Search Results (56)

Background/Objectives: Myxoid liposarcoma (MLS) is a malignant soft-tissue tumor and the second-most common subtype of liposarcoma, often occurring in the lower limbs of middle-aged patients. Case Presentation: A 38-year-old male patient presented to the ultrasound outpatient clinic with a large mass in the right femoral region. It has been present for 15 years and mostly stable in size. Over the last two years, it has been slowly increasing in size, more rapidly in the previous 10 months, and has started to limit his range of motion. After multiparametric ultrasound and magnetic resonance imaging evaluation, the proposed diagnosis was myxoid liposarcoma. Following imaging workup, the patient was referred to the tertiary sarcoma center, where a biopsy was performed, and pathohistological diagnosis was low-grade myxoid liposarcoma. Contrast-enhanced computed tomography (CT) evaluation of the thorax, abdomen, and pelvis showed no signs of dissemination, and CT angiography showed no signs of vessel infiltration. Plastic surgery and vascular surgery specialists performed the extirpation of the mass with the partial resection of the adjacent sartorius muscle and the complete resection of the great saphenous vein. Subsequent pathohistological analysis of the mass and local lymph nodes showed clear surgical margins and no lymphatic or vascular invasion. The patient is currently under regular surveillance by an oncology specialist and awaiting adjuvant radiotherapy. Conclusions: A multidisciplinary approach is essential in the management of patients with MLS, as it provides a tailored, individualized assessment from diagnosis through treatment to ensure the best possible outcome. Full article

Objective: An important characteristic of Hepatocellular carcinoma (HCC) is that it features multicentric recurrences that can recur after curative treatment. Current recommended curative treatments for HCC include liver transplantation (LT), and prognostic evaluation and appropriate treatment selection are crucial in the management of HCC patients. Factors considered tend to include tumor size and number, lobar distribution, multinodularity, α-fetoprotein (AFP) level, degree of tumor differentiation, vascular invasion, and satellite nodules. However, the prognostic value of intrahepatic lymphatic vessel invasion (LVI) has rarely been reported for liver cancers. Methods: From January 2012 to December 2020, a total of 178 HCC patients who underwent liver transplantation consecutively were retrospectively enrolled. Those who underwent liver transplantation were divided into two groups based on the presence or absence of lymphatic vessel invasion. The primary aim was to compare the two groups for overall survival (OS), disease free survival (DFS), and recurrence rates, as well as to evaluate the prognostic effect of LVI after transplantation. Results: Poor tumor characteristics such as high tumor differentiation grade and MVI were significantly higher in the patient group with LI. Tumor recurrence and mortality rates were significantly higher in LI-positive recipients. Conclusions: The lymphatic invasion (LI) group displayed higher rates of recurrence and mortality. The findings emphasize the need to incorporate LI assessment into prognostic evaluations to enhance the management and outcomes of individuals with Hepatocellular carcinoma. Full article

The retinal vasculature provides a unique and non-invasive window into the health of the circulatory system. Josef Flammer, a pioneer in ocular vascular research, was the first to systematically describe how the state of retinal blood vessels reflects broader cardiovascular health. Because the retina is the only part of the human body where blood vessels can be visualized non-invasively, it serves as a valuable proxy for understanding microvascular conditions elsewhere, including the heart, brain, and lymphatics. Recent work has shown that retinal vasculature can be used as a proxy for microcirculatory dysfunction in other body systems, and that treatment using medical doses of vitamins can restore microcirculation, easing symptoms in disorders as diverse as glaucoma, AMD, and lymphedema without the need of pharmacological agents. The advent of machine learning tools to read retinal images promises both early detection of conditions and simplified monitoring of treatment progression. Full article

