The Critical Role of the Early Evaluation of Iron and Vitamin B12 Deficiency in Pregnancy.

Background and objective Anemia is a common hematological disorder during pregnancy, with iron deficiency (ID) being the most prevalent cause globally. It severely affects maternal and fetal health. This study aimed to investigate the prevalence of anemia and its association with iron and vitamin B12 deficiency during pregnancy. Materials and methods The study sample consisted of pregnant women attending the 3rd Clinic of Obstetrics and Gynecology, University General Hospital "Attikon", Athens, Greece, with a total of 145 women eventually analyzed. Blood samples were collected from pregnant women during the first, second, and third trimesters; hematological indices, including hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red blood cell distribution width (RDW), ferritin, and vitamin B12, were recorded. Iron deficiency anemia was defined as HGB <11.0 g/dl in the first trimester and <10.5 g/dl in the second and third trimesters. Results Iron deficiency anemia is elevated in the course of pregnancy. A significant proportion of pregnant women had vitamin B12 deficiency during pregnancy, with the prevalence increasing from the first to the third trimester. The study also found that iron supplementation improved hematological indices; especially, pregnant women receiving divalent iron had significantly higher levels of HCT, HGB, and ferritin compared to those receiving trivalent iron. Conclusions Screening for iron deficiency anemia should be performed in all pregnant women, and appropriate oral iron therapy should be given as first-line treatment. Early recognition and management of low maternal iron levels are crucial and lead to improved maternal, fetal, and neonatal outcomes. Furthermore, unified international thresholds for ID are required for accurate assessments and appropriate iron supplementing. This study also recommends the screening of vitamin B12 levels as part of the systematic follow-up of pregnant women to identify potential deficiencies and provide appropriate supplementation. Further in-depth studies, particularly related to vitamin B12, are required to provide definitive conclusions and guidance.

Proton-Based Radiation Therapy for Skull Base Chondrosarcomas in Children and Adolescents: 40-year experience from a single institution.

BACKGROUND: The literature on skull base chondrosarcoma (CHS) is scarce. We report outcomes for pediatric and young patients ≤ 22 years with base of skull (BOS) CHSs treated with proton-based radiotherapy (PBRT). METHODS: We retrospectively reviewed all patients treated with PBRT between 1981 and 2023. Primary endpoints were overall survival (OS), chondrosarcoma-specific survival (CSS), progression-free survival (PFS), local control (LC), and distal control (DC). RESULTS: Eighty-four patients were identified. Median age at diagnosis was 19 years (range, 6 - 22). Most patients (n=79, 94%) had conventional CHS while 5 (6%) had mesenchymal CHS. Nine patients (11%) underwent gross total resection (GTR), 64 (76%) subtotal resection (STR) and 11 patients (13%) underwent biopsy. Twenty-four (29%) patients progressed prior to radiotherapy (RT). The median prescription dose was 70 Gy (RBE) (range, 50 - 79.7). At a median follow-up of 18.0 years [interquartile range (IQR),), 9.2 -26.2] from diagnosis, 11 patients recurred (7 local, 4 distant). Six patients died of disease. Five patients died of other causes. Ten-year OS, CSS and PFS rates for all patients were 93.3%, 94.7% and 88%, respectively. Twenty-year OS, CSS and PFS rates for conventional CHS (n=79) were 93.1%, 97.1% and 89.2%, respectively. Mesenchymal histology was significantly associated with worse OS and PFS. Pre-RT tumor progression portended worse OS and CSS. Eight patients (9.9 %) experienced a late toxicity grade 3 or greater. CONCLUSIONS: This is the largest cohort of pediatric BOS CHSs in literature to date. High-dose PBRT following surgical resection achieves excellent disease control with minimal toxicity.

Synthesis and Biological Evaluation of Novel Cationic Rhenium and Technetium-99m Complexes Bearing Quinazoline Derivative for Epidermal Growth Factor Receptor Targeting.

