Aberrant Vessels Research Articles

Jejunal Dieulafoy's lesion - An exceptionally rare and challenging culprit of gastrointestinal bleeding.

A 78-year-old male presented to the emergency department with melena. He was hemodynamically stable but displayed a hemoglobin level of 5.8g/dL necessitating blood transfusion. Initial esophagogastroduodenoscopy and colonoscopy failed to identify a bleeding source, prompting a capsule endoscopy that revealed an active bleeding site in the jejunum. A single-balloon enteroscopy identified an aberrant vessel in the mid-jejunum protruding through a 3mm mucosal defect, devoid of surrounding inflammation, consistent with a Dieulafoy's lesion, in which two through-the-scope clips were applied. Despite this, ongoing melena and decreasing hemoglobin levels in the subsequent days led to a second single-balloon enteroscopy, which confirmed continued bleeding. Definitive hemostasis was achieved through diluted adrenaline injection, four additional through-the-scope clips, and polidocanol sclerotherapy. Jejunal Dieulafoy's lesion is extremely rare and presents notable diagnostic and therapeutic challenges. Ávila et al. recently reported a case where, despite capsule endoscopy identifying the bleeding site, single-balloon enteroscopy failed to confirm the diagnosis, leading to the use of motorized enteroscopy with argon and metallic clip treatment. Similarly, our experience highlights the diagnostic value of capsule endoscopy and the crucial role of device-assisted enteroscopy in a multimodal therapeutic approach, which was essential for achieving successful hemostasis.

First-trimester uterine artery Doppler and PAPP-A levels as predictors of pre-eclampsia in a South Asian population; Mardan city, Pakistan

One of the most common causes of maternity and neonatal fatalities and mortality is Pre-eclampsia (PE) which is responsible for 14% of global maternal deaths. The condition is primarily attributed to impaired trophoblastic invasion, which increases uterine artery pulsatility index (PI). A predictive analysis was done at Swat Medical College and Women's Hospital in Mardan, Pakistan from June 2022 to June 2023, including 218 pregnant women aged 11-13+6 weeks. Females with multifetal pregnancies, congenital fetal anomalies, and pre-existing medical conditions were excluded from this research. Uterine artery the Doppler and the PAPP-A testing were done to screen the conditions. Of 624 screened women, 218 were included in the final analysis using SPSS. The study population's mean age was 28 years, with 59% primiparous and 41% multiparous women. The incidence of PE was 35.5%, and gestational hypertension was 22.5%. Women developing hypertensive disorders had significantly higher mean uterine artery PI (2.11) compared to normotensive women (1.21, p=0.01), and significantly lower mean PAPP-A MoM levels (0.78 vs. 1.42, p<0.001). Coupled aberrant uterine blood vessels PI and PAPP-A predicted PE with high significance (p<0.001). Uterine artery in the first trimester Doppler and PAPP-A levels are effective in predicting pre-eclampsia in a South Asian population. Implementing these screenings could enhance early detection and management of PE, potentially reducing associated morbidity and mortality.

Abstract B074: Aberrant pericytes in PDAC: effects on endothelial-pericyte adhesion, vascular integrity, and tumor microenvironment

