymic cancers and discuss future applications across the spectrum of stage and histology of these diseases. Thymic epithelial tumors are a histologically diverse group of cancers arising from the epithelial compartment of the thymus. These tumors are characterized by a low tumor mutation burden, a lack of actionable genomic changes, and, especially with thymomas, defects in immune tolerance. Surgery is the mainstay of the management of resectable disease, whereas advanced, unresectable tumors are treated with platinum-based chemotherapy. Disease recurrence can occur months to years after frontline treatment. Although several options are available for conventional treatment of recurrent thymic tumors, response rates are generally low, and treatment-related toxicity can affect quality of life. A subset of patients benefit from biologic therapies, but there remains an unmet need for the development of new treatments. Immune checkpoint inhibitors are safe, clinically active, and have contributed to an improvement in survival for patients with a wide variety of cancers. However, the application of these revolutionary treatments for thymic cancers is limited to their use for the management of recurrent thymic carcinoma because of the risk of immune toxicity. In this paper, we review the current uses of immunotherapy for the management of thymic epithelial tumors and highlight potential strategies to improve safety and broaden the application of these treatments for patients with thymic cancers. [ABSTRACT FROM AUTHOR]

Simple Summary: Bladder cancer is a common disease in urological patients. The approach to treatment depends on the severity of the tumor; in this article, we focus on tumors that do not invade the muscle layer of the bladder. Those tumors are resected during an endoscopic procedure (TURBT), but often reoccur. Treating bladder cancer with drugs instead of surgical removal of the bladder (radical cystectomy) is paramount for patients quality of life and overall well-being. The aim of this paper is to review methods of conservative treatment of tumors unresponsive to the typical treatment of choice (BCG instillations). Bladder cancer is the 10th most popular cancer in the world, and non-muscle-invasive bladder cancer (NMIBC) is diagnosed in ~80% of all cases. Treatments for NMIBC include transurethral resection of the bladder tumor (TURBT) and intravesical instillations of Bacillus Calmette-Guérin (BCG). Treatment of BCG-unresponsive tumors is scarce and usually leads to Radical Cystectomy. In this paper, we review recent advancements in conservative treatment of BCG-unresponsive tumors. The main focus of the paper is FDA-approved medications: Pembrolizumab and Nadofaragene Firadenovec (Adstiladrin). Other, less researched therapeutic possibilities are also included, namely: N-803 immunotherapy, TAR-200 and TAR-210 intravesical delivery systems and combined Cabazitaxel, Gemcitabine and Cisplatin chemotherapy. Conservative treatment and delaying radical cystectomy would greatly benefit patients' quality of life; it is undoubtedly the future of BCG-unresponsive NMIBC. [ABSTRACT FROM AUTHOR]

Simple Summary: Much research has been conducted on the causes of childhood cancer, but many areas of uncertainty remain. We conducted a detailed search of recent studies investigating the causes of childhood cancer. Our findings, based on publications from 2014 to 2021, are summarized by topic in three separate papers: factors acting during childhood (Paper 1), factors relating to the parents and pregnancy (Paper 2), and factors relating to the environment (Paper 3). In this first paper, we summarize convincing evidence from studies that show increased childhood cancer risk associated with genetic cancer predisposition, birth defects, prior cancer, medical ionizing radiation, organ transplantation and exposure to cancer-causing viruses, and a reduced risk associated with some childhood vaccinations. Other factors discussed in this paper include the impact of the child's diet, allergies, medications, and body mass index. This review of factors associated with childhood cancer may help evidence-based efforts to reduce cancer in our pediatric populations. Purpose: To review the childhood risk factors for pediatric cancer (diagnosis before age 20). Methods: We conducted literature searches using Ovid Medline and Scopus to find primary research studies, review articles, and meta-analyses published from 2014 to 3 March 2021. Results: Strong evidence indicates that an array of genetic and epigenetic phenomena, structural birth defects, and chromosomal anomalies are associated with an increased risk of various childhood cancers. Increased risk is also associated with prior cancer, likely due to previous treatment agents and therapeutic ionizing radiation. Convincing evidence supports associations between several pediatric cancers and ionizing radiation, immunosuppression, and carcinogenic virus infection both in healthy children and in association with immune suppression following organ transplantation. Breastfeeding and a childhood diet rich in fruits and vegetables appears to reduce the risk of pediatric leukemia but the evidence is less strong. Childhood vaccination against carcinogenic viruses is associated with a lower risk of several cancers; there is less strong evidence that other childhood vaccinations more broadly may also lower risk. Ultraviolet (UV) radiation is associated with increased melanoma risk, although most melanomas following childhood UV exposure occur later, in adulthood. Evidence is weak or conflicting for the role of body mass index, other childhood infections, allergies, and certain treatments, including immunomodulator medications and human growth therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Metformin is one of the most widely used drugs in the world, since its first use in the second part of the 1950s in France (Aron, 1957) and in the United Kingdom (Rona, 1958), and is on the World Health Organization's List of Essential Medicines. Traditionally, metformin is used in diabetes mellitus, mainly in overweight and obese subjects, but also in other conditions of impaired glucose metabolism, such as insulin resistance. In recent years, in vitro and in vivo data on this molecule as an antiproliferative modulator have suggested a series of clinical trials in several tumors that—at the moment—have not confirmed the expected positive results. The aim of this paper is to offer a double vision of this molecule, with a very light side about the metabolic aspects and a darker side concerning its antineoplastic activity, focusing on molecular and subcellular pathways involved in both fields and discussing the contrast between preliminary cellular data and real clinical outcomes in different neoplasms. The ancient Roman god Ianus was a mysterious divinity with two opposite faces, one looking at the past and the other looking to the future. Likewise, metformin is an "old" drug, with one side looking at the metabolic role and the other looking at the anti-proliferative mechanism; therefore, it represents a typical and ideal bridge between diabetes and cancer. Metformin (1,1-dimethylbiguanidine hydrochloride) is a drug that has long been in use for the treatment of type 2 diabetes mellitus, but recently evidence is growing about its potential use in other metabolic conditions and in proliferative-associated diseases. The aim of this paper is to retrace, from a historical perspective, the knowledge of this molecule, shedding light on the subcellular mechanisms of action involved in metabolism as well as cellular and tissue growth. The intra-tumoral pharmacodynamic effects of metformin and its possible role in the management of different neoplasms are evaluated and debated. The etymology of the name Ianus is probably from the Latin term ianua, which means door. How many new doors will this old drug be able to open? [ABSTRACT FROM AUTHOR]

Simple Summary: Among the various options for urinary diversion following radical cystectomy, the orthotopic neobladder most closely resembles the original bladder both in location and function. However, a significant number of patients with these reservoirs have dysfunctional voiding. Our objective here is to provide the first systematic review focusing on the urodynamic and continence outcomes of ileal orthotopic neobladders. By summarising these important outcomes, the current paper may represent the reference manuscript for outcome comparison in future papers. The manuscript also describes the methodology of the urodynamic evaluation of the neobladders, highlighting the frequent lack of precise indications, accurate guidelines (at the state of the art, the same parameters used for the native bladder are also used for the ileal neobladders), standardised definitions, and standard values for outcome comparison. By underlining these gaps, our systematic review may aid future studies in having more adequate designs and will allow for a more accurate functional evaluation of the patients harbouring an ileal neobladder. Introduction: The orthotopic neobladder is the type of urinary diversion (UD) that most closely resembles the original bladder. However, in the literature the urodynamic aspects are scarcely analysed. Objective: To provide the first systematic review (SR) on the urodynamic (UDS) outcomes of the ileal orthotopic neobladders (ONB). Continence outcomes are also presented. Methods: A PubMed, Embase and Cochrane CENTRAL search for peer-reviewed studies on ONB published between January 2001–December 2022 was performed according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Results and Conclusion: Fifty-nine manuscripts were eligible for inclusion in this SR. A great heterogeneity of data was encountered. Concerning UDS parameters, the pooled mean was 406.2 mL (95% CI: 378.9–433.4 mL) for maximal (entero)cystometric capacity (MCC) and 21.4 cmH2O (95% CI: 17.5–25.4 cmH2O) for Pressure ONB at MCC. Postvoid-residual ranged between 4.9 and 101.6 mL. The 12-mo rates of day and night-time continence were 84.2% (95% CI: 78.7–89.1%) and 61.7% (95% CI: 51.9–71.1%), respectively.Despite data heterogeneity, the ileal ONB seems to guarantee UDS parameters that resemble those of the native bladder. Although acceptable rates of daytime continence are reported the issue of high rates of night-time incontinence remains unsolved. Adequately designed prospective trials adopting standardised postoperative care, terminology and methods of outcome evaluation as well as of conduction of the UDS in the setting of ONB are necessary to obtain homogeneous follow-up data and to establish UDS guidelines for this setting. [ABSTRACT FROM AUTHOR]