Background/Objectives: Epidermal growth factor receptor (EGFR) plays a vital role in cell proliferation and survival, with its overexpression linked to various malignancies, including non-small cell lung cancer (NSCLC). Although EGFR tyrosine kinase inhibitors (TKIs) are a key therapeutic strategy, acquired resistance and relapse remain challenges. This study aimed to synthesize and evaluate novel rhenium-based complexes incorporating EGFR TKIs to enhance anticancer efficacy, particularly in radiosensitization. Methods: We synthesized a rhenium tricarbonyl complex (Complex 2) and its 99mTc analog (Complex 2') by incorporating triphenylphosphine instead of bromine as the monodentate ligand and PF6- as the counter-ion, resulting in a positively charged compound that forms cationic structures. Cytotoxicity and EGFR inhibition were evaluated in A431 cells overexpressing EGFR using MTT assays, Western blotting, and flow cytometry. Radiosensitization was tested through MTT and clonogenic assays. The 99mTc complex's radiochemical yield, stability, and lipophilicity were also assessed. Results: Complex 2 exhibited significant cytotoxicity with an IC50 of 2.6 µM and EGFR phosphorylation inhibition with an IC50 of 130.6 nM. Both complex 1 and 2 induced G0/G1 cell cycle arrest, with Complex 2 causing apoptosis. Radiosensitization was observed at doses above 2 Gy. Complex 2' demonstrated high stability and favorable lipophilicity (LogD7.4 3.2), showing 12% cellular uptake after 30 min. Conclusions: Complexes 2 and 2' show promise as dual-function anticancer agents, offering EGFR inhibition, apoptosis induction, and radiosensitization. Their potential as radiopharmaceuticals warrants further in-depth investigation in preclinical models.

Robotic Stereotactic Body Radiation Therapy for Oligometastatic Liver Metastases: A Systematic Review of the Literature and Evidence Quality Assessment.

INTRODUCTION: The role of stereotactic body radiation therapy (SBRT) as a locally effective therapeutic approach for liver oligometastases from tumors of various origin is well established. We investigated the role of robotic SBRT (rSBRT) treatment on oligometastatic patients with liver lesions. MATERIAL AND METHODS: This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. The PubMed and Scopus databases were accessed by two independent investigators concerning robotic rSBRT for liver metastases, up to 3 October 2023. RESULTS: In total, 15 studies, including 646 patients with 847 lesions that underwent rSBRT, were included in our systematic review. Complete response (CR) after rSBRT was achieved in 40.5% (95% CI, 36.66-44.46%), partial response (PR) in 19.01% (95% CI, 16.07-22.33%), whereas stable disease (SD) was recorded in 14.38% (95% CI, 11.8-17.41%) and progressive disease (PD) in 13.22% (95% CI, 10.74-16.17%) of patients. Progression-free survival (PFS) rates at 12 and 24 months were estimated at 61.49% (95% CI, 57.01-65.78%) and 32.55% (95% CI, 28.47-36.92%), respectively, while the overall survival (OS) rates at 12 and 24 months were estimated at 58.59% (95% CI, 53.67-63.33%) and 44.19% (95% CI, 39.38-49.12%), respectively. Grade 1 toxicity was reported in 13.81% (95% CI, 11.01-17.18%), Grade 2 toxicity in 5.57% (95% CI, 3.82-8.01%), and Grade 3 toxicity in 2.27% (955 CI, 1.22-4.07%) of included patients. CONCLUSIONS: rSBRT represents a promising method achieving local control with minimal toxicity in a significant proportion of patients. Further studies are needed to evaluate the role of rSBRT in the management of metastatic liver lesions.

Pseudomyxoma Peritonei: A Challenging Clinical Diagnosis. Case Report and Review of the Literature.

Background: Pseudomyxoma peritonei (PMP) is a clinical entity of subtle onset abdominal pain, ascites, and distention associated with characteristic imaging. In most cases, laparoscopic exploration will give the definitive diagnosis and histopathologic verification. However, usually there are difficulties in the diagnosis of this disease. Case Report: Herein, we present a case of a 51-year-old female who developed ascites over 5 months. An investigational laparotomy established the diagnosis of PMP, after the discovery of a mucinous, grey-brown tumor that was CK20 positive and CK7 negative. Subsequently, chemotherapy with oxaliplatin combined with 5-FU (FOLFOX4 regimen), was initiated and the patient survived for 30 months. We also present a comprehensive review of the English literature concerning the different symptoms and radiological findings of this rare entity. According to the literature review, 35 cases of PMP with different clinical and radiological findings have been described. In the majority of the cases, ultrasound, computed tomography or magnetic resonance imaging was orientating towards a proper diagnosis before a diagnostic laparotomy. Conclusion: The combination of a clinical picture with the characteristic imaging findings enables a prompt diagnosis of PMP, making prognosis more favorable.