Abstract Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in men and women in the U.S., with a 5-year survival rate of 13%. Within the PDAC tumor microenvironment (TME), morphologically aberrant leaky vessels are responsible for hypoxia and impaired immune response, which likely reduces the efficacy of cancer therapies. We and others showed that pericyte (PC) coverage significantly correlates with vascular integrity, function, and intratumor hypoxia. Therefore, understanding the contribution of abnormal PC to the TME evolution is a critical step toward PDAC treatment options. Consequently, we hypothesize that correcting such undesirable phenotype via vascular normalization will enhance treatment efficacy. Our study revealed that tumor-associated pericytes across all PDAC tumor tissues exhibited ectopic alpha-smooth muscle actin (αSMA) cytoskeletal protein expression up to 10 times higher than normal pericytes, which was significantly correlated with vascular leakiness and hypoxia. Our previous publication showed that PDAC-derived extracellular vesicles are potent inducers of αSMA expression in pericytes characterized by biomechanical abnormalities. To evaluate the vascular functional defect, we performed a tube formation assay showing abnormal pericytes contribute to abnormal vasculatures in vitro. Our investigation aims to uncover the cause of the abnormal pericyte phenotype that disrupts the physical adhesion between pericytes and endothelial cells (EC), resulting in compromised vasculature. Our findings reveal consistently upregulated monocarboxylate transporters in vascular cells. To enhance EC-pericyte adhesion, we investigated lactate metabolic communication, which is tightly linked due to the proximity of ECs and pericytes. We have shown that in PDAC, MCT1 lactate exporters are upregulated in EC. Conversely, MCT12 lactate importers are highly expressed in pericytes. The high amount of lactate produced by ECs decreases the pH in the basement membrane. So, we knocked down MCT1 transporters in ECs to increase basement pH, leading to improved PC-EC attachment and pericyte homeostasis. Finally, we performed single-cell RNA sequencing to determine the pathological signature of tumor pericytes and identify potential target molecules for vascular normalization. In conclusion, our study indicates that tumor-associated pericytes undergo phenotype switching and disturbed metabolic communication under the influence of pancreatic cancer cells. These aberrant pericytes might contribute to non-optimal vascular integrity and function. Single-cell RNA sequencing helped understand the molecular signature of the PDAC pericyte, providing a powerful tool to develop novel targeting strategies for vascular normalization. Future work includes exploring the vascular normalization approach by suppressing pericyte phenotype switching to enhance vascular function and chemo- and immunotherapeutic efficacy. Citation Format: Vikneshwari Natarajan, Sangdeuk Ha, Jiha Kim. Aberrant pericytes in PDAC: effects on endothelial-pericyte adhesion, vascular integrity, and tumor microenvironment [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr B074.

BILIARY DUCTAL PLATE MALFORMATION WITH SECONDARY PORTAL HYPERTENSION AND MULTIPLE ACQUIRED SHUNTS IN A LITTER OF AMUR TIGERS (PANTHERA TIGRIS ALTAICA).

Congenital abnormalities in tigers (Panthera tigris) are infrequently reported but have included ectrodactyly, cataracts, and vestibular disease. Primary hepatic disease has been documented in multiple nondomestic felid species but is considered uncommon in tigers. To the authors' knowledge, there are no previous reports of congenital abnormalities of the liver in tigers. In May 2022, two male Amur tiger cubs (Panthera tigris altaica) were born at a zoological institution via cesarean section to address dystocia, following the natural birth of a female cub. Between two and six months of age, all three cubs developed progressive lethargy, inappetence, and neurological signs consistent with hepatic encephalopathy, including obtundation and ataxia. In all three cases, serum biochemical values revealed progressive, marked elevations in hepatic enzyme levels with reduction in hepatic synthetic products (albumin, urea, cholesterol). Computed tomographic imaging showed a large cluster of aberrant tortuous vessels craniomedial to the left kidney in all three tigers, consistent with acquired extrahepatic portosystemic shunts. Histologic examination of the livers identified biliary ductal plate malformations. This report details the presentation, clinical findings, diagnoses, and therapeutic interventions attempted in three Amur tiger cubs with biliary ductal plate malformation and subsequent portal hypertension with multiple acquired portosystemic shunts, an unusual abnormality not previously reported in non-domestic felids.