Simple Summary: This review begins by exploring the escalating global population of cancer survivors, drawing inspiration from Dr. Lidia Schapira's Keynote Conference on Survivorship 1.0 and Survivorship 2.0 Programs. It presents and discusses the transformed and constantly evolving landscape of cancer care, emphasizing patient-centric strategies within Cancer Survivorship Programs, including connection, support, and education. While spotlighting cancer recurrence surveillance, concerns arise regarding potential oversights in addressing the enduring mental and physical health impacts. The study further navigates mental health challenges faced by survivors providing strategies to mitigate them, insights into promising research areas, such as Precision Medicine's role in de-escalating oncology therapies, as well as advocating for early cancer awareness and referrals to supportive services. Dr. Schapira's insights also extend to examining online resources, emphasizing their role in educating healthcare practitioners and future generations in cancer care. Additionally, the paper aims to identify knowledge gaps in cancer care and envision future developments toward accurate, holistic care, improving survivor quality of life, and enhancing mental and physical well-being. The constantly escalating population of cancer survivors worldwide has prompted a focused exploration of their unique needs and experiences within the context of healthcare medicine. This review initiates its analysis inspired by Dr. Lidia Schapira's insightful keynote conference on the Survivorship 1.0 and Survivorship 2.0 Programs, shedding light on their implementation challenges and setting the stage for a comprehensive analysis of cancer survivorship initiatives. Within the transformed landscape of cancer care, patient-centric strategies embedded in cancer survivorship programs comprising vital elements such as connection, support, and education are presented. While placing cancer recurrence surveillance at the forefront, the review underlines concern regarding the potential oversight of the enduring impact on mental and physical health. Dr. Schapira's insights further extend into the exploration of mental health challenges faced by survivors, promoting an examination of diverse strategies to address these concerns. Furthermore, the discussion continues toward promising areas of research, notably Precision Medicine's role in de-escalating cancer therapies, and advocates for measures such as early cancer awareness and timely referrals to supportive services. Highlighting the significance of education, the role of online resources in enhancing the knowledge of healthcare practitioners and future generations in cancer care is then explored. The paper concludes by presenting some of the most prominent global current survivorship programs, identifying critical knowledge gaps in cancer care and projecting future developments aimed at delivering accurate and holistic care, improving the quality of life for survivors, and enhancing both mental and physical well-being. Drawing upon the insights from Dr. Schapira, this review lays the groundwork for a nuanced exploration of cancer survivorship and its multifaceted implications. [ABSTRACT FROM AUTHOR]

Simple Summary: Acute promyelocytic leukemia (APL) stands as a remarkable success in achieving high cure rates with chemotherapy-free treatment regimens. Despite these remarkable outcomes, hematologists managing patients with APL take into consideration the distinct side effects associated with the two dual differentiation agents, i.e., all-transretinoic acid (ATRA) and arsenic trioxide (ATO). The objective of this paper is to review relevant literature data and discuss the recommended management strategies of non-hematologic early and late complications that arosein patients diagnosed with APL who were treated with ATO and ATRA-based regimens. The hallmark of acute promyelocytic leukemia (APL) is the presence of the characteristic fusion transcript of the promyelocytic leukemia gene with the retinoic acid receptor α gene (PML::RARA). The PML::RARA fusion is a molecular target for all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). Therapies based on ATRA plus ATO have excellent outcomes in terms of complete remission rates, overall survival, and achievement of deep and durable molecular responses with a very low incidence of relapse. However, although the combination of ATRA and ATO has lower hematologic toxicity than standard chemotherapy, its use is associated with a spectrum of distinctive toxicities, such as differentiation syndrome, liver toxicity, QT interval prolongation, and neurotoxicity. Rigorous monitoring of patients' clinical evolution is indispensable for identifying and addressing each complication. The objective is to maintain an equilibrium between treatment-induced adverse events and therapeutic efficacy. This paper focused on non-hematologic complications associated with the combination of ATRA and ATO. Additionally, we discuss late-onset complications of this therapy. In summary, the majority of treatment-related adverse events are manageable, self-limiting, and reversible. More so, there seems to be a lower incidence rate of secondary neoplasms compared to standard chemotherapy. However, further research is required to assess how the ATRA plus ATO regimen affects the emergence of additional comorbidities. [ABSTRACT FROM AUTHOR]

Simple Summary: Neurofibromatosis Type 1 is an inherited tumour predisposition syndrome with a varied clinical phenotype. Long-term monitoring through imaging is inconsistent and varies in high- and low-income countries. Implementation of a clinical practice guideline through a multidisciplinary clinic is instrumental to the care of adult Neurofibromatosis Type 1 patients. This systematic review aims to evaluate the association between a country's socioeconomic status and diagnostic modalities and strategies used for adult Neurofibromatosis Type 1 patients. Our results show multiple imaging modalities are used in high-income countries; however, there is limited use in low-income countries. The two most common diagnostic modalities used in developed countries are WB MRI and FDG PET/CT. Background: Neurofibromatosis Type 1 is an autosomal dominant tumour-predisposition condition commonly diagnosed in childhood and fully penetrant by adulthood. Long-term monitoring through imaging is inconsistent and varies between high- and low-income countries. Implementation of a clinical practice guideline through a multidisciplinary clinic is instrumental to the care of adult Neurofibromatosis Type 1 patients. We aim to systematically review international diagnostic modalities and strategies to evaluate any association between a country's socioeconomic status and diagnostic modalities or strategies used for Neurofibromatosis Type 1 patients. Methods: We searched PubMed, Embase, Web of Science, and Cochrane. Relevant clinical information on the surveillance of adult Neurofibromatosis Type 1 patients worldwide was reviewed, extracted, and synthesised. Results: We identified 51 papers reporting on 7724 individuals. Multiple imaging modalities are actively employed in high-income and upper-middle-income countries for surveying adult Neurofibromatosis Type 1 patients. We did not find any relevant papers from low- and middle-income countries. Conclusions: This systematic review suggests that there is robust data on diagnostic modalities for adult Neurofibromatosis Type 1 patients in high-income countries, but not for low- and middle-income countries. There is a lack of data on consolidated diagnostic strategies from both high- and low-income countries. Efforts should be made to publish data on usual clinical practice in low- and middle-income countries to develop clinical practice guidelines describing best medical practice to fit a local context. [ABSTRACT FROM AUTHOR]

Simple Summary: This paper presents a novel approach to produce virtual contrast enhanced (VCE) images for nasopharyngeal cancer (NPC) without the use of contrast agents, which carry certain risks. This model uses pixelwise gradient term to capture the shape and a GAN terms to capture the texture of the real contrast enhanced T1C images With similar accuracy to existing models, our method shows an advantage in reproducing texture closer to the realistic contrast-enhanced images. This results are tested by various measures, including mean absolute error (MAE), mean square error (MSE) and structural similarity index (SSIM) for similarity accuracy; total mean square variation per mean intensity (TMSVPMI), the total absolute vari-ation per mean intensity (TAVPMI), Tenengrad function per mean intensity (TFPMI) and variance function per mean intensity (VFPMI) Various variations of the model, including fine-tuning of the hyperparameters, normalization methods on the images and using single modality, have also been investigated to test the optimal performance. Background: The development of advanced computational models for medical imaging is crucial for improving diagnostic accuracy in healthcare. This paper introduces a novel approach for virtual contrast enhancement (VCE) in magnetic resonance imaging (MRI), particularly focusing on nasopharyngeal cancer (NPC). Methods: The proposed model, Pixelwise Gradient Model with GAN for Virtual Contrast Enhancement (PGMGVCE), makes use of pixelwise gradient methods with Generative Adversarial Networks (GANs) to enhance T1-weighted (T1-w) and T2-weighted (T2-w) MRI images. This approach combines the benefits of both modalities to simulate the effects of gadolinium-based contrast agents, thereby reducing associated risks. Various modifications of PGMGVCE, including changing hyperparameters, using normalization methods (z-score, Sigmoid and Tanh) and training the model with T1-w or T2-w images only, were tested to optimize the model's performance. Results: PGMGVCE demonstrated a similar accuracy to the existing model in terms of mean absolute error (MAE) (8.56 ± 0.45 for Li's model; 8.72 ± 0.48 for PGMGVCE), mean square error (MSE) (12.43 ± 0.67 for Li's model; 12.81 ± 0.73 for PGMGVCE) and structural similarity index (SSIM) (0.71 ± 0.08 for Li's model; 0.73 ± 0.12 for PGMGVCE). However, it showed improvements in texture representation, as indicated by total mean square variation per mean intensity (TMSVPMI) (0.124 ± 0.022 for ground truth; 0.079 ± 0.024 for Li's model; 0.120 ± 0.027 for PGMGVCE), total absolute variation per mean intensity (TAVPMI) (0.159 ± 0.031 for ground truth; 0.100 ± 0.032 for Li's model; 0.153 ± 0.029 for PGMGVCE), Tenengrad function per mean intensity (TFPMI) (1.222 ± 0.241 for ground truth; 0.981 ± 0.213 for Li's model; 1.194 ± 0.223 for PGMGVCE) and variance function per mean intensity (VFPMI) (0.0811 ± 0.005 for ground truth; 0.0667   ± 0.006 for Li's model; 0.0761   ± 0.006 for PGMGVCE). Conclusions: PGMGVCE presents an innovative and safe approach to VCE in MRI, demonstrating the power of deep learning in enhancing medical imaging. This model paves the way for more accurate and risk-free diagnostic tools in medical imaging. [ABSTRACT FROM AUTHOR]