Radiation Dose to Critical Cardiac Structures from Three-Dimensional Conformal Radiation Therapy (3D-CRT), Intensity-Modulated Radiation Therapy (IMRT) and Volumetric Modulated Arc Therapy (VMAT) Techniques for Left-Sided Breast Cancer.

A comparison of the radiation exposure to the left anterior descending artery (LAD) and left ventricle (LV) was performed for twenty-three left breast cancer patients. For each participant, two tangential fields 3D-CRT, two- and seven-field IMRT and two and four partial arcs VMAT plans were created. Dose constraints for CTV, ipsilateral lung and heart were followed. The V40Gy, V30Gy, Dav of LAD and V23Gy, V5Gy, Dav of LV were calculated and extracted from the plans. Parametric and non-parametric tests were applied to compare the parameters derived from the five treatment techniques. All generated plans fulfilled the dose constraints. The Dav ranges of the LAD and LV from all examined techniques were 11.77-14.73 Gy and 5.37-6.40 Gy, respectively. The V40Gy and V30Gy ranges of the LAD were 2.90-12.91% and 10.80-18.51%, respectively. The V23Gy and V5Gy of the LV were 4.29-7.43% and 18.24-30.05%, respectively. The VMAT plans and seven-field IMRT significantly reduced the V40Gy, V30Gy of LAD and V23Gy of LV compared with the two-field treatments (p < 0.05). However, 3D-CRT plans provided statistically lower values for V5Gy of LV over the other techniques (p < 0.05). The presented results provide a detailed dataset of the radiation burden of two critical cardiac structures from five radiotherapy techniques.

Association of Mediterranean Diet Adherence with Disease Progression Characteristics, Lifestyle Factors and Overall Survival in Gastric Cancer Patients.

BACKGROUND: The Mediterranean diet (MD) exerts a protective effect against cancer development and progression; however, the evaluation of its impact on gastric cancer still remains quite scarce. The present study aims to evaluate the association of MD adherence during the lifespan with disease progression characteristics, lifestyle factors and overall survival in gastric carcinoma patients. METHODS: This is an observational, cross-sectional study conducted on 186 gastric cancer patients followed up for a median time interval of 57 months or until death due to cancer disease. Tumor histopathological characteristics were retrieved from patients' medical records, while validated questionnaires assessing, immediately after the time of diagnosis, health-related quality of life, physical activity levels, sleep quality, depression, anxiety and MD adherence during the lifespan were used. RESULTS: Higher MD adherence during the lifespan was significantly associated with younger patients (p = 0.0106), regular smoking (p < 0.0001), abnormal BMI status (p < 0.0001), intestinal-type gastric carcinoma (p = 0.0111), high tumor histopathological grade (p < 0.0001) and earlier disease stage (p < 0.0001). Moreover, patients with elevated MD adherence during their lifespan showed significantly better health-related quality of life (p < 0.0001), higher physical activity levels (p < 0.0001), more adequate sleep quality (p < 0.0001) and lower prevalence of depression (p = 0.0003) and anxiety (p = 0.0006) compared to those with reduced MD adherence. In multiple regression analysis, elevated MD compliance during the lifespan was independently correlated with longer overall patient survival after adjustment for several confounders (Cox regression analysis, p = 0.0001). CONCLUSIONS: Higher MD adherence during the lifespan was associated with less advanced tumor histopathology characteristics and favorable mental and physical lifestyle factors. Moreover, higher MD adherence during the lifespan was also independently correlated with longer overall survival in gastric carcinoma patients. Thus, adopting a healthy dietary pattern like the MD during the lifespan may act as a preventive agent in combination with a healthy lifestyle against gastric cancer development and progression.