Laparoscopic retrocaval ureteroplasty in a child with combined urodynamic disorders

Retrocaval location of the ureter in combination with aberrant renal vessels is a rare and complex urinary system malformation that requires careful verification. Currently, the most appropriate method for diagnosing retrocaval ureter is contrast-enhanced computed tomography. With the development of hydronephrosis or ureterohydronephrosis, the patient underwent laparoscopic ureteroplasty. Surgical treatment of retrocaval ureter involves resection of the altered ureter or pelvic–ureter segment with the formation of uretero-ureteral anastomosis or ureteropieloanastomosis anterior to the inferior vena cava. This article presents a successful laparoscopic ureteroplasty in a child with complex urodynamics of the urinary tract. Considering the presence of two levels of ureteral vascular crossing in the clinical example, pyelo-ureteral segment was performed to relocate the ureter in front of the inferior vena cava and aberrant inferior polar vessels. The patient was discharged in satisfactory condition to the outpatient stage of treatment, with subsequent hospitalization in the urological department. Retrocaval location of the ureter in combination with aberrant renal vessels is a rare congenital anomaly that requires prompt examination in a specialized clinic and an individual examination and treatment plan.

366 A Case Study: Application of Personalised External Aortic Root Support to Overcome a Failing Ross Procedure

Abstract Aortic root aneurysms are traditionally treated by aortic root replacement surgery alone or in combination with aortic valve replacement in a Modified Bentall procedure. We present a novel surgical approach using a Personalised External Aortic Root Support (PEARS) in the management of an aortic root aneurysm in a 24-year-old male, initially presenting in infancy with mixed aortic valve disease who underwent a free root Ross procedure in 2010 aged 11. Follow-up cardiac magnetic resonance imaging and transthoracic echocardiography showed mild aortic and pulmonary valve regurgitation with aortic root dilatation (51mm). In 2022, Computerised tomography (CT) exhibited dilation of the Sinus of Valsalva (43mm) and ascending aorta (56 mm). MDT review deemed redo valve-sparing root replacement appropriate as the ascending aorta was >55mm with an approximate 8mm increase over three years. As the young patient wished to avoid warfarinisation and the autograft valve maintained good function, a reduction PEARS was considered. In September 2023, a reduced aortic PEARS graft (80% reduction) was implemented along with a redo of the right ventricle to pulmonary artery conduit. Whilst applying the PEARS it was noted that there was a retroaortic circumflex artery, care was taken to mobilise this aberrant vessel to avoid compression by the graft. Cardiopulmonary bypass and cross-clamp times were 180 and 116 minutes respectively. Intraoperative transoesophageal echocardiography confirmed good bi-ventricular function with no pulmonary regurgitation additionally on postoperative CT the aortic diameter was 38mm. In conclusion, application of a reduction PEARS is a potential alternative to a valve-sparing aortic root replacement method in young patients.

Aneurysmal artery supplying pulmonary sequestration: successful combined approach.

A 62-year-old man was diagnosed with an asymptomatic intralobar pulmonary sequestration supplied by a short-neck proximal 57×25 mm aneurysmal artery originating from the mid-descending aorta. The patient underwent thoracic endovascular aneurysm repair; an aortic endograft was released to entirely restore the aberrant vessel. Then, pulmonary resection was performed. A triportal video-assisted left lower lobectomy was carried out. The thoracic endovascular aneurysm repair minimized the risk of bleeding and allowed a safe pulmonary resection with a minimally invasive approach.

Extralobar sequestration — not obvious radiologic finding. Illustrated overview. Case report

INTRODUCTION: Bronchopulmonary sequestration is a rare congenital pulmonary malformation. A sequestration is generally defined as non-functioning lung tissue that is not in normal continuity with the tracheobronchial tree and derives its blood supply from systemic vessels. OBJECTIVE: To define the main clinical and radiologic features of intra- and extralobar sequestration of the lung, to study vessel variability and to analyse case of not obvious CT images of intralobar sequestration that was diagnosed intraoperatively. MATERIALS AND METHODS: We analysed literature found in PubMed and ScienceDirect regarding lung sequestration since 1979. The case report of a patient with extralobar sequestration diagnosed intraoperatively.RESULTS: The main clinical and radiologic features of lung sequestration, challenges of differential diagnosis were summarised, including specificity of case report.DISCUSSION: Presence of aberrant vessel requires verification of pathology before operation due to high risk of haemorrhage. The leading role in the verification belongs to radiologic imaging, however in rare cases aberrant vessel may not be visualised due to small diameter or occlusion.CONCLUSION: The anatomy of aberrant vessels in sequestrations is extremely variable. In case report sequestration was seen in an adult. The pathology was not diagnosed prior to the operation due to failure of the vessel visualisation. Knowledge of possible diagnostic challenges decreases the risk of intraoperative complications.