Simple Summary: The increased detection of pancreatic cysts in recent years has triggered extensive diagnostic investigations to clarify their potential risk of malignancy, resulting in a large number of patients undergoing numerous imaging follow-up studies for many years. Therefore, there is a growing need for optimization of the current surveillance protocol to provide a practical and reasonable solution in the face of an ever-growing demand. The aim of this paper is to discuss the current available evidence on whether the implementation of unenhanced abbreviated-MRI (A-MRI) protocols for cystic pancreatic lesion surveillance could improve healthcare economics and reduce waiting lists in clinical practice without significantly reducing diagnostic accuracy. The increased detection of pancreatic cysts in recent years has triggered extensive diagnostic investigations to clarify their potential risk of malignancy, resulting in a large number of patients undergoing numerous imaging follow-up studies for many years. Therefore, there is a growing need for optimization of the current surveillance protocol to reduce both healthcare costs and waiting lists, while still maintaining appropriate sensibility and specificity. Imaging is an essential tool for evaluating patients with intraductal papillary mucinous neoplasms (IPMNs) since it can assess several predictors for malignancy and thus guide further management recommendations. Although contrast-enhanced magnetic resonance imaging (MRI) with magnetic resonance cholangiopancreatography (MRCP) has been widely recommended by most international guidelines, recent results support the use of unenhanced abbreviated-MRI (A-MRI) protocols as a surveillance tool in patients with IPMN. In fact, A-MRI has shown high diagnostic performance in malignant detection, with high sensitivity and specificity as well as excellent interobserver agreement. The aim of this paper is, therefore, to discuss the current available evidence on whether the implementation of an abbreviated-MRI (A-MRI) protocol for cystic pancreatic lesion surveillance could improve healthcare economics and reduce waiting lists in clinical practice without significantly reducing diagnostic accuracy. [ABSTRACT FROM AUTHOR]

Simple Summary: The main topic of this present paper is an analysis of the performance of FAPi agents in cases of thyroid cancer, both in diagnosis and therapy. Up to 50% of instances of thyroid cancer lose their avidity to 131I and become more aggressive. In this scenario, [18F]FDG PET/CT is used for evaluating the widespread nature of the disease, despite its low sensitivity. FAPi agents represent a promising novel class of tracers and a valid alternative to [18F]FDG and 131I scans. They also represent a thriving future perspective in theranostics. This systematic review aims to examine and discuss the advantages and pitfalls of FAPi agents presented in the literature in the context of the diagnosis and treatment of thyroid cancer. (1) Background: Thyroid cancer (TC) is often treated with surgery followed by iodine-131. Up to 50% of the instances of TC lose their avidity to 131I, becoming more aggressive. In this scenario, [18F]FDG PET/CT imaging is used for evaluating the widespread nature of the disease, despite its low sensitivity and a false negative rate of 8–21.1%. A novel class of PET agents targeting the fibroblast activation protein inhibitor (FAPi) has emerged, studied particularly for their potential application to theranostics. (2) Methods: A search of the literature was performed by two independent authors (P.G. and L.E.) using the PubMed, Scopus, Web of Science, Cochrane Library, and EMBASE databases. The following terms were used: "FAP" or "FAPi" or "Fibroblast activating protein" and "thyroid" or "thyroid cancer", in different combinations. The included papers were original articles, clinical studies, and case reports in the English language. No time limits were used. Editorials, conference papers, reviews, and preclinical studies were excluded. (3) Results: There were 31 papers that were selected. Some studies reported a low or absent FAPi uptake in TC lesions; others reported promising findings for the detection of metastases. (4) Conclusions: The preliminary results are encouraging. FAPI agents are an alternative to [18F]FDG and a promising theranostic tool. However, further studies with a larger population are needed. [ABSTRACT FROM AUTHOR]

Simple Summary: Constant technological development of modern imaging has led to substantial improvement in management and decision-making in the diagnostic and prognostic process of many different neoplasms. This also applies to cervical cancer. The main evidence, providing the base of recently updated ESGO-ESTRO-ESP recommendations (2023) on the management and treatment of cervical cancer, has been evaluated and reviewed in this paper. Ultrasound has been suggested as a valid alternative to MRI in primary diagnostic workup of cervical cancer if performed by an expert sonographer. Additionally, CT or PET/CT exhibits a substantial role in assessing the extrapelvic spread of the disease in locally advanced cases or when suspicious lymph nodes are detected. The purpose of this article is to provide a comprehensive review of the role of different imaging techniques in staging settings, displaying a focused interest in the use of ultrasound. Following the European Society of Gynaecological Oncology (ESGO), the European Society for Radiotherapy and Oncology (ESTRO), and the European Society of Pathology (ESP) joint guidelines (2018) for the management of patients with cervical cancer, treatment decisions should be guided by modern imaging techniques. After five years (2023), an update of the ESGO-ESTRO-ESP recommendations was performed, further confirming this statement. Transvaginal/transrectal ultrasound (TRS/TVS) or pelvic magnetic resonance (MRI) enables tumor delineation and precise assessment of its local extent, including the evaluation of the depth of infiltration in the bladder- or rectal wall. Additionally, both techniques have very high specificity to confirm the presence of metastatic pelvic lymph nodes but fail to exclude them due to insufficient sensitivity to detect small-volume metastases, as in any other currently available imaging modality. In early-stage disease (T1a to T2a1, except T1b3) with negative lymph nodes on TVS/TRS or MRI, surgicopathological staging should be performed. In all other situations, contrast-enhanced computed tomography (CECT) or 18F-fluorodeoxyglucose positron emission tomography combined with CT (PET-CT) is recommended to assess extrapelvic spread. This paper aims to review the evidence supporting the implementation of diagnostic imaging with a focus on ultrasound at primary diagnostic workup of cervical cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: This research studied how three types of proteins, called interleukins (namely 8, 17A and 33), are present in the blood of healthy people and people with colon cancer. Colon cancer is a disease that affects the large intestine. The paper looked at 82 people, 42 of whom had colon cancer and 40 of whom did not. The researchers divided the cancer patients into four groups based on how severe their cancer was. The study measured the amount of interleukins in the blood of each person using a special test. The paper analyzed the results of the test, considering the age, gender, and cancer stage of each person. The results showed that younger people, and those with less severe cancer had more interleukins in their blood. The paper also found that two of the interleukins (8 and 17A) were higher in the cancer group, while one of them (33) was higher in the healthy group. The study also found that the interleukins were related to each other in both groups. This research concluded that the interleukins might help detect colon cancer and predict how it will progress. This paper could help improve the diagnosis and treatment of colon cancer. This research investigated the serum levels of three interleukins (IL8, IL17A, and IL33) and the possible relationships between them in healthy people and colon cancer patients at different stages. This study involved 82 participants, 42 of whom had colon cancer and 40 were healthy individuals. The cancer patients were classified into four groups according to the TNM staging classification of colon and rectal cancer. Serum levels of the interleukins were measured by the ELISA test. The data were analyzed statistically to compare the demographic characteristics, the interleukin levels across cancer stages, and the correlation between interleukins in both groups. The results showed that women had more early-stage colon cancer diagnoses, while men had more advanced-stage cancer diagnoses. Stage two colon cancer was more common in older people. Younger people, men, and those with early-stage colon cancer had higher levels of interleukins. The levels of IL8 and IL17A were higher in the cancer group, while the level of IL33 was higher in the healthy group. There was a strong correlation between IL8 and IL17A levels in both groups (p = 0.001). IL17A influenced the level of IL33 in the cancer group (p = 0.007). This study suggested that cytokine variation profiles could be useful for detecting colon cancer and predicting its outcome. [ABSTRACT FROM AUTHOR]