Retroperitoneal Soft Tissue Sarcoma: Emerging Therapeutic Strategies.

Retroperitoneal soft tissue sarcoma (RPS) is a rare and heterogenous disease for which surgery is the cornerstone of treatment. However, the local recurrence rate is much higher than in soft tissue sarcoma of the extremities since wide resection is usually unfeasible in RPS due to its large size, indistinct tumour borders, anatomical constraints and the thinness of the overlying peritoneum. Local recurrence is the leading cause of death for low-grade RPS, whereas high-grade tumours are prone to distant metastases. In recent decades, the role of emerging therapeutic strategies, such as more extended surgery and (neo)adjuvant treatments to improve oncological outcome in primary localised RPS, has been extensively investigated. In this review, the recent data on the evolving multidisciplinary management of primary localised RPS are comprehensively discussed. The heterogeneity of RPS, with their different histological subtypes and biological behaviour, renders a standard therapeutic 'one-size-fits-all' approach inappropriate, and treatment should be modified according to histological type and malignancy grade. There is sufficient evidence that frontline extended surgery with compartmental resection including all ipsilateral retroperitoneal fat and liberal en bloc resection of adjacent organs and structures, even if they are not macroscopically involved, increases local tumour control in low-grade sarcoma and liposarcoma, but not in leiomyosarcoma for which complete macroscopic resection seems sufficient. Additionally, preoperative radiotherapy is not indicated for all RPSs, but seems to be beneficial in well-differentiated liposarcoma and grade I/II dedifferentiated liposarcoma, and probably in solitary fibrous tumour. Whether neoadjuvant chemotherapy is of benefit in high-grade RPS remains unclear from retrospective data and is subject of the ongoing randomised STRASS 2 trial, from which the results are eagerly awaited. Personalised, histology-tailored multimodality treatment is promising and will likely further evolve as our understanding of the molecular and genetic characteristics within RPS improves.

The Clinical Significance of MicroRNAs in Colorectal Cancer Signaling Pathways: A Review.

Colorectal carcinoma (colon and rectum) is currently considered among the most prevalent malignancies of Western societies. The pathogenesis and etiological mechanisms underlying colorectal cancer (CRC) development remain complex and heterogeneous. The homeostasis and function of normal human intestinal cells is highly regulated by microRNAs. Therefore, it is not surprising that mutations and inactivation of these molecules appear to be linked with progression of colorectal tumors. Recent studies have reported significant alterations of microRNA expression in adenomas and CRCs compared with adjacent normal tissues. This observed deviation has been proposed to correlate with the progression and survival of disease as well as with choice of optimal treatment and drug resistance. MicroRNAs can adopt either oncogenic or tumor-suppressive roles during regulation of pathways that drive carcinogenesis. Typically, oncogenic microRNAs termed oncomirs, target and silence endogenous tumor-suppressor genes. On the other hand, tumor-suppressive microRNAs are critical in downregulating genes associated with cell growth and malignant capabilities. By extensively evaluating robust studies, we have emphasized and distinguished a discrete set of microRNAs that can modulate tumor progression by silencing specific driver genes crucial in signaling pathways including Wnt/b-catenin, epidermal growth factor receptor, P53, mismatch repair DNA repair, and transforming-growth factor beta.

May Nutritional Status Positively Affect Disease Progression and Prognosis in Patients with Esophageal and Pharyngeal Cancers? A Scoping Review of the Current Clinical Studies.