Breast cancer invasion and subsequent metastasis to distant tissues occur when cancer cells lose cell–cell contact, develop a migrating phenotype, and invade the basement membrane (BM) and the extracellular matrix (ECM) to penetrate blood and lymphatic vessels. The identification of the mechanisms which induce the development from a ductal carcinoma in situ (DCIS) to a minimally invasive breast carcinoma (MIBC) is an emerging area of research in understanding tumor invasion and metastatic potential. To investigate the progression from DCIS to MIBC, we analyzed peritumoral collagen architecture using correlative scanning electron microscopy (SEM) on histological sections from human biopsies. In DCIS, the peritumoral collagen organizes into concentric lamellae (‘circular fibers’) parallel to the ducts. Within each lamella, type I collagen fibrils align in parallel, while neighboring lamellae show orthogonal fiber orientation. The concentric lamellar arrangement of collagen may physically constrain cancer cell migration, explaining the lack of visible tumor cell invasion into the peritumoral ECM in DCIS. A lamellar dissociation or the development of small inter fiber gaps allowed isolated breast cancer cell invasion and exosomes infiltration in the DCIS microenvironment. The radially arranged fibers observed in the peri-tumoral microenvironment of MIBC biopsies develop from a bending of the circular fibers of DCIS and drive a collective cancer cell invasion associated with an intense immune cell infiltrate. Type I collagen fibrils represent the peri-tumoral nano-environment which can play a mechanical role in regulating the development from DCIS to MIBC. Collectively, it is plausible to suggest that the ECM effectors implicated in breast cancer progression released by the interplay between cancer, stromal, and/or immune cells, and degrading inter fiber/fibril hydrophilic ECM components of the peritumoral ECM, may serve as key players in promoting the dissociation of the concentric collagen lamellae. Full article

Cancer metastasis often accounts for the primary cause of cancer-related mortality, with the lymphatic system playing a pivotal role in the dissemination of malignant cells. While hematogenous vessel spread is commonly associated with distant organ metastasis, the lymphatic system serves as an early conduit for tumor cell invasion and dissemination. The process of lymphatic metastasis is a highly coordinated sequence of events that involves cancer cell invasion, intravasation into lymphatic vessels, survival, transport, and colonization of regional lymph nodes (LNs). Cancerous cells then establish micro-metastases at the colonized sites and expand in the new microenvironment, ultimately resulting in the generation of secondary tumors. Tumor-secreted factors, such as vascular endothelial growth factors (VEGF-C and VEGF-D), contribute to metastasis through lymphangiogenesis, the formation of new lymphatic vessels. In addition, cancer cells utilize pre-existing chemokine signaling pathways by expressing chemokine receptors, such as CCR7, which bind to chemokine ligands, such as CCL19 and CCL21, to facilitate targeted migration into the lymphatic vessels. LNs are often the initial sites for metastasis and therefore are indicators of distant organ involvement. It is well established that the location and extent of LN involvement provides significant prognostic information, although the optimal treatment approach for LN metastases remains a subject of debate. Understanding the mechanisms of lymphatic metastasis offers potential therapeutic targets to mitigate cancer progression. Full article

Background: Cervical cancer is a leading cause of morbidity and mortality among women globally. Currently, treatment is primarily based on tumor staging; however, discrepancies between preoperative and postoperative tumor staging remain a significant challenge and may impact treatment decisions and outcomes. This study aims to investigate the disparity between preoperative and postoperative risk factors in early-stage cervical cancer, with a particular focus on the histopathological parameters and the correlation with preclinical risk factors. Methods: Patients who underwent surgical treatment for an initial diagnosis of primary cervical carcinoma at the University Hospital Cologne in the Department of Gynecology and Obstetrics between 2015 and 2021 were included. A retrospective analysis was conducted to examine variations in histological parameters and their relationships with preclinical risk factors, such as age, BMI, smoking status, and HPV status, along with pretherapeutic diagnostic results. Results: In 85.7% of cases, preoperative grading showed concordance with postoperative grading. Postoperative upgrading was observed in 14.3% of cases with no instances of downgrading. Inconsistent findings were noted for venous invasion (3.6% of cases) and lymphovascular space invasion (6.7% of cases). No significant correlations were found between pre- and postoperative discrepancies and preclinical risk factors or pretherapeutic diagnostics. Kaplan–Meier analyses revealed no impact of discordance in grading (p = 0.559) or lymphatic vessel invasion (p = 0.752) on recurrence-free survival. Conclusions: The analyzed discrepancies were not influenced by preclinical risk factors or pretherapeutic interventions and showed no significant prognostic relevance for the patients’ recurrence-free survival. More robust conclusions would require further studies with larger sample sizes. Full article