Simple Summary: Biliary tract malignancies, including cholangiocarcinoma (CCA) and gallbladder neoplasms, present intricate challenges in diagnosis and treatment. This comprehensive overview highlights the diversity of CCA subtypes, their genetic underpinnings, and the pivotal role of etiological factors. Despite diagnostic complexities, advancements in genomic sequencing reveal promising therapeutic targets, such as FGFR2 alterations and IDH1 mutations. Dr. James Cleary's insights underscore the potential of these targets in reshaping the treatment landscape. This paper provides insights into the conventional understanding of biliary tract malignancies and emphasizes the critical need for ongoing research to optimize outcomes in this challenging cancer subtype. By elucidating diverse FGFR2 alterations and the potential of IDH1 inhibition, the aim is to pave the way for targeted therapeutic interventions. As we delve deeper into understanding the intricate complexities of biliary tract malignancies, this research seeks to drive precision medicine forward, offering hope for improved treatment strategies and outcomes in the face of this formidable cancer. This paper provides insights into the conventional understanding of biliary tract malignancies, with a specific focus on cholangiocarcinoma (CCA). We then delve into the groundbreaking ideas presented by Dr. James Cleary. CCA, originating from biliary tree cells, manifests diverse subtypes contingent upon anatomical localization and differentiation status. These variants exhibit discrete genetic aberrations, yielding disparate clinical phenotypes and therapeutic modalities. Intrahepatic, perihilar, and distal CCAs intricately involve distinct segments of the biliary tree, further categorized as well-differentiated, moderately differentiated, or poorly differentiated adenocarcinomas based on their histological differentiation. Understanding the etiological factors contributing to CCA development assumes paramount importance. Stratifying these factors into two groups, those unrelated to fluke infestations (e.g., viral hepatitis and fatty liver conditions) and those associated with fluke infestations (e.g., chronic liver inflammation), facilitates predictive modeling. The epidemiology of CCA exhibits global variability, with Southeast Asia notably displaying higher incidences attributed primarily to liver fluke infestations. Jaundice resulting from bile duct obstruction constitutes a prevalent clinical manifestation of CCA, alongside symptoms like malaise, weight loss, and abdominal pain. Diagnostic challenges arise due to the symptomatic overlap with other biliary disorders. Employing comprehensive liver function tests and imaging modalities such as computed tomography assumes a pivotal role in ensuring accurate diagnosis and staging. However, the definitive confirmation of CCA necessitates a biopsy. Treatment modalities, predominantly encompassing surgical resection and radiation therapy, hold curative potential, although a considerable subset of patients is deemed unresectable upon exploration. Challenges intensify, particularly in cases classified as cancer of unknown origin, underscoring the imperative for early intervention. Advancements in genomic sequencing have revolutionized precision medicine in CCA. Distinct genomic markers, including fibroblast growth factor receptor 2 (FGFR2) alterations and isocitrate dehydrogenase 1 (IDH1) mutations, have emerged as promising therapeutic targets. FGFR2 alterations, encompassing mutations and rearrangements, play pivotal roles in oncogenesis, with FGFR inhibitors demonstrating promise despite identified resistance mechanisms. Similarly, IDH1 inhibitors face challenges with resistance, despite encouraging early clinical trial results, prompting exploration of novel irreversible inhibitors. Dr. James Cleary's illuminating discourse underscores the significance of diverse FGFR2 alterations and the potential of IDH1 inhibition in reshaping the treatment landscape for CCA. These findings unveil critical avenues for targeted therapeutic interventions, emphasizing the critical need for ongoing research to optimize outcomes in this challenging cancer subtype, incorporating innovative insights from Dr. Cleary. [ABSTRACT FROM AUTHOR]

Simple Summary: This paper delves into the latest developments in the emerging therapies for cholangiocarcinoma, with a focus on precision medicine, immunotherapy, and targeted therapies. We explore the potential of genomic profiling to tailor treatments to individual patients, as well as the promising results of immunotherapeutic agents in clinical trials. Furthermore, we examine the role of specific molecular targets and their inhibitors in slowing disease progression. The findings discussed in this paper offer hope for improved outcomes and prolonged survival in cholangiocarcinoma patients using more effective and personalized treatment strategies. Cholangiocarcinoma is a heterogeneous group of biliary tract cancers that has a poor prognosis and globally increasing incidence and mortality. While surgical resection remains the only curative option for the treatment of cholangiocarcinoma, the majority of cancers are unresectable at the time of diagnosis. Additionally, the prognosis of cholangiocarcinoma remains poor even with the current first-line systemic therapy regimens, highlighting the difficulty of treating locally advanced, metastatic, or unresectable cholangiocarcinoma. Through recent developments, targetable oncogenic driver mutations have been identified in the pathogenesis of cholangiocarcinoma, leading to the utilization of molecular targeted therapeutics. In this review, we comprehensively discuss the latest molecular therapeutics for the treatment of cholangiocarcinoma, including emerging immunotherapies, highlighting promising developments and strategies. [ABSTRACT FROM AUTHOR]

Simple Summary: The current approach to breast cancer screening, which is based on a person's age, overlooks individual-level differences in breast cancer risk. As a result, many people are over- or under-screened according to their actual risk of breast cancer. Risk-stratified breast screening may overcome the limitations of age-based screening, but there are still many knowledge gaps regarding how best to implement it in the population setting. This study will generate the first Canadian evidence on the adoption of breast cancer risk assessment in the population setting, to support the future implementation of risk-stratified breast cancer screening. This study demonstrated that, while risk assessment for risk-stratified screening at the population level is feasible, an equity lens must be considered in implementation to ensure cancer-screening disparities are not widened. Risk-stratified breast screening has been proposed as a strategy to overcome the limitations of age-based screening. A prospective cohort study was undertaken within the PERSPECTIVE I&I project, which will generate the first Canadian evidence on multifactorial breast cancer risk assessment in the population setting to inform the implementation of risk-stratified screening. Recruited females aged 40–69 unaffected by breast cancer, with a previous mammogram, underwent multifactorial breast cancer risk assessment. The adoption of multifactorial risk assessment, the effectiveness of methods for collecting risk factor information and the costs of risk assessment were examined. Associations between participant characteristics and study sites, as well as data collection methods, were assessed using logistic regression; all p-values are two-sided. Of the 4246 participants recruited, 88.4% completed a risk assessment, with 79.8%, 15.7% and 4.4% estimated at average, higher than average and high risk, respectively. The total per-participant cost for risk assessment was CAD 315. Participants who chose to provide risk factor information on paper/telephone (27.2%) vs. online were more likely to be older (p = 0.021), not born in Canada (p = 0.043), visible minorities (p = 0.01) and have a lower attained education (p < 0.0001) and perceived fair/poor health (p < 0.001). The 34.4% of participants requiring risk factor verification for missing/unusual values were more likely to be visible minorities (p = 0.009) and have a lower attained education (p ≤ 0.006). This study demonstrates the feasibility of risk assessment for risk-stratified screening at the population level. Implementation should incorporate an equity lens to ensure cancer-screening disparities are not widened. [ABSTRACT FROM AUTHOR]