BACKGROUND: Malnutrition in esophageal and pharyngeal cancer patients constitutes a common and serious concern, which significantly reduces patients' prognoses. Cancers of the esophagus and the pharynx can considerably impair feeding in patients, resulting in severe undernutrition. This is a scoping review that intends to critically analyze the most well-designed clinical studies investigating the potential beneficial impact of diverse nutritional assessment tools on the prognosis of patients with esophageal and pharyngeal cancers. METHODS: The most accurate and remarkable scientific databases were comprehensively explored utilizing relative keywords to detect clinical studies that investigate whether nutritional status may affect disease prognosis. RESULTS: Several assessment tools have evaluated and highlighted the potential beneficial impact of nutritional status on disease progression and patients' prognosis in both esophageal and pharyngeal cancers. Regarding esophageal cancer, CONUT, PNI, PG-SGA, and NRS-2002 are more commonly used, while albumin is also frequently evaluated. Regarding pharyngeal cancers, fewer studies are currently available. PNI has been evaluated, and its significance as a factor for shorter survival' times has been highlighted. The Comprehensive Nutritional Index has also been evaluated with positive results, as well as NRS 2002, GPS, and body-weight status. However, there is currently a lack of studies with an adequate number of women with cancer. An international literature gap was identified concerning follow-up studies with adequate methodology. CONCLUSIONS: Nutritional status may significantly affect disease progression and patients' survival, highlighting the significance of a great nutritional status in individuals with esophageal and pharyngeal cancers. Further large-scale and well-designed prospective surveys should be performed to verify the potential beneficial effects of adequate nourishment in people suffering from cancer of the esophagus and pharynx.

NTCP Calculations of Five Different Irradiation Techniques for the Treatment of Thymoma.

This study provided normal tissue complication probability (NTCP) calculations from photon radiotherapy techniques in eleven patients with thymoma. Five plans were created for each participant using three-dimensional conformal radiotherapy (3D-CRT), five-field intensity modulated radiotherapy (5F-IMRT), seven-field IMRT (7F-IMRT), and volumetric modulated arc therapy with full arcs (FA-VMAT) and partial arcs (PA-VMAT). The target coverage, homogeneity index and conformation number for the planning target volume (PTV) and dosimetric parameters for the organs-at-risk (OARs) were taken from the fifty-five generated plans. The patient-specific NTCP of the lungs, heart and esophagus was calculated with an in-house software tool using differential dose-volume histograms and the equivalent uniform dose model. The PTV dose metrics from 3D-CRT were inferior to those from IMRT and VMAT plans. The dose constraints for the OARs were met in all treatment plans. The NTCP range of the lungs, heart and esophagus was 0.34-0.49%, 0.03-0.06% and 0.08-0.10%, respectively. The NTCPs of the heart for the incidence of peridarditis from IMRT and VMAT were significantly smaller than those from conformal treatment (p < 0.05). The 7F-IMRT was significantly superior to FA-VMAT in reducing the NTCP of the lungs and the risk of pneumonitis (p = 0.001). Similar superiority of 5F-IMRT over PA-VMAT for lung protection was found (p = 0.009). The presented results may be employed in the selection of the appropriate irradiation technique for restricting the complications in the adjacent OARs.

Intermittent Fasting against Cancer Development and Progression: Highlighting Potential Anticancer Molecular Mechanisms.

BACKGROUND: Intermittent fasting (IF) diets have been popular since the last few decades because of their provable clinical efficiency on weight control of the subjects. These diet types are generally safe, resulting in health promoting effects against several human diseases like cardiovascular diseases, diabetes mellitus, neurogenerative disorders and cancer. OBJECTIVE: To review whether IF can act against cancer development and progression, highlighting potential anticancer molecular mechanisms in clinical studies. METHODS: Applied summarization of the available clinical studies investigating the effectiveness of IF against cancer development and progression and cancer-induced indicators. Scientific databases, e.g., PubMed, and Scopus, were comprehensively searched using relative words to identify in vivo and in vitro data, as well as clinical studies. RESULTS: IF seems to exert health-promoting effects in cancer patients through induction of autophagy, which enhances the in vivo suppression of tumor development, by chemotherapy. IF provokes tumors to chemotherapy and defends the normal cells from its adverse side effects, increasing the immune response. In addition, it enhances the cytotoxic CD8(+) tumor-infiltrating lymphocytes and the bone marrow lymphoid progenitor cells, delaying the cancer progression. IF reduces oxidative stress via repression of translation and induces cellular apoptosis. Fasting exerts anti-aging properties modulating the secretion of IGF-1, IGFBP-1, glucose, and insulin while, at the same time, it integrates cell adaptive responses and activates cell signaling pathways which stimulates antioxidant defenses, DNA repairment, control of protein quality, mitochondrial synthesis while decreasing inflammation. CONCLUSION: IF appears to exert health promoting effects against cancer development and progression, suppressing several kinds of cancer. There are well-recognized and not well-recognized molecular processes accentuating its anticancer outcomes; however, well-designed clinical trials and further molecular studies are strongly recommended.

