Search Results (26,425)

Solid tumors of the cervicothoracic junction, the posterior mediastinum, or bilateral dorsal thoracic tumors represent a challenge in pediatric surgical oncology. The aim of this study was to evaluate trap-door thoracotomy and clamshell thoracotomy as surgical approaches. A single-center retrospective study of children with solid tumors in these specific localizations was performed. From 2015 to 2023, 26 children (17 girls; 9 boys) were treated at a median age of 54 months (range 8–229). Tumor resection was performed for neuroblastoma (n = 11); metastatic disease (n = 7); malignant rhabdoid tumor (n = 4); Ewing sarcoma (n = 1); inflammatory myofibroblastic tumor (n = 1); rhabdomyosarcoma (n = 1); and neurofibroma (n = 1). The surgical goal of macroscopic complete excision was achieved in all of the 14 children who underwent trap-door thoracotomy and in 11 of the 12 children who underwent clamshell thoracotomy. There were no major complications. At a median follow-up of 8 months (range 0–60), the disease was under local control or in complete remission in 66.7% of the children. In conclusion, surgical resection of solid tumors of the cervicothoracic junction in children can be performed safely and successfully with trap-door thoracotomy and with clamshell thoracotomy for posterior mediastinal or bilateral dorsal thoracic tumors. Full article

Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed at late stages, limiting treatment options and survival rates. Pyroptosis-related gene signatures hold promise as PDAC prognostic markers, but limited gene pools and small sample sizes hinder their utility. We aimed to enhance PDAC prognosis with a comprehensive multi-algorithm analysis. Using R, we employed natural language processing and latent Dirichlet allocation on PubMed publications to identify pyroptosis-related genes. We collected PDAC transcriptome data (n = 1273) from various databases, conducted a meta-analysis, and performed differential gene expression analysis on tumour and non-cancerous tissues. Cox and LASSO algorithms were used for survival modelling, resulting in a pyroptosis-related gene expression-based prognostic index. Laboratory and external validations were conducted. Bibliometric analysis revealed that pyroptosis publications focus on signalling pathways, disease correlation, and prognosis. We identified 357 pyroptosis-related genes, validating the significance of BHLHE40, IL18, BIRC3, and APOL1. Elevated expression of these genes strongly correlated with poor PDAC prognosis and guided treatment strategies. Our accessible nomogram model aids in PDAC prognosis and treatment decisions. We established an improved gene signature for pyroptosis-related genes, offering a novel model and nomogram for enhanced PDAC prognosis. Full article

The discovery of the distinctive structure of heavy chain-only antibodies in species belonging to the Camelidae family has elicited significant interest in their variable antigen binding domain (VHH) and gained attention for various applications, such as cancer diagnosis and treatment. This article presents an overview of the characteristics, advantages, and disadvantages of VHHs as compared to conventional antibodies, and their usage in diverse applications. The singular properties of VHHs are explained, and several strategies that can augment their utility are outlined. The preclinical studies illustrating the diagnostic and therapeutic efficacy of distinct VHHs in diverse formats against solid cancers are summarized, and an overview of the clinical trials assessing VHH-based agents in oncology is provided. These investigations demonstrate the enormous potential of VHHs for medical research and healthcare. Full article

Cutaneous squamous cell carcinoma (cSCC) is a very common skin malignancy with poor prognosis for patients with locally advanced or metastatic cSCC (mcSCC). PI3K/AKT/mTOR and cell cycle signalling pathways are often dysregulated in mcSCC. A combination drug approach has been theorised to overcome the underwhelming clinical performance of targeted inhibitors as single agents. This study investigates the potential of targeted inhibition of the p110α−subunit of PI3K with PIK−75 or BGT226 (P13Ki), and of CDK1/2/5/9 with dinaciclib (CDKi) as single agents and in combination. The patient−derived mcSCC cell lines, UW−CSCC1 and UW−CSCC2, were used to assess cell viability, migration, cell signalling, cell cycle distribution, and apoptosis. PIK−75, BGT226, and dinaciclib exhibited strong cytotoxic potency as single agents. Notably, the non−malignant HaCaT cell line was unaffected. In 2D cultures, PIK−75 synergistically enhanced the cytotoxic effects of dinaciclib in UW−CSCC2, but not UW−CSCC1. Interestingly, this pattern was reversed in 3D spheroid models. Despite the combination of PIK−75 and dinaciclib resulting in an increase in cell cycle arrest and apoptosis, and reduced cell motility, these differences were largely negligible compared to their single−agent counterpart. The differential responses between the cell lines correlated with driver gene mutation profiles. These findings suggest that personalised medicine approaches targeting PI3K and CDK pathways in combination may yield some benefit for mcSCC, and that more complex 3D models should be considered for drug responsiveness studies in this disease. Full article