Simple Summary: The diagnosis of oral cancer can require multiple biopsies to increase the likelihood of sampling the most pathologic site within a lesion. Optical coherence tomography (OCT) enables the examination of subsurface morphology and has shown potential in biopsy guidance. OCT captures changes in tissue stratification related to depth, topology, and presence of the epithelial-stromal boundary, which are structural biomarkers for pre-invasive and invasive oral cancer. This study presents a neural network pipeline to simplify OCT interpretation by providing information about epithelial depth and stratification through simple en face maps. U-net models were employed to segment the boundaries of the epithelial layer, and supporting convolutional neural networks were used for identification of the imaging field and artifacts. Non-cancerous, precancerous, and cancerous pathologies across the oral cavity were evaluated. The predictions demonstrate as-good-as or better agreement than inter-rater agreement, suggesting strong predictive power. This paper aims to simplify the application of optical coherence tomography (OCT) for the examination of subsurface morphology in the oral cavity and reduce barriers towards the adoption of OCT as a biopsy guidance device. The aim of this work was to develop automated software tools for the simplified analysis of the large volume of data collected during OCT. Imaging and corresponding histopathology were acquired in-clinic using a wide-field endoscopic OCT system. An annotated dataset (n = 294 images) from 60 patients (34 male and 26 female) was assembled to train four unique neural networks. A deep learning pipeline was built using convolutional and modified u-net models to detect the imaging field of view (network 1), detect artifacts (network 2), identify the tissue surface (network 3), and identify the presence and location of the epithelial–stromal boundary (network 4). The area under the curve of the image and artifact detection networks was 1.00 and 0.94, respectively. The Dice similarity score for the surface and epithelial–stromal boundary segmentation networks was 0.98 and 0.83, respectively. Deep learning (DL) techniques can identify the location and variations in the epithelial surface and epithelial–stromal boundary in OCT images of the oral mucosa. Segmentation results can be synthesized into accessible en face maps to allow easier visualization of changes. [ABSTRACT FROM AUTHOR]

Simple Summary: This study explores cryopreservation thyroid autotransplantation as an alternative to hormonal replacement therapy for patients who underwent thyroidectomy during childhood or adulthood. The research evaluates the impact of modern cryopreservation techniques on follicular cell integrity through a feasibility study and literature review. Results indicate preserved tissue architecture and cell viability. Animal and human studies demonstrate successful transplantation outcomes. However, long-term follow-up data are lacking. The findings suggest promising viability of cryopreserved thyroid tissue, yet further research is needed to assess hormone secretion and ensure sustained functionality. This alternative therapy could offer tailored hormone production, aligning with physiological needs. Background and aims: This paper aims to study an alternative solution to hormonal replacement therapy in specific groups of patients who underwent thyroidectomy during childhood or adulthood. After cryopreservation, thyroid autotransplantation could be an alternative solution which would allow us to use the ability of the thyroid tissue of producing hormones according to the physiological needs of the body. Materials and methods: A feasibility study about the effects of the most modern cryopreservation techniques on the structural and functional integrity of the follicular cells of the thyroid tissue has been carried out. Patients who could benefit from the treatment have been found for both autotransplant techniques. Additionally, a literature review has been conducted. Results: The histological analysis has shown that cryopreservation does not alter the original architecture, and the culture examination that cell viability is successfully preserved. Moreover, both thyroid autotransplantation studies on animals and those on humans that were found in the literature have shown good results regarding the viability and functionality of the transplant. Conclusions: The viability of cryopreserved thyroid tissue found in this study is encouraging. Further studies to evaluate the levels of FT3, FT4 and thyroglobulin in thyroid tissue after cryopreservation are needed to verify that the secretory properties of the thyrocytes have been maintained intact. Furthermore, autotransplanted cases found in the literature do not have a long-term follow-up. [ABSTRACT FROM AUTHOR]

Simple Summary: Pencil beam scanning nozzles monitor the beam position in real time and record the results in log files. We cannot, however, place a beam position monitor at the isocenter during treatment, so accurate online beam position corrections and log file analyses rely on an algorithm to project the beam position from the nozzle to the isocentric plane. We present four generic algorithms and determined the accuracy of each approach in three example configurations and two nozzle lengths. Beam position uncertainties along the beam trajectory arise from the accelerator, beamline, and scanning magnets (SMs). They can be monitored in real time, e.g., through strip ionization chambers (ICs), and treatments can be paused if needed. Delivery is more reliable and accurate if the beam position is projected from monitored nozzle parameters to the isocenter, allowing for accurate online corrections to be performed. Beam position projection algorithms are also used in post-delivery log file analyses. In this paper, we investigate the four potential algorithms that can be applied to all pencil beam scanning (PBS) nozzles. For some combinations of nozzle configurations and algorithms, however, the projection uses beam properties determined offline (e.g., through beam tuning or technical commissioning). The best algorithm minimizes either the total uncertainty (i.e., offline and online) or the total offline uncertainty in the projection. Four beam position algorithms are analyzed (A1–A4). Two nozzle lengths are used as examples: a large nozzle (1.5 m length) and a small nozzle (0.4 m length). Three nozzle configurations are considered: IC after SM, IC before SM, and ICs on both sides. Default uncertainties are selected for ion chamber measurements, nozzle entrance beam position and angle, and scanning magnet angle. The results for other uncertainties can be determined by scaling these results or repeating the error propagation. We show the propagation of errors from two locations and the SM angle to the isocenter for all the algorithms. The best choice of algorithm depends on the nozzle length and is A1 and A3 for the large and small nozzles, respectively. If the total offline uncertainty is to be minimized (a better choice if the offline uncertainty is not stable), the best choice of algorithm changes to A1 for the small nozzle for some hardware configurations. Reducing the nozzle length can help to reduce the gantry size and make proton therapy more accessible. This work is important for designing smaller nozzles and, consequently, smaller gantries. This work is also important for log file analyses. [ABSTRACT FROM AUTHOR]

Simple Summary: Immunotherapeutic synergy represents the cornerstone of the treatment intended for patients with clear-cell renal-cell carcinoma. In most cases, this type of cancer manifests its first symptoms at an advanced stage, thus compromising the use of local therapies such as surgery. This paper aims to describe immune checkpoint proteins, known to suppress an anti-cancer immune response, as well as their inhibitors. Interleukin-2, a cytokine used as a therapeutic option and implicated in the activation of the immune cells, is also discussed. This review further emphasizes the role of the immunotherapeutic combination, not only as an alternative to current treatments devised to counteract the progression and metastasis of ccRCC but also as a valid solution aimed at alleviating the limitations resulting from immune-based monotherapies. Clear-cell Renal-Cell Carcinoma (ccRCC) is the most common type of renal-cell carcinoma (RCC). In many cases, RCC patients manifest the first symptoms during the advanced stage of the disease. For this reason, immunotherapy appears to be one of the dominant treatments to achieve a resolution. In this review, we focus on the presentation of the main immune checkpoint proteins that act as negative regulators of immune responses, such as PD-1, CTLA-4, LAG-3, TIGIT, and TIM-3, and their respective inhibitors. Interleukin-2, another potential component of the treatment of ccRCC patients, has also been covered. The synergy between several immunotherapies is one of the main aspects that unites the conclusions of research in recent years. To date, the combination of several immunotherapies enhances the efficacy of a monotherapy, which often manifests important limitations. Immunotherapy aimed at restoring the anti-cancer immune response in ccRCC, involved in the recognition and elimination of cancer cells, may also be a valid solution for many other types of immunogenic tumors that are diagnosed in the final stages. [ABSTRACT FROM AUTHOR]