Current Cardioprotective Strategies for the Prevention of Radiation-Induced Cardiotoxicity in Left-Sided Breast Cancer Patients.

BACKGROUND: Breast cancer (BC) is the most common malignancy in females, accounting for the majority of cancer-related deaths worldwide. There is well-established understanding about the effective role of radiotherapy (RT) in BC therapeutic strategies, offering a better local-regional control, prolonged survival, and improved quality of life for patients. However, it has been proven that conventional RT modalities, especially in left-sided BC cases, are unable to avoid the administration of high RT doses to the heart, thus resulting in cardiotoxicity and promoting long-term cardiovascular diseases (CVD). Recent radiotherapeutic techniques, characterized by dosimetric dose restrictions, target volume revision/modifications, an increased awareness of risk factors, and consistent follow-ups, have created an advantageous context for a significant decrease inpost-RT CVD incidence. AIM: This review presents the fundamental role of current cardioprotective strategies in the prevention of cardiotoxic effects in left-BCRT. MATERIAL AND METHODS: A literature search was conducted up to January 2023 using the Cochrane Central Register of Controlled Trials and PubMed Central databases. Our review refers to new radiotherapeutic techniques carried out on patients after BC surgery. Specifically, a dose evaluation of the heart and left anterior descending coronary artery (LADCA) was pointed out for all the included studies, depending on the implemented RT modality, bed positioning, and internal mammary lymph nodes radiation. RESULTS: Several studies reporting improved heart sparing with new RT techniques in BC patients were searched. In addition to the RT modality, which definitely determines the feasibility of achieving lower doses for the organs at risk (OARs), better target coverage, dose conformity and homogeneity, and the patient's position, characteristics, and anatomy may also affect the evaluated RT dose to the whole heart and its substructures. CONCLUSIONS: Modern BC RT techniques seem to enable the administration of lower doses to the OARs without compromising on the target coverage. The analysis of several anatomical parameters and the assessment of cardiac biomarkers potentiate the protective effect of these new irradiation modalities, providing a holistic approach to the radiation-associated risks of cardiac disease for BC patients. Despite technological advances, an inevitable cardiac radiation risk still exists, while adverse cardiac events may be observed even many years after RT. Studies with longer follow-ups are required in order to determine the effectiveness of modern breast RT techniques.

Metformin: A Promising Radiosensitizer in Neoadjuvant Rectal Cancer Treatment.

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) decreases the risk of local recurrence after surgery in patients with locally advanced rectal cancer (LARC) and metformin is constantly gaining scientific interest due to its potentially radiosensitizing effect. OBJECTIVE: This review article aims to better clarify the role of metformin as a radiosensitizer in patients with LARC undergoing neoadjuvant concurrent chemoradiotherapy. METHODS: We used the PubMed database to retrieve journal articles and the inclusion criteria were all human studies that illustrated the effective role of metformin in the neoadjuvant setting of locally advanced rectal cancer. RESULTS: Our search resulted in 17 citations, of which 10 eventually fulfilled the inclusion criteria of our study. Promising results (improved tumor and nodal regression as well as higher pathologic complete response rate) have been occasionally documented with metformin use in some of the included studies. However, regarding survival and all-cause mortality, no significant difference has been found. CONCLUSION: Metformin might constitute a highly promising radiosensitizer in neoadjuvant LARC treatment attracting much scientific interest. Due to the lack of studies with high evidence, further advanced research is required to enhance the existing knowledge about its potential value in this field.

Role of telomere length in human carcinogenesis (Review).