Understanding of immune-related adverse events (irAEs) has evolved rapidly, and management guidelines are continually updated. We explored temporal changes in checkpoint inhibitor-induced irAE management at a tertiary cancer care center to identify areas for improvement. We conducted a single-center retrospective study of patients who developed a gastrointestinal, pulmonary, renal, or cardiac irAE between July and 1 October in 2019 or 2021. We collected patient demographic and clinical information up to 1 year after toxicity. Endoscopic evaluation and specialty follow-up after discharge for patients with gastrointestinal irAEs declined between the 2019 and 2021 periods. Symptom duration and steroid taper attempts also declined. For pulmonary irAEs, rates of specialty consultation, hospital admission and readmission, and mortality improved in 2021 compared with 2019. Follow-up rates after hospital discharge were consistently low (<50%) in both periods. For cardiac irAEs, consultation with a cardiologist was frequent and prompt in both periods. Outpatient treatment and earlier specialty consultation improved outcomes with gastrointestinal irAEs. Our study exploring irAE practice changes over time identified areas to improve management; specifically, timely specialty consultation was associated with better outcomes for gastrointestinal irAEs. These findings can help improve the quality of management algorithms at our institution and may inform policies in other institutions. Full article

Effective treatment options for peritoneal surface malignancies (PSMs) are scarce. Oncolytic virotherapy with recombinant vaccinia viruses might constitute a novel treatment option for PSM. We aimed to identify the most effective oncolytic vaccinia virus strain in two murine mesothelioma cell lines and the oncolytic potential in a murine model of peritoneal mesothelioma. Cell lines AB12 and AC29 were infected in vitro with vaccinia virus strains Lister (GLV-1h254), Western Reserve (GLV-0b347), and Copenhagen (GLV-4h463). The virus strain GLV-0b347 was shown most effective in vitro and was further investigated by intraperitoneal (i.p.) application to AB12 and AC29 mesothelioma-bearing mice. Feasibility, safety, and effectiveness of virotherapy were assessed by evaluating the peritoneal cancer index (PCI), virus detection in tumor tissues and ascites, virus growth curves, and comparison of overall survival. After i.p. injection of GLV-0b347, virus was detected in both tumor cells and ascites. In comparison to mock-treated mice, overall survival was significantly prolonged, ascites was less frequent and PCI values declined. However, effective treatment was only observed in animals with limited tumor burden at the time point of virus application. Nonetheless, intraperitoneal virotherapy with GLV-0b347 might constitute a novel therapeutic option for the treatment of peritoneal mesothelioma. Additional treatment modifications and combinational regimes will be investigated to further enhance treatment efficacy. Full article

Transfusions of packed red blood cells (PRBCs), given due to an oncological disease and its acute complications, are an indispensable part of anticancer therapy. However, they can lead to post-transfusion iron overload. The study aim was to evaluate the role of ferritin as a nonspecific marker of leukemic growth and marker of transfusion-related iron overload. We performed a longitudinal study of PRBC transfusions and changes in ferritin concentrations during the oncological treatment of 135 patients with childhood acute lymphoblastic and acute myeloblastic leukemia (ALL and AML, median age 5.62 years). At the diagnosis, 41% of patients had a ferritin level over 500 ng/mL, and 14% of patients had a ferritin level over 1000 ng/mL. At the cessation of the treatment, 80% of the children had serum ferritin (SF) over 500 ng/mL, and 31% had SF over 1000 ng/mL. There was no significant difference between SF at the beginning of the treatment between ALL and AML patients, but children with AML finished treatment with statistically higher SF. AML patients had also statistically higher number of transfusions. We found statistically significant positive correlations between ferritin and age, and weight and units of transfused blood. Serum ferritin at the moment of diagnosis can be a useful marker of leukemic growth, but high levels of SF are connected with iron overload in both AML and ALL. Full article