Simple Summary: In our paper, we examine various facets of prostate cancer lung metastasis. We explore their clinical manifestations, such as respiratory symptoms and potential complications. Diagnostic modalities, including imaging techniques and biomarker analysis, are scrutinized for accurate identification. Treatment strategies, encompassing surgery, radiation therapy, chemotherapy, and targeted therapies, are discussed for their efficacy. Survival outcomes are assessed to gauge the effectiveness of different interventions. Through comprehensive analysis, we aim to provide insights into managing prostate cancer lung metastasis and enhancing patient care and outcomes. Prostate cancer lung metastasis represents a clinical conundrum due to its implications for advanced disease progression and the complexities it introduces in treatment planning. As the disease progresses to distant sites such as the lung, the clinical management becomes increasingly intricate, requiring tailored therapeutic strategies to address the unique characteristics of metastatic lesions. This review seeks to synthesize the current state of knowledge surrounding prostate cancer metastasis to the lung, shedding light on the diverse array of clinical presentations encountered, ranging from subtle radiological findings to overt symptomatic manifestations. By examining the diagnostic modalities utilized in identifying this metastasis, including advanced imaging techniques and histopathological analyses, this review aims to provide insights into the diagnostic landscape and the challenges associated with accurately characterizing lung metastatic lesions in prostate cancer patients. Moreover, this review delves into the nuances of therapeutic interventions employed in managing prostate cancer lung metastasis, encompassing systemic treatments such as hormonal therapies and chemotherapy, as well as metastasis-directed therapies including surgery and radiotherapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Risk assessment in early breast cancer is critical for clinical decisions, but defining risk categories poses a significant challenge. The integration of conventional histopathology and biomarkers with artificial intelligence (AI) techniques, including machine learning and deep learning, has the potential to offer more precise information. AI applications extend beyond detection to histological subtyping, grading, and molecular feature identification. The successful integration of AI into clinical practice requires collaboration between histopathologists, molecular pathologists, computational pathologists, and oncologists to optimize patient outcomes. Effective risk assessment in early breast cancer is essential for informed clinical decision-making, yet consensus on defining risk categories remains challenging. This paper explores evolving approaches in risk stratification, encompassing histopathological, immunohistochemical, and molecular biomarkers alongside cutting-edge artificial intelligence (AI) techniques. Leveraging machine learning, deep learning, and convolutional neural networks, AI is reshaping predictive algorithms for recurrence risk, thereby revolutionizing diagnostic accuracy and treatment planning. Beyond detection, AI applications extend to histological subtyping, grading, lymph node assessment, and molecular feature identification, fostering personalized therapy decisions. With rising cancer rates, it is crucial to implement AI to accelerate breakthroughs in clinical practice, benefiting both patients and healthcare providers. However, it is important to recognize that while AI offers powerful automation and analysis tools, it lacks the nuanced understanding, clinical context, and ethical considerations inherent to human pathologists in patient care. Hence, the successful integration of AI into clinical practice demands collaborative efforts between medical experts and computational pathologists to optimize patient outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Proton therapy is a crucial tool for head and neck and skull-base cancers, offering benefits over photon therapy by lowering the risk of adverse effects. However, its full potential could be further explored by better characterizing the uncertainties related to its relative biological effectiveness. Addressing these uncertainties is crucial for maximizing the potential of proton therapy. We explore the significance of proton therapy's biological impact in these cancers, review relative biological effectiveness uncertainties and modeling, and examine clinical outcomes and evidence linking specific biological factors to patient adverse effects. Additionally, we review the current clinical practices and provide insights into innovative developments and their future clinical implementation. Proton therapy has emerged as a crucial tool in the treatment of head and neck and skull-base cancers, offering advantages over photon therapy in terms of decreasing integral dose and reducing acute and late toxicities, such as dysgeusia, feeding tube dependence, xerostomia, secondary malignancies, and neurocognitive dysfunction. Despite its benefits in dose distribution and biological effectiveness, the application of proton therapy is challenged by uncertainties in its relative biological effectiveness (RBE). Overcoming the challenges related to RBE is key to fully realizing proton therapy's potential, which extends beyond its physical dosimetric properties when compared with photon-based therapies. In this paper, we discuss the clinical significance of RBE within treatment volumes and adjacent serial organs at risk in the management of head and neck and skull-base tumors. We review proton RBE uncertainties and its modeling and explore clinical outcomes. Additionally, we highlight technological advancements and innovations in plan optimization and treatment delivery, including linear energy transfer/RBE optimizations and the development of spot-scanning proton arc therapy. These advancements show promise in harnessing the full capabilities of proton therapy from an academic standpoint, further technological innovations and clinical outcome studies, however, are needed for their integration into routine clinical practice. [ABSTRACT FROM AUTHOR]

Simple Summary: Ultrasonography is a basic tool used in the evaluation of thyroid nodules, but there is no single feature of this method which predicts malignancy with statistical significance. The aim of the study is to assess the usefulness of contrast enhanced-ultrasound (CEUS) in the differential diagnosis of thyroid nodules. The highest value of the study results from the multiparameter approach to the evaluation of thyroid lesions in the light of new diagnostics methods and assessment of the unique combinations of both B-mode and CEUS features as predictors of thyroid cancers. Moreover, several qualitative contrast features predicting benign lesions were evaluated. The preliminary results indicate that CEUS is a useful tool in assessing the risk of malignancy of thyroid lesions. The combination of the qualitative enhancement parameters and B-mode sonographic features significantly increases the method's usefulness. Further studies should be performed to introduce CEUS patterns in the diagnostic algorithm of thyroid nodules. Background: Ultrasonography is a primary method used in the evaluation of thyroid nodules, but no single feature of this method predicts malignancy with high accuracy. Therefore, this paper aims to assess the utility of contrast-enhanced ultrasound (CEUS) in the differential diagnosis of thyroid nodules. Methods: The study group comprised 188 adult patients (155 women and 33 men) who preoperatively underwent CEUS of a thyroid nodule classified as Bethesda categories II–VI after fine-needle aspiration biopsy. During the CEUS examination, 1.5 mL of SonoVue contrast was injected intravenously, after which 15 qualitative CEUS enhancement patterns were analysed. Results: The histopathologic results comprised 65 benign thyroid nodules and 123 thyroid carcinomas. The dominant malignant CEUS features, such as hypo- and heterogeneous enhancement and slow wash-in phase, were evaluated, whereas high enhancement, ring enhancement, and a slow wash-out phase were assessed as predictors of benign lesions. Two significant combinations of B-mode and CEUS patterns were noted, namely, hypoechogenicity with heterogeneous enhancement and non-smooth margins with hypo- or iso-enhancement. Conclusions: The preliminary results indicate that CEUS is a useful tool in assessing the risk of malignancy of thyroid lesions. The combination of the qualitative enhancement parameters and B-mode sonographic features significantly increases the method's usefulness. [ABSTRACT FROM AUTHOR]

Simple Summary: Peritoneal disease in gastric cancer has a poor prognosis, with a median survival of 3–6 months and a 5-year survival rate of 0%. Despite multiple advancements in therapeutics, the National Comprehensive Cancer Network (NCCN) guidelines recommend systemic chemotherapy or best supportive care for GC with peritoneal dissemination. According to several studies, CRS + HIPEC could provide survival advantages in gastric cancer peritoneal metastasis compared to pSC. Background: Peritoneal carcinomatosis is one of deadliest metastatic patterns of gastric cancer, being associated with a median overall survival (OS) of 4 months. Up to now, palliative systemic chemotherapy (pSC) has been the only recommended treatment. The aim of this study is to evaluate a potential survival benefit after CRS + HIPEC compared to pSC. Methods: A systematic review was conducted according to the PRISMA guidelines in March 2024. Manuscripts reporting patients with peritoneal carcinomatosis from gastric cancer treated with CRS + HIPEC were included. A meta-analysis was performed, comparing the survival results between the CRS + HIPEC and pSC groups, and the primary outcome was the comparison in terms of OS. We performed random-effects meta-analysis of odds ratios (ORs). We assessed heterogeneity using the Q2 statistic. Results: Out of the 24 papers included, 1369 patients underwent CRS + HIPEC, with a median OS range of 9.8–28.2 months; and 103 patients underwent pSC, with a median OS range of 4.9–8 months. CRS + HIPEC was associated with significantly increased survival compared to palliative systemic chemotherapy (−1.8954 (95% CI: −2.5761 to −1.2146; p < 0.001). Conclusions: CRS + HIPEC could provide survival advantages in gastric cancer peritoneal metastasis compared to pSC. [ABSTRACT FROM AUTHOR]

Simple Summary: Among head–neck tumors, squamous cell carcinoma is the most frequent histotype and includes a range of malignancies with different sites of origin as well as different therapeutic strategies and clinical outcomes. In daily practice, patients with head–neck squamous cell carcinoma are seen in various clinical settings, requiring a multidisciplinary approach to therapeutic decisions and clinical care. 18F-FDG PET/CT plays a well-defined role in the management of these tumors for pre-treatment staging and radiotherapy planning as well as treatment-response assessment and post-therapy follow-up. This paper is an overview of the standard use of 18F-FDG PET/CT in the various clinical scenarios of head–neck squamous cell carcinoma. Also, emerging applications will be reviewed, including the use of radiopharmaceuticals other than 18F-FDG, PET/MRI implementation in clinical practice, and the use of radiomics and machine learning. This article provides an overview of the use of 18F-FDG PET/CT in various clinical scenarios of head–neck squamous cell carcinoma, ranging from initial staging to treatment-response assessment, and post-therapy follow-up, with a focus on the current evidence, debated issues, and innovative applications. Methodological aspects and the most frequent pitfalls in head–neck imaging interpretation are described. In the initial work-up, 18F-FDG PET/CT is recommended in patients with metastatic cervical lymphadenectomy and occult primary tumor; moreover, it is a well-established imaging tool for detecting cervical nodal involvement, distant metastases, and synchronous primary tumors. Various 18F-FDG pre-treatment parameters show prognostic value in terms of disease progression and overall survival. In this scenario, an emerging role is played by radiomics and machine learning. For radiation-treatment planning, 18F-FDG PET/CT provides an accurate delineation of target volumes and treatment adaptation. Due to its high negative predictive value, 18F-FDG PET/CT, performed at least 12 weeks after the completion of chemoradiotherapy, can prevent unnecessary neck dissections. In addition to radiomics and machine learning, emerging applications include PET/MRI, which combines the high soft-tissue contrast of MRI with the metabolic information of PET, and the use of PET radiopharmaceuticals other than 18F-FDG, which can answer specific clinical needs. [ABSTRACT FROM AUTHOR]