Abstract LB309: Influence of pathological pericytes on PDAC tumor progression and tumor microenvironment

Abstract Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer death in men and women in the U.S., with a 5-year survival rate of 12 %. This poor prognosis is partly due to the aggressive nature of the disease, lack of early detection methods, its complex and dense tumor microenvironment (TME), and lack of effective treatment options. Within the PDAC TME, morphologically aberrant leaky vessels are responsible for hypoxia and impaired immune response, which likely reduces the efficacy of cancer therapies. We and others showed that pericyte coverage significantly correlates with vascular integrity/function and intratumoral hypoxia. Therefore, understanding perivascular heterogeneity and the unique contribution of each phenotype to the TME evolution is a critical step toward personalized treatment options for PDAC. Consequently, we hypothesize that correcting such undesirable phenotype via vascular normalization will alleviate the harsh TME and enhance the treatment efficacy. Our study revealed that tumor-associated pericytes across all PDAC tumor tissues exhibited ectopic αSMA expression up to 10 times higher than normal pericytes. This aberrant pericyte phenotype correlated with vascular leakiness, hypoxia, and vessel leakiness. Our attempt to elucidate the underlying mechanism of pericyte phenotype switching using an in-vitro culture system shows that pancreatic cancer cell-derived extracellular vesicles are a potent inducer of αSMA expression in pericytes present mechanical abnormalities and immune-suppressive features. To further determine the pathological signature of tumor pericytes and identify potential target molecules toward vascular normalization, we performed single-cell RNA sequencing (scRNA-seq). Pericytes were isolated from WT pancreas and KPC tumors at 15-20 weeks to obtain desired viable single-cell population suitable for 10x library preparation and Illumina sequencing.We isolated and barcode at least 5000 cells using the 10X genomics system. Sequencing libraries were prepared using the Chromium Single Cell 3ʹ reagent kit v3. They were sequenced until a sequencing depth of 100,000 reads per cell was achieved, and the data was analyzed using Cell Ranger and various other analytical tools (e.g., Seuret, Conos, ScMerge, singleR). We generated custom scripts from the single-cell data to answer the relevant questions. Sequences were demultiplexed based on barcodes and assigned unique molecular identifiers (UMIs). We visualized clusters using graphing methods, such as t-SNE plots and UMAP clustering. This approach helped identify groups of cells with unique and differential transcriptional landscapes and group them into cellular subtypes based on their gene expression profiles. In conclusion, our study indicates that tumor-associated pericytes undergo phenotype switching under the influence of pancreatic cancer cells, and these aberrant pericytes might contribute to non-optimal vascular integrity and function. Single-cell RNA sequencing helped understand the molecular signature of the pericyte subpopulation, providing a powerful tool to develop novel targeting strategies for vascular normalization. Future work includes exploring the vascular normalization approach by suppressing pericyte phenotype switching to enhance vascular function and chemo and immunotherapeutic efficacy. Citation Format: Vikneshwari Natarajan, Sangdeuk Ha, Jiha Kim. Influence of pathological pericytes on PDAC tumor progression and tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB309.