Background: Autologous breast reconstruction has undergone a remarkable evolution, driven by the pursuit of addressing past concerns primarily related to donor site morbidity and complication risks. Improved techniques now prioritize minimizing invasiveness, complications, and recovery time while achieving aesthetically pleasing and durable results. Methods: Recent advancements in autologous breast reconstruction have been examined, focusing on enhancements in surgical techniques, imaging technologies, minimally invasive approaches, and postoperative care. Results: To reduce donor site morbidity, attention has recently shifted back to abdominal flaps vascularized by subcutaneous vessels. Specifically, the superficial circumflex iliac artery perforator (SCIP) flap has emerged as a promising option. Additionally, robotic-assisted flap harvest serves as another method to reduce the invasiveness. At the recipient site, rib-sparing internal mammary vessel isolation and perforator-to-perforator anastomosis have been suggested to lessen trauma and maintain thoracic integrity. The use of thorough preoperative imaging and intraoperative assessment of real-time perfusion with indocyanine green angiography (ICG) has enhanced the success of the procedure. Beyond aesthetic restoration, contemporary breast reconstructive surgeons are increasingly aware of both short-term and long-term complications, particularly lymphatic sequelae. The LYMPHA technique (lymphatic microsurgical preventive healing approach) promotes immediate restoration of the lymphatic system and has shown the potential to reduce the risk of breast cancer-related lymphedema (BCRL). Furthermore, the integration of enhanced recovery after surgery (ERAS) protocols has transformed perioperative care by optimizing pain management, minimizing hospitalization duration, and allowing a quicker return to daily activities. Conclusions: Recent advancements in autologous breast reconstruction have significantly improved patient outcomes. With innovations in flap design, technology, lymphatic preservation, and recovery protocols, it has been possible to usher in a new era of less invasive procedures and fewer complications while achieving high aesthetic results and allowing patients to return to their daily lives as quickly as possible. Full article

Tumor-associated macrophages (TAMs) are known to induce epithelial–mesenchymal transition (EMT) and angiogenesis in areas with a high density of accumulation in the submucosal (SM) layer. However, lymphatic vessels, which are important routes for lymph node metastasis, have rarely been analyzed, and their relationship to TAM accumulation is unknown. In this study, paraffin-embedded sections from 11 cases of human early-stage colorectal cancer (SM invasive carcinoma) were stained with CD34 antibody for vascular endothelium and podoplanin antibody for lymphatic endothelium at the deepest, central, and marginal sites of tumor invasion. Tumor blood vessels increased in the deepest invasive areas, and a positive correlation was observed between the number of TAMs and tumor blood vessels. Interestingly, lymphatic vessels with CD34-positive endothelial cells (CD34-positive lymphatic vessels) were observed within the tumor. The number of CD34-positive lymphatic vessels was significantly higher in the metastasis-positive group. These results suggest that abnormalities in the vascular and lymphatic systems are observed from the early stage of colorectal cancer development and that VEGF-A derived from TAMs is important for tumor angiogenesis. In addition, CD34-positive lymphatic vessels observed in the deepest areas of tumor invasion have not been reported in Japan, with initial reports indicating that they are neoplastic lymphatic vessels. Full article

Cancer metastasis is the leading cause of cancer-related deaths, with the ability of cancer cells to invade blood vessels or lymphatic systems, determining their metastatic potential. Therefore, the rapid and accurate assessment of cell invasiveness is crucial. Current methods, such as the Transwell assay and fluorescent labeling, are complex, invasive, and may disrupt the physiological state of live cells. In this study, we introduce an electrochemical impedance-based method for evaluating cancer cell invasiveness, combining Transwell and microfluidic technologies to monitor the invasion process in a dynamic environment. A stable microfluidic chip with 30 μm interdigital electrodes was developed, optimized for HeLa cell detection. We identified 1 kHz as the optimal frequency for achieving the maximum impedance resolution of cancer cell invasiveness. By correlating the impedance response of Z_cells/Z_no-cells with invasiveness, we established a reliable electrochemical model. This model was validated with a hydrogen peroxide cytotoxicity assay, showing a high correlation with optical staining and a minimal error of 1.89%, underscoring its potential for drug efficacy prediction. The proposed method offers rapid detection, low cost, and requires no manual intervention, making it an efficient and reliable tool for assessing cancer cell invasiveness in therapeutic research. Full article