Cancer is considered the most important clinical, social and economic issue regarding cause­specific disability­adjusted life years among all human pathologies. Exogenous, endogenous and individual factors, including genetic predisposition, participate in cancer triggering. Telomeres are specific DNA structures positioned at the end of chromosomes and consist of repetitive nucleotide sequences, which, together with shelterin proteins, facilitate the maintenance of chromosome stability, while protecting them from genomic erosion. Even though the connection between telomere status and carcinogenesis has been identified, the absence of a universal or even a cancer­specific trend renders consent even more complex. It is indicative that both short and long telomere lengths have been associated with a high risk of cancer incidence. When evaluating risk associations between cancer and telomere length, a disparity appears to emerge. Even though shorter telomeres have been adopted as a marker of poorer health status and an older biological age, longer telomeres due to increased cell growth potential are associated with the acquirement of cancer­initiating somatic mutations. Therefore, the present review aimed to comprehensively present the multifaceted pattern of telomere length and cancer incidence association.

Exosomal MicroRNA-223, MicroRNA-146, and MicroRNA-21 Profiles and Biochemical Changes in Laryngeal Cancer.

Laryngeal squamous cell carcinoma (LSCC) is one of the most aggressive cancers, and its early diagnosis is urgent. Exosomes are believed to have diagnostic significance in cancer. However, the role of serum exosomal microRNAs, miR-223, miR-146, and miR-21, and phosphatase and tensin homologue (PTEN) and hemoglobin subunit delta (HBD) mRNAs in LSCC is unclear. Exosomes were isolated from the blood serum of 10 LSCC patients and 10 healthy controls to perform scanning electron microscopy and liquid chromatography quadrupole time-of-flight mass spectrometry analyses to characterize them and to undergo reverse transcription polymerase chain reaction to identify miR-223, miR-146, miR-21, and PTEN and HBD mRNA expression phenotypes. Biochemical parameters, including serum C-reactive protein (CRP) and vitamin B12, were also obtained. Serum exosomes of 10-140 nm were isolated from LSCC and controls. Serum exosomal miR-223, miR-146, and PTEN were found to be significantly decreased (p < 0.05), in contrast to serum exosomal miRNA-21 (p < 0.01), and serum vitamin B12 and CRP (p < 0.05) were found to be significantly increased, in LSCC vs controls. Our novel data show that the combination of reduced serum exosomal miR-223, miR-146, and miR-21 profiles and biochemical alterations in CRP and vitamin B12 levels may be useful indicators of LSCC that could be validated by large studies. Our findings also suggest a possible negative regulatory effect of miR-21 on PTEN in LSCC, encouraging a more extensive investigation of its role.

Surgery and proton radiation therapy for pediatric base of skull chordomas: Long-term clinical outcomes for 204 patients.

BACKGROUND: Data on clinical outcomes for base of skull (BOS) chordomas in the pediatric population is limited. We report patient outcomes after surgery and proton radiotherapy (PRT). METHODS: Pediatric patients with BOS chordomas were treated with PRT or combined proton/photon approach (proton-based; for most, 80% proton/20% photon) at the Massachusetts General Hospital from 1981 to 2021. Endpoints of interest were overall survival (OS), disease-specific survival, progression-free survival (PFS), freedom from local recurrence (LC), and freedom from distant failure (DC). RESULTS: Of 204 patients, median age at diagnosis was 11.1 years (range, 1-21). Chordoma location included 59% upper and/or middle clivus, 36% lower clivus, 4% craniocervical junction, and 1% nasal cavity. Fifteen (7%) received pre-RT chemotherapy. Forty-seven (23%) received PRT, and 157 (77%) received comboRT. Median total dose was 76.7 Gy (RBE) (range, 59.3-83.3). At a median follow-up of 10 years (interquartile range, 5-16 years), 56 recurred. Median OS and PFS were 26 and 25 years, with 5-, 10-, and 20-year OS and PFS rates of 84% and 74%, 78% and 69%, and 64% and 64%, respectively. Multivariable actuarial analyses showed poorly differentiated subtype, radiographical progression prior to RT, larger treatment volume, and lower clivus location to be prognostic factors for worse OS, PFS, and LC. RT was well tolerated at a median follow-up of 9 years (interquartile range, 4-16 years). Side effects included 166 patients (80%) with mild/moderate acute toxicities, 24 (12%) patients with late toxicities, and 4 (2%) who developed secondary radiation-related malignancies. CONCLUSION: This is the largest cohort of BOS chordomas in the literature, pediatric and/or adult. High-dose PRT following surgical resection is effective with low rates of late toxicity.