An anatomical study on the variations and clinical significance of the corona mortis within a South African sample

IntroductionAnterior orthopaedic approaches, much like the Modified Stoppa approach, target fractures of the anterior column of the pelvis and acetabulum. The approach is described as a minimally invasive technique that may lead to iatrogenic haemorrhage and fatality in patients. Such mortality is due to the inadvertent severing of the corona mortis vessels, a clinical term referring to the anastomosis between the obturator vessels and the external iliac vessels typically via an accessory obturator vessel that courses over the pelvic brim. Knowledge regarding the prevalence and clinical significance of the corona mortis, especially within the South African population is lacking, and therefore further investigation of this anomaly is necessary. Materials and methodsThis study investigated the incidence and variations of the corona mortis vessels in a South African sample using 63 adult cadavers obtained from the Department of Anatomy, University of Pretoria. After careful dissection of the blood supply to the pelvis, the prevalence of corona mortis was investigated. Variations regarding the composition of the corona mortis and the incidence of aberrant obturator vessels were documented. ResultsThe incidence of corona mortis was observed in 67.5% of the study sample, with 91.6% being venous and 8.4% being arterial in composition. An incidence of 26.0% of aberrant obturator arteries and 8.1% of aberrant obturator veins were observed originating or draining directly into the external iliac system, respectively. A single rare instance of corona mortis was observed and involved an anastomosis with the superior vesical vein rather than the typical obturator vein. While variations amongst anomalous accessory vessels were observed which resulted in as many as 3 aberrant vessels coursing over the pelvic brim. No significant difference was concluded for the incidence of corona mortis between the left and right sides or between males and females. ConclusionMapping out the parameters of the corona mortis and examining the variation linked with the anomaly will aid orthopaedic surgeons in implementing anterior approaches with reduced vascular damage and iatrogenic deficit. Further understanding of its incidence in the South African population will in turn assist in interpreting its clinical significance.

Correlation Diagnostic Contribution of SPECT/CT Imaging to 99mTc-DTPA Dynamic Scintigraphy in Patients with Different Renal Pathologies

Introduction: Dynamic renal scintigraphy with 99mTechnetium diethylenetriaminepentaacetic acid (99mTc-DTPA) is a widely performed imaging method to evaluate kidney function of patients with various renal pathologies. However the one-stop-shop combination with subsequent SPECT/CT imaging is a rarely discussed topic. Objective: The aim of the study was to evaluate the diagnostic benefits of SPECT/CT imaging to 99mTc-DTPA dynamic renal scintigraphy. Materials and Methods: A group of 32 patients (21 females and 11 males) who underwent dy- namic nephroscintigraphy with subsequent SPECT/CT was retrospectively studied. A dose of 185MBq (5mCi) 99mTc-DTPA was intravenously applied. A low-dose non-contrast CT protocol was used for attenuation correction and anatomical correlation. Results: Impaired relative renal function in various degrees of left kidney was detected in 18 patients (56%) and of right kidney in 14 patients (44%). SPECT/CT imaging identified the particular cause for the renal dysfunction in the analyzed subjects. The hybrid imaging demonstrated urolithiasis in 11 patients, postoperative ureteral strictures in 5 patients, diagnosed urological cancer in 4 patients and external compression of ureter in 2 patients as a possible obstructive cause. Congenital renal anomalies were the identified causes of impaired renal function in 10 patients – hypoplastic kidney in 4 patients, duplex kidney in 2 patients, multiple cortical cysts in 2 patients, aberrant vessel obstructing the pyeloureteral segment in 1 patient and horseshoe kidney in 1 patient. Conclusion: Dynamic renal scintigraphy combined with SPECT/CT is a very useful clinical tool, by providing not only functional but also anatomical information of the urinary tract, especially in the evaluation of obstructive uropathies and congenital renal abnormalities, that has the potential to change clinical management.

The Incidence and Variation of Corona Mortis in Multiracial Asian: An Insight from 82 Cadavers.