Pigment epithelium-derived factor (PEDF) is a multifunctional soluble glycoprotein, primarily known for its potent anti-angiogenic properties. In recent years, its ability to counteract cell proliferation and motility has generated interest in PEDF as a potential tumor suppressor. In the intrahepatic Cholangiocarcinoma (iCCA), PEDF, Thrombospondin 1 (THBS1), and Thrombospondin 2 (THBS2) are expressed and released into the tumor microenvironment (TME), where they promote lymphangiogenesis at the expense of the neoangiogenic program, aiding the dissemination of cancer cells via lymphatic vessels. Recently, we demonstrated that THBS1 and THBS2 directly affect iCCA cells, exacerbating their malignant behavior, while the direct role of PEDF remains to be elucidated. In this study, through a cell-based assay and molecular analysis, we investigate the direct function of PEDF on two well-established iCCA cell lines. Our results show that PEDF affects cancer cell motility in a paracrine manner, reducing their migratory and invasive capabilities. Notably, our data suggest that the PEDF-induced inhibition of motility in iCCA cells occurs through the MAPK/ERK signaling pathway, as indicated by the reduced phosphorylation of ERK1/2. Overall, this study provides the first evidence of PEDF acting as a tumor suppressor in iCCA. Full article

A primary purpose of sleep for humans is to remove toxins and metabolic wastes from the brain (e.g., Aβ, tau, lactate) that would otherwise build up and compromise brain functionality. There are currently no drugs or devices that have been clinically shown in humans to enhance brain toxin removal, either during sleep or wakefulness. This perspective article focuses on a recently (re)discovered major route of toxin drainage from the human brain through meningeal lymphatic vessels (mLVs) and the primary enhancer of their flow—the cytokine Vascular Endothelial Growth Factor (VEGF). The purpose of this perspective article is to present pre-clinical and clinical evidence relevant to a new bioengineered technology (Transcranial Radiofrequency Treatment; TRFT) that appears to enhance mLV flow to increase brain toxin cleansing in humans during wakefulness. In being both safe and non-invasive, TRFT is administered in-home, presently through a device called “MemorEM”. Two months of daily TRFT during wakefulness increased the typically low plasma/brain levels of VEGF in Alzheimer’s Disease (AD) subjects, which was associated with increased Aβ and tau toxin removal from their brains during wakefulness—ostensibly through VEGF-increased mLV flow. Even irrespective of baseline VEGF levels, brain toxin cleansing was increased by TRFT in AD subjects, who also experienced a notable reversal of their cognitive impairment after TRFT. Additional clinical studies are nonetheless required to firmly establish TRFT’s brain cleansing abilities during wakefulness. In performing a major duty of sleep, TRFT during wakefulness is proposed as a viable intervention to counter the decline in nighttime brain toxin cleansing that occurs with aging and in multiple brain diseases, most notably Alzheimer’s Disease. The implications of TRFT for insomnia and for sleep deprivation are also discussed, as is the potential for TRFT to extend healthy human longevity. Full article

High levels of vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF)-2 and angiopoietin (ANG)-2 are found in tissues from oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMDs). As might be expected, VEGF, FGF-2, and ANG-2 overexpression parallels the development of new blood and lymphatic vessels that nourish the growing OPMDs or OSCCs and provide the latter with metastatic routes. Notably, VEGF, FGF-2, and ANG-2 are also linked to the epithelial-to-mesenchymal transition (EMT), a trans-differentiation process that respectively promotes or exasperates the invasiveness of normal and neoplastic oral epithelial cells. Here, we have summarized published work regarding the impact that the interplay among VEGF, FGF-2, ANG-2, vessel generation, and EMT has on oral carcinogenesis. Results from the reviewed studies indicate that VEGF, FGF-2, and ANG-2 spark either protein kinase B (AKT) or mitogen-activated protein kinases (MAPK), two signaling pathways that can promote both EMT and new vessels’ formation in OPMDs and OSCCs. Since EMT and vessel generation are key to the onset and progression of OSCC, as well as to its radio- and chemo-resistance, these data encourage including AKT or MAPK inhibitors and/or antiangiogenic drugs in the treatment of this malignancy. Full article