Simple Summary: Endometrial cancer is the sixth most common cancer among women worldwide, with an increasing mortality rate. The standard treatment of patients with advanced or recurrent endometrial cancer has not changed significantly in recent decades. However, in recent years, immunotherapy has emerged as a promising strategy that harnesses the body's immune system against cancer, particularly in advanced or recurrent cases, offering patients the possibility of better results and longer survival. Our critical review analyses recent findings in the literature in this field, focusing on the role of immunotherapy in the treatment of this disease. In particular, it focuses on the importance of molecular biology and highlights how this can change the choice of treatment, providing insights for future therapeutic strategies. The Cancer Genome Atlas (TCGA) has radically changed the history of endometrial cancer by outlining a new classification, based on its molecular characteristics. In the field of oncology, we are approaching the new era of molecular biology, particularly regarding endometrial cancer, with the increasing importance of targeted therapy. This paper is a review of phase III randomized controlled trials published in English between January 2019 and December 2023, comparing drugs of interest with standard adjuvant treatment and molecular subtypes in endometrial cancer. The use of immunotherapy alone or in combination with chemotherapy as therapy in patients with recurrent or advanced primary or metastatic endometrial cancer significantly improves the prognosis of these patients. The results show greater efficacy of all proposed treatments for mismatch repair deficiency (dMMR/MSI-H) patients compared to mismatch repair proficiency (pMMR) patients. Progression-free survival (PFS) and overall survival (OS) are better in dMMR patients in all studies analysed. Immunotherapy has the potential to revolutionize the gynaecological cancer treatment landscape, offering a new pathway and new hope for endometrial cancer patients, improving their outcomes in the future. Given the exciting results obtained in dMMR/MSI-H patients, MMR status should be investigated in every patient with advanced endometrial cancer at the time of diagnosis. [ABSTRACT FROM AUTHOR]

Simple Summary: The role of neurogenic locus notch homolog protein 1 (NOTCH1)- and nuclear factor erythroid 2-related factor 2 (NRF2)-related pathways is highly heterogeneous in small cell lung cancer (SCLC) and, when they are both abnormally activated, they can synergistically cause neoplastic proliferation. In this paper, we investigate the possible role of KEAP1 silencing in NRF2 and NOTCH axis deregulation in SCLC by evaluating its impact on the modulation of cellular defense systems, cell growth, and differentiation. We also investigate the impact of these systems' impairment in response to conventional chemotherapies and NOTCH inhibitors in silenced SCLC cell lines with different Kelch-like ECH-associated protein 1 (KEAP1) alterations. The KEAP1/NRF2 pathway is a master regulator of several redox-sensitive genes implicated in the resistance of tumor cells against therapeutic drugs. The dysfunction of the KEAP1/NRF2 system has been correlated with neoplastic patients' outcomes and responses to conventional therapies. In lung tumors, the growth and the progression of cancer cells may also involve the intersection between the molecular NRF2/KEAP1 axis and other pathways, including NOTCH, with implications for antioxidant protection, survival of cancer cells, and drug resistance to therapies. At present, the data concerning the mechanism of aberrant NRF2/NOTCH crosstalk as well as its genetic and epigenetic basis in SCLC are incomplete. To better clarify this point and elucidate the contribution of NRF2/NOTCH crosstalk deregulation in tumorigenesis of SCLC, we investigated genetic and epigenetic dysfunctions of the KEAP1 gene in a subset of SCLC cell lines. Moreover, we assessed its impact on SCLC cells' response to conventional chemotherapies (etoposide, cisplatin, and their combination) and NOTCH inhibitor treatments using DAPT, a γ-secretase inhibitor (GSI). We demonstrated that the KEAP1/NRF2 axis is epigenetically controlled in SCLC cell lines and that silencing of KEAP1 by siRNA induced the upregulation of NRF2 with a consequent increase in SCLC cells' chemoresistance under cisplatin and etoposide treatment. Moreover, KEAP1 modulation also interfered with NOTCH1, HES1, and DLL3 transcription. Our preliminary data provide new insights about the downstream effects of KEAP1 dysfunction on NRF2 and NOTCH deregulation in this type of tumor and corroborate the hypothesis of a cooperation of these two pathways in the tumorigenesis of SCLC. [ABSTRACT FROM AUTHOR]

Simple Summary: A large body of multidisciplinary evidence involves the topic of thyroid cancer (the most common endocrine malignancy). Nevertheless, exceptional findings such as thyroid cancer in ectopic thyroid tissue, representing 0.3–0.5% of the malignant neoplasia with any location, suggest even greater challenges. Awareness remains the key operative element since the index of suspicion is low, especially in non-cervical areas. Hence, currently, the ectopic thyroid remains a matter of individualized management. The ectopic mediastinal thyroid (EMT) is part of the less frequent sublingual ectopic sites. Here, we introduce the most complex analysis in published EMT data (N = 117 patients) that identified an unexpectedly high rate of malignancy (18.8%), papillary cancer being the most frequent histological type. A rate of 5.98% amid all EMTs represented individuals confirmed with unrelated (non-thyroid) malignancies. Thyroid anomalies (other than EMT presence) were reported in 38.33% of the benign EMT, while the overall malignancy rate in EMTs was higher than expected according to prior data when compared to other ectopic sites. We aimed to analyze the management of the ectopic mediastinal thyroid (EMT) with respect to EMT-related cancer and non-malignant findings related to the pathological report, clinical presentation, imaging traits, endocrine profile, connective tissue to the cervical (eutopic) thyroid gland, biopsy or fine needle aspiration (FNA) results, surgical techniques and post-operatory outcome. This was a comprehensive review based on revising any type of freely PubMed-accessible English, full-length original papers including the keywords "ectopic thyroid" and "mediastinum" from inception until March 2024. We included 89 original articles that specified EMTs data. We classified them into four main groups: (I) studies/case series (n = 10; N = 36 EMT patients); (II) malignant EMTs (N = 22 subjects; except for one newborn with immature teratoma in the EMT, only adults were reported; mean age of 62.94 years; ranges: 34 to 90 years; female to male ratio of 0.9). Histological analysis in adults showed the following: papillary (N = 11/21); follicular variant of the papillary type (N = 2/21); Hürthle cell thyroid follicular malignancy (N = 1/21); poorly differentiated (N = 1/21); anaplastic (N = 2/21); medullary (N = 1/21); lymphoma (N = 2/21); and MALT (mucosa-associated lymphoid tissue) (N = 1/21); (III) benign EMTs with no thyroid anomalies (N = 37 subjects; mean age of 56.32 years; ranges: 30 to 80 years; female to male ratio of 1.8); (IV) benign EMTs with thyroid anomalies (N = 23; female to male ratio of 5.6; average age of 52.1 years). This panel involved clinical/subclinical hypothyroidism (iatrogenic, congenital, thyroiditis-induced, and transitory type upon EMT removal); thyrotoxicosis (including autonomous activity in EMTs that suppressed eutopic gland); autoimmune thyroiditis/Graves's disease; nodules/multinodular goiter and cancer in eutopic thyroid or prior thyroidectomy (before EMT detection). We propose a 10-item algorithm that might help navigate through the EMT domain. To conclude, across this focused-sample analysis (to our knowledge, the largest of its kind) of EMTs, the EMT clinical index of suspicion remains low; a higher rate of cancer is reported than prior data (18.8%), incident imagery-based detection was found in 10–14% of the EMTs; surgery offered an overall good outcome. A wide range of imagery, biopsy/FNA and surgical procedures is part of an otherwise complex personalized management. [ABSTRACT FROM AUTHOR]