Immune checkpoint inhibitors and combinations with other agents in cholangiocarcinoma.

Cholangiocarcinoma consists of a heterogeneous group of malignancies with generally poor prognoses. Immunotherapy has emerged in the treatment landscape of many tumors, offering survival benefits, but data regarding the use of immunotherapy for cholangiocarcinoma remain vague. In this review, the authors analyze differences in the tumor microenvironment and various immune escape mechanisms and discuss available immunotherapy combinations with other agents among completed and ongoing clinical trials, such as chemotherapy, targeted agents, antiangiogenic drugs, local ablative therapies, cancer vaccines, adoptive cell therapy and PARP and TGF-ß inhibitors. Ongoing research to identify appropriate biomarkers is warranted.

Cholangiocarcinomas are a group of rare tumors. Survival time is limited, due to late diagnosis and advanced symptoms. The small number of patients makes it difficult to carry out clinical trials and find new medicines. Another issue is that there are many different subtypes of this tumor. Each one requires a different approach. Despite these setbacks, new treatment choices have appeared. Medicines that stimulate the immune system to fight cancer cells have changed the current treatment landscape for many tumor types and are very promising in cholangiocarcinomas.

Maternal Gestational Diabetes Is Associated with High Risk of Childhood Overweight and Obesity: A Cross-Sectional Study in Pre-School Children Aged 2-5 Years.

Background and Objectives: Childhood obesity is a global public health concern with long-term and serious health implications. An important factor for childhood obesity is maternal gestational diabetes mellitus (GDM), which in turn impacts maternal and offspring long-term health. This study aimed to investigate the associations between maternal GDM and childhood weight status and multiple anthropometric and sociodemographic factors and perinatal outcomes. Materials and Methods: A total of 5348 children aged 2-5 years old and their paired mothers took part in the study. Questionnaires were utilized to evaluate the sociodemographic factors and perinatal outcomes as well as smoking habits, educational level, economic status, age, and parity status. Children's anthropometric parameters were measured, and maternal medical history, preterm birth records, and anthropometric measures during pregnancy were retrieved by their medical records. Results: Overall, 16.4% of the children aged at 2-5 years were overweight, and 8.2% of them were affected by obesity, leading to a total 24.6% of children with overweight/obesity. Further, 5.5% of the enrolled mothers were diagnosed with gestational diabetes mellitus. GDM doubles the probability of childhood overweight/obesity at ages 2-5 years old independently of multiple confounding factors. Pre-pregnancy overweight and obesity, older maternal age, and smoking are risk factors for GDM, while GDM additionally increases the risk of preterm birth. Children of mothers that developed GDM were at greater risk of overweight or obesity, with the association between GDM and offspring's weight status being independent of confounding factors. Conclusions: GDM is a severe public health issue with prolonged complications for both the mother and their children. Public health approaches and programs need to promote the negative role of pre-pregnancy weight and smoking status as well as the significance of a good glycemic control throughout gestation in women of childbearing age.

Metachronous Single Pulmonary Metastasis of Prostate Cancer: Report of a Rare Case and Literature Review.

BACKGROUND: Prostate cancer recurrence after definitive local therapy usually involves the bone and regional lymph nodes. CASE REPORT: We present the case of a 72-year-old male patient with an isolated lung nodule, seven years after radical prostatectomy for prostate cancer, pT2bN0 and Gleason score 7(4+3), and prostatic-specific antigen (PSA) levels within normal limits. The nodule was considered as a primary lung cancer and the patient was subjected to lobectomy. The immunohistochemical staining showed that the tumor was PSA(+) and NKX3.1 (+), revealing that it was metastasis from prostatic cancer and that wedge resectomy was the proper procedure. Three years later the patient is disease-free, suggesting the importance of aggressive treatment of oligometastatic disease. CONCLUSION: Metastasis to the lung is present in more than 40% of men with metastatic prostate cancer; however, lung metastases without any bone or lymph node involvement are extremely rare and only a handful of cases are reported in the literature. Surgical excision of the metastatic lung site is the most common therapeutic approach associated with a good prognosis.