Indocyanine Green (ICG) has significantly advanced minimally invasive surgery. It is widely recognized for its ability to visualize blood vessel patency in real-time across various surgical specialties. While its primary use in colorectal surgery is to evaluate anastomoses for leaks, numerous other applications have been documented in the literature. In this review, we aim to explore both established and emerging applications of ICG fluorescence in colorectal surgery, with the goal of improving patient outcomes. This includes preoperative tumor marking and the detection of metastatic disease. Some applications, such as lymphatic mapping, require further research to determine their impact on clinical practices. Conversely, others, like the intraoperative localizations of ureters, necessitate additional procedures and are not yet widely accepted by the surgical community. However, the development of alternative compounds could offer better solutions. Future research should focus on areas like quantitative ICG and protocol standardization in prospective multicenter studies. Full article

We studied 115 cases of EEC diagnosed on hysterectomy specimens. Double immunohistochemical staining (D2-40/CD31) was performed in all 115 cases to show LVI and BVI on the same slide. MELF pattern invasion was present in 24/115 (21%) cases. MELF-positive tumors had a higher frequency of LVI than MELF-negative tumors (58% and 23%, respectively); the frequency of BVI was twice as high in MELF-positive tumors in comparison to MELF-negative tumors (25% and 12%, respectively). These differences were significant (p ˂ 0.0001). All tumors with positive BVI also had a concomitant LVI. The presence of MELF invasion had no impact on overall survival, confirming previous studies. 5-year survival rates were almost equal in cases with negative LVSI and cases with positive isolated LVI (98% vs. 97%). However, in cases where BVI was also present, the 5-year survival rate was significantly lower, 63% (p ˂ 0.0001). Furthermore, BVI proved to be an independent prognostic factor for overall survival, disease-free survival, and recurrence in the multivariate analysis. In conclusion, MELF pattern invasion is a good predictor of lymphatic and blood vessel invasion but has no prognostic value. Our results suggest that BVI in EEC has greater clinical value than isolated LVI or myometrial invasion patterns, and the therapeutic approach should be guided by BVI presence. Therefore, we hope this study will promote the routine evaluation of BVI in the context of EEC diagnostic procedures. Full article

Congenital cervicofacial vascular anomalies are extremely rare and present many difficulties in diagnosis and treatment requiring a multidisciplinary approach. Firstly, there is little consensus on this subject among head and neck specialists. There are two main types of vascular anomalies: vascular tumors and vascular malformations. Vascular malformations are also divided into malformations with slow blood flow (veins, lymphatics, capillaries or combined) and malformations with a fast blood flow (arteriovenous malformations and fistula). Vascular tumors like hemangiomas are known for their spontaneous involution with aging, while vascular malformations grow in dimensions with age. It is very important to choose the correct differential diagnosis between cervicofacial hemangiomas and vascular malformations for proper therapy management. Anamnesis and clinical exams help in raising suspicions about the real nature of a cervico-vascular anomaly. Furthermore, imaging brings in-depth details of the anomaly, ranging from ultrasound and contrast CT to MRI scanning and minimally invasive angiography. Angiography with selective embolization is rarely a curative procedure for arteriovenous malformations, being more suitable as a preliminary step before attempted surgical removal. Surgery is clearly necessary when there are aesthetic and functional deficits. Slow-flow vascular malformations present a reduced morbidity, and in cases without involution, the surgical ablation is reserved for the cases with aesthetic dysfunctions or psychological trauma. Lymphatic malformations must undergo surgical ablation when they are associated with mass effects and compression of great vessels or aerial viscera. The prognosis after surgical removal is good, with a low rate of recurrence or morbidity. Fast-flow vascular malformations require a combined approach, with embolization and excision in the next 48 h for safety reasons. Removal may be followed by reconstructive surgery depending on the location and dimensions of the malformation, with a possible secondary recovery of the normal microscopic vessels. Some of the masses may hinder the normal airflow and swallowing. Pathology is the gold standard for confirming the clinical and imaging diagnosis. Full article