Simple Summary: Metastatic breast cancer is an aggressive disease that early diagnostic attempts is of an utmost importance. A machine learning model that utilizes NCA and MRMR in this work is attempting to isolate pertinent dysregulated miRNA's for the different four cancer stages. This work compares the current clinical diagnostic approaches with the proposed ML model results. Determining the tumor origin in humans is vital in clinical applications of molecular diagnostics. Metastatic cancer is usually a very aggressive disease with limited diagnostic procedures, despite the fact that many protocols have been evaluated for their effectiveness in prognostication. Research has shown that dysregulation in miRNAs (a class of non-coding, regulatory RNAs) is remarkably involved in oncogenic conditions. This research paper aims to develop a machine learning model that processes an array of miRNAs in 1097 metastatic tissue samples from patients who suffered from various stages of breast cancer. The suggested machine learning model is fed with miRNA quantitative read count data taken from The Cancer Genome Atlas Data Repository. Two main feature-selection techniques have been used, mainly Neighborhood Component Analysis and Minimum Redundancy Maximum Relevance, to identify the most discriminant and relevant miRNAs for their up-regulated and down-regulated states. These miRNAs are then validated as biological identifiers for each of the four cancer stages in breast tumors. Both machine learning algorithms yield performance scores that are significantly higher than the traditional fold-change approach, particularly in earlier stages of cancer, with Neighborhood Component Analysis and Minimum Redundancy Maximum Relevance achieving accuracy scores of up to 0.983 and 0.931, respectively, compared to 0.920 for the FC method. This study underscores the potential of advanced feature-selection methods in enhancing the accuracy of cancer stage identification, paving the way for improved diagnostic and therapeutic strategies in oncology. [ABSTRACT FROM AUTHOR]

Simple Summary: The microenvironment of hepatocellular carcinoma is a really complex milieu, containing a wide variety of cells with specific tasks, belonging to both the mesenchimal and immunitary systems, the extracellular matrix, growth factors, proinflammatory cytokines, and translocated bacterial products. This intricate environment represents a source of potential targets in order to establish a wide and multitask therapeutic strategy for hepatocellular carcinoma. Hepatocellular carcinoma is a malignant tumor that originates from hepatocytes in an inflammatory substrate due to different degrees of liver fibrosis up to cirrhosis. In recent years, there has been growing interest in the role played by the complex interrelationship between hepatocellular carcinoma and its microenvironment, capable of influencing tumourigenesis, neoplastic growth, and its progression or even inhibition. The microenvironment is made up of an intricate network of mesenchymal cells, immune system cells, extracellular matrix, and growth factors, as well as proinflammatory cytokines and translocated bacterial products coming from the intestinal microenvironment via the enterohepatic circulation. The aim of this paper is to review the role of the HCC microenvironment and describe the possible implications in the choice of the most appropriate therapeutic scheme in the prediction of tumor response or resistance to currently applied treatments and in the possible development of future therapeutic perspectives, in order to circumvent resistance and break down the tumor's defensive fort. [ABSTRACT FROM AUTHOR]

Simple Summary: In this paper, we look at the role of artificial intelligence (AI) advancements in prostate cancer diagnosis and management. Specifically, we focus on magnetic resonance prostate reconstruction, prostate cancer detection/stratification/reconstruction, positron emission tomography/computed tomography, androgen deprivation therapy, and prostate biopsy. A total of 64 studies were included. Our results showed that deep learning AI models in prostate cancer diagnosis show promise but are not yet ready for clinical use due to variability in methods, labels, and evaluation criteria. Conducting additional research while acknowledging the limitations is crucial for reinforcing the utility and effectiveness of AI-based models in clinical settings. Background: The aim was to analyze the current state of deep learning (DL)-based prostate cancer (PCa) diagnosis with a focus on magnetic resonance (MR) prostate reconstruction; PCa detection/stratification/reconstruction; positron emission tomography/computed tomography (PET/CT); androgen deprivation therapy (ADT); prostate biopsy; associated challenges and their clinical implications. Methods: A search of the PubMed database was conducted based on the inclusion and exclusion criteria for the use of DL methods within the abovementioned areas. Results: A total of 784 articles were found, of which, 64 were included. Reconstruction of the prostate, the detection and stratification of prostate cancer, the reconstruction of prostate cancer, and diagnosis on PET/CT, ADT, and biopsy were analyzed in 21, 22, 6, 7, 2, and 6 studies, respectively. Among studies describing DL use for MR-based purposes, datasets with magnetic field power of 3 T, 1.5 T, and 3/1.5 T were used in 18/19/5, 0/1/0, and 3/2/1 studies, respectively, of 6/7 studies analyzing DL for PET/CT diagnosis which used data from a single institution. Among the radiotracers, [68Ga]Ga-PSMA-11, [18F]DCFPyl, and [18F]PSMA-1007 were used in 5, 1, and 1 study, respectively. Only two studies that analyzed DL in the context of DT met the inclusion criteria. Both were performed with a single-institution dataset with only manual labeling of training data. Three studies, each analyzing DL for prostate biopsy, were performed with single- and multi-institutional datasets. TeUS, TRUS, and MRI were used as input modalities in two, three, and one study, respectively. Conclusion: DL models in prostate cancer diagnosis show promise but are not yet ready for clinical use due to variability in methods, labels, and evaluation criteria. Conducting additional research while acknowledging all the limitations outlined is crucial for reinforcing the utility and effectiveness of DL-based models in clinical settings. [ABSTRACT FROM AUTHOR]

Simple Summary: The 2021 WHO classification of central nervous system (CNS) tumors is challenging for neuroradiologists due to the central role of the molecular profile of tumors. We performed a scoping review of recent literature to assess the existing data on the power of novel data analysis tools to predict new tumor classes by imaging. We found room for performance improvement for subgroups with lower incidence (e.g., 1p/19q codeleted or IDH1/2 mutated gliomas) and patients with rare diagnoses (e.g., pediatric gliomas, midline gliomas). More data regarding functional MRI techniques need to be collected. Studies explicitly designed to assess the generalizability of AI-aided tools for predicting molecular tumor subgroups are lacking. The 2021 WHO classification of CNS tumors is a challenge for neuroradiologists due to the central role of the molecular profile of tumors. The potential of novel data analysis tools in neuroimaging must be harnessed to maintain its role in predicting tumor subgroups. We performed a scoping review to determine current evidence and research gaps. A comprehensive literature search was conducted regarding glioma subgroups according to the 2021 WHO classification and the use of MRI, radiomics, machine learning, and deep learning algorithms. Sixty-two original articles were included and analyzed by extracting data on the study design and results. Only 8% of the studies included pediatric patients. Low-grade gliomas and diffuse midline gliomas were represented in one-third of the research papers. Public datasets were utilized in 22% of the studies. Conventional imaging sequences prevailed; data on functional MRI (DWI, PWI, CEST, etc.) are underrepresented. Multiparametric MRI yielded the best prediction results. IDH mutation and 1p/19q codeletion status prediction remain in focus with limited data on other molecular subgroups. Reported AUC values range from 0.6 to 0.98. Studies designed to assess generalizability are scarce. Performance is worse for smaller subgroups (e.g., 1p/19q codeleted or IDH1/2 mutated gliomas). More high-quality study designs with diversity in the analyzed population and techniques are needed. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer is a leading cause of death worldwide. The costs involved in cancer diagnosis and treatment are extraordinary. Important steps that can be taken that would reduce costs include earlier cancer diagnosis for which significant headway is being made through biomarker identification in bodily fluids and imaging. Other important steps will be to identify treatment approaches that do not 'break the bank' and affect a patient's wellbeing. Herein, we aim to highlight the potential of phytochemicals as a cost-effective approach to aid in the treatment of cancer. We focus on phytochemicals that target ion channels, as molecules that mediate critical communication of a cell with its environment. Ultimately, we posit that phytochemicals targeting ion channels can be employed to aid cancer treatment. Modern chemotherapies offer a broad approach to cancer treatment but eliminate both cancer and non-cancer cells indiscriminately and, thus, are associated with a host of side effects. Advances in precision oncology have brought about new targeted therapeutics, albeit mostly limited to a subset of patients with an actionable mutation. They too come with side effects and, ultimately, 'self-resistance' to the treatment. There is recent interest in the modulation of ion channels, transmembrane proteins that regulate the flow of electrically charged molecules in and out of cells, as an approach to aid treatment of cancer. Phytochemicals have been shown to act on ion channels with high specificity regardless of the tumor's genetic profile. This paper explores the use of phytochemicals in cancer symptom management and treatment. [ABSTRACT FROM AUTHOR]