Post-hepatectomy liver failure (PHLF) represents a major cause of morbidity and mortality after liver resection. The factors related to PHLF are represented not only by the volume and function of the future liver remnant but also by the severity of portal hypertension. The aim of this study was to assess whether the preservation of the round ligament (RL) may mitigate portal hypertension, thus decreasing the risk of PHLF and ascites in cirrhotic patients while undergoing minimally invasive liver surgery (MILS). All the cirrhotic patients who underwent MILS for HCC from 2016 to 2021 in two international tertiary referral centers were retrospectively analyzed, comparing cases with the RL preserved vs. those with the RL divided. Only patients with cirrhosis ≥ Child A6, portal hypertension, and ICG-R15 > 10% were included. Main postoperative outcomes were compared, and the risk factors for postoperative ascites (severe PHLF, grade B/C) were investigated through a logistic regression. After the application of the selection criteria, a total of 130 MILS patients were identified, with 86 patients with the RL preserved and 44 with the RL divided. The RL-preserved group showed lower incidences of severe PHLF (7.0% vs. 20.5%, p = 0.023) and ascites (5.8% vs. 18.2%, p = 0.026) in comparison with the RL-divided group. After uni/multivariate analysis, the risk factors related to postoperative ascites were RL division and platelets < 92 × 10³/µL, calculated with ROC analysis. The preservation of the round ligament during MILS may mitigate portal hypertension, preventing PHLF and ascites in cirrhotic patients with borderline liver function. Full article

Background: Variations in treatment choices have been reported in colorectal cancer (CRC). In the context of national recommendations, we aimed to elucidate predictors and between-hospital variations in refraining from curatively intended surgery and adjuvant chemotherapy in potentially curable colorectal cancer. Methods: A total of 34,116 patients diagnosed with CRC from 2009 to 2018 were included for analyses on non-curative treatment in this register-based study. Subsequently 8006 patients were included in analyses on adjuvant treatment. Possible predictors included patient-, disease-, socioeconomic- and perioperative-related factors. Logistic regressions were utilized to examine the predictors of a non-curative aim of treatment and no adjuvant chemotherapy. Results: The predictors of non-curative treatment were high age, poor performance, distant metastases and being underweight. Predictors for no adjuvant treatment were high age, poor performance, kidney disease, postoperative complications and living alone. For both outcomes we found between-hospital variations to be present. Conclusions: Non-curative overall treatment and refraining from adjuvant chemotherapy were associated with well-known risk factors, but the former was also associated with being underweight and the latter was also associated with living alone. Marked between-hospital variations were found and should be examined further. Full article

Dabrafenib therapy for metastatic melanoma focuses on blocking growth-promoting signals produced by a hyperactive BRAF protein. We report the metabolic differences of four human melanoma cell lines with diverse responses to dabrafenib therapy (30 mg/kg; oral): WM3918 < WM9838BR < WM983B < DB-1. Our goal was to determine if metabolic changes produced by the altered signaling pathway due to BRAF mutations differ in the melanoma models and whether these differences correlate with response to treatment. We assessed metabolic changes in isolated cells using high-resolution proton magnetic resonance spectroscopy (¹H MRS) and supplementary biochemical assays. We also noninvasively studied mouse xenografts using proton and phosphorus (¹H/³¹P) MRS. We found consistent changes in lactate and alanine, either in isolated cells or mouse xenografts, correlating with their relative dabrafenib responsiveness. In xenografts, we also observed that a more significant response to dabrafenib correlated with higher bioenergetics (i.e., increased βNTP/Pi). Notably, our noninvasive assessment of the metabolic status of the human melanoma xenografts by ¹H/³¹P MRS demonstrated early metabolite changes preceding therapy response (i.e., tumor shrinkage). Therefore, this noninvasive methodology could be translated to assess in vivo predictive metabolic biomarkers of response in melanoma patients under dabrafenib and probably other signaling inhibition therapies. Full article

Background: Chondrosarcoma (CS) is the second most common surgically treated primary malignancy of the bone. The current study explored the effect of the margin and extraosseous tumor component in CS in the femur on local recurrence (LR), LR-free survival (LRFS), and disease-specific survival (DSS). Methods: Among 202 patients, 115 were in the proximal extremity of the femur, 4 in the corpus of the femur, and 83 in the distal extremity of femur; 105 patients had an extraosseous tumor component. Results: In the Kaplan–Meier analysis, factors significant for decreased LRFS were the extraosseous tumor component (p < 0.001), extraosseous tumor component arising from the superior aspect (p < 0.001), histological grade (p = 0.031), and narrow surgical margin < 3 mm (p < 0.001). Factors significantly affecting DSS were the histological grade (p < 0.001), extraosseous component (p < 0.001), LR (p < 0.001), metastases (p < 0.001), and surgical margin (p < 0.001). Conclusions: In CS of the femur, the presence of an extraosseous tumor component has a predictive role in LRFS, and extraosseous tumor component arising from the superior aspect was significant for decreased LRFS. Wide margins were more commonly achieved when the tumor had only an intraosseous component, and the rate of LR was significantly higher in cases with an extraosseous tumor component. When the extraosseous component arose from the superior aspect of the femur, LR occurred more frequently despite achieving adequate margins. Full article

Radiotherapy (RT) has a fundamental role in the treatment of gynecologic malignancies, including cervical and uterine cancers. Hypofractionated RT has gained popularity in many cancer sites, boosted by technological advances in treatment delivery and image verification. Hypofractionated RT uptake was intensified during the COVID-19 pandemic and has the potential to improve universal access to radiotherapy worldwide, especially in low-resource settings. This review summarizes the rationale, the current challenges and investigation efforts, together with the recent developments associated with hypofractionated RT in gynecologic malignancies. A comprehensive search was undertaken using multiple databases and ongoing trial registries. In the definitive radiotherapy setting for cervical cancers, there are several ongoing clinical trials from Canada, Mexico, Iran, the Philippines and Thailand investigating the role of a moderate hypofractionated external beam RT regimen in the low-risk locally advanced population. Likewise, there are ongoing ultra and moderate hypofractionated RT trials in the uterine cancer setting. One Canadian prospective trial of stereotactic hypofractionated adjuvant RT for uterine cancer patients suggested a good tolerance to this treatment strategy in the acute setting, with a follow-up trial currently randomizing patients between conventional fractionation and the hypofractionated dose regimen delivered in the former trial. Although not yet ready for prime-time use, hypofractionated RT could be a potential solution to several challenges that limit access to and the utilization of radiotherapy for gynecologic cancer patients worldwide. Full article

Glioblastoma is the most frequent and malignant primary neoplasm of the central nervous system. In a recent breakthrough study on a prospective Discovery cohort, I proposed the first all-inclusive molecular classification of glioblastoma into seven subgroups, G1-G7, based on MAPK pathway activation. New data from a WHO-grade-4 diffuse glioma prospective Validation cohort offers, in this study, an integrated demographic–molecular analysis of a 213-patient Combined cohort. Despite cohort differences in the median age and molecular subgroup distribution, all the prospectively-acquired cases from the Validation cohort mapped into one of the G1-G7 subgroups defined in the Discovery cohort. A younger age of onset, higher tumor mutation burden and expanded G1/EGFR-mutant and G3/NF1 glioblastoma subgroups characterized the glioblastomas from African American/Black relative to Caucasian/White patients. The three largest molecular subgroups were G1/EGFR, G3/NF1 and G7/Other. The fourth largest subgroup, G6/Multi-RTK, was detailed by describing a novel gene fusion ST7–MET, rare PTPRZ1–MET, LMNA–NTRK1 and GOPC–ROS1 fusions and their overexpression mechanisms in glioblastoma. The correlations between the MAPK pathway G1-G7 subgroups and the PI3-kinase/PTEN, TERT, cell cycle G1 phase and p53 pathways defined characteristic subgroup pathway profiles amenable to personalized targeted therapy. This analysis validated the first all-inclusive molecular classification of glioblastoma, showed significant demographic and molecular differences between subgroups, and provided the first ethnic molecular comparison of glioblastoma. Full article

Options for treatment of incurable cancer remain scarce and are largely focused on limited therapeutic mechanisms. A new approach specific to advanced cancers is needed to identify new and effective treatments. Morbidity in advanced cancer is driven by functional decline and a number of systemic conditions, including cachexia and fatigue. This review will focus on these clinical concepts, describe our current understanding of their underlying biology, and then propose how future therapeutic strategies, including pharmaceuticals, exercise, and rehabilitation, could target these mechanisms as an alternative route to addressing incurable cancer. Full article

(1) Background: Pancreatic adenocarcinoma (PAC) is one of the most lethal types of cancer. Most cases of PAC occur in the head of the pancreas. Given the proximity of the pancreatic head to the bile duct, most patients present clinically during early stages of the disease, while distally located PAC could have delayed clinical presentation. (2) Aims: To assess predictors of non-head PAC. (3) Methods: A retrospective multicenter study was conducted, including all patients who had endoscopic ultrasound (EUS) for pancreatic masses and who had histologic confirmation of PAC. (4) Results: Of the 151 patients included, 92 (60.9%) had pancreatic head cancer, and 59 (39.1%) had distal pancreatic cancer. PAC at body was the most common location in the distal PAC group (31 patients (52.5%)). Logistic regression analysis demonstrated a significant association of obesity with distal migration of PAC (OR 4.44, 95% CI 1.15–17.19, p = 0.03), while none of the other assessed parameters showed a significant association. Notably, abdominal pain was more significantly associated with distal PAC vs. head location (OR 2.85, 95% CI 1.32–6.16, p = 0.008). (5) Conclusions: Obesity shows a significant association as a clinical predictor of distal PAC. Further studies are needed to better explore this association. Full article