Corona Mortis (CMOR) is a term used to describe an anatomical vascular variant of retropubic anastomosis located posterior to superior pubic ramus. We aim to provide sufficient data on the incidence, morphology and mean location of 'crown of death' in Asian population. Other objectives include to assess the relationship between CMOR incidence with gender, race and age. This is a cross-sectional cadaveric study involving 164 randomly selected fresh multiracial Asian hemipelves (82 cadavers). Hemipelves were dissected to expose and evaluate the vascular elements posterior to superior pubic rami. Data were analysed using Chi-Square, t-test and with the help of IBM SPSS Statistics v26 software. CMOR was found in 117 hemipelves (71.3%). No new morphological subtype was found. The mean distance of CMOR to symphysis pubis was 54.72mm (SD 9.35). Based on the results, it is evident that precaution needed to be taken at least within 55mm from symphysis pubis during any surgical intervention. The lack of statistically significant correlation between CMOR occurrence and gender, race and age suggest that the incidence of CMOR could be sporadic in manner. We conclude that CMOR is not just aberrant vessel as the incidence is high and this finding is comparable to other studies. The mean location of CMOR obtained in this study will guide surgeons from various disciplines in Asia to manage traumatic vascular injury and to perform a safe surgical procedure involving the pelvis area.

Targeting PKM2 signaling cascade with salvianic acid A normalizes tumor blood vessels to facilitate chemotherapeutic drug delivery

Aberrant tumor blood vessels are prone to propel the malignant progression of tumors, and targeting abnormal metabolism of tumor endothelial cells emerges as a promising option to achieve vascular normalization and antagonize tumor progression. Herein, we demonstrated that salvianic acid A (SAA) played a pivotal role in contributing to vascular normalization in the tumor-bearing mice, thereby improving delivery and effectiveness of the chemotherapeutic agent. SAA was capable of inhibiting glycolysis and strengthening endothelial junctions in the human umbilical vein endothelial cells (HUVECs) exposed to hypoxia. Mechanistically, SAA was inclined to directly bind to the glycolytic enzyme PKM2, leading to a dramatic decrease in endothelial glycolysis. More importantly, SAA improved the endothelial integrity via activating the β-Catenin/Claudin-5 signaling axis in a PKM2-dependent manner. Our findings suggest that SAA may serve as a potent agent for inducing tumor vascular normalization.

Case report of a type II single umbilical artery seen in the first trimester anomaly scan

Umbilical arteries normally originate from a pair of allantoic arteries. Obliteration or non-formation of any of the two umbilical arteries gives rise to a single umbilical artery (SUA). 0.5–1% of fetuses show the presence of a SUA. A rarer abnormality is when a SUA is found originating from the abdominal aorta, representing the persistent vitelline artery. Such an anomaly is termed Type II SUA. Here, we present a case of Type II SUA in a 30-year-old first trimester gravid female. Obstetric ultrasound done in the first trimester showed non-visualization of the umbilical arteries adjacent to the urinary bladder. Instead, an aberrant, large vessel was seen tracking anteriorly from the aorta towards the umbilical cord. The aorta distal to the origin of this aberrant vessel appeared hypoplastic.

Abnormal retinal vessel filling in central retinal artery occlusion

ABSTRACT Clinical relevance Central retinal artery occlusion (CRAO) is an ophthalmic emergency with a poor prognosis. Several initial CRAO presentation factors can influence the final visual outcome. Fluorescein angiography filling of retinal vessels in CRAO has not been studied in great detail. Background The aim of this paper is to study the aberrant filling of the retinal vessels on fluorescein angiography in patients with CRAO and understand its clinical relevance. Methods Cases of CRAO diagnosed between June 2017 and May 2022 and who had undergone a fundus fluorescein angiography were included. Comparisons were made between the cases with and without aberrant filling of the retinal vessel. Results Twenty-two eyes of 22 patients (14 males and 8 females) with CRAO underwent fluorescein angiography. Ages of the patients ranged from 18 to 73 years, while time interval between development of acute onset vision problems and presentation to the retinal clinic ranged from a minimum of 1 day to a maximum of 30 days. Snellen visual acuity at presentation ranged from perception of light (PL +) to 6/6. On fluorescein angiography, aberrant flow of the fluorescein dye into the retinal vein was observed in four of the 22 (18%) eyes with CRAO. All these cases showed a patient's temporal cilioretinal artery. The cases with aberrant filling of the retinal vessels showed a better presenting visual acuity (6/6–6/60), lesser severity of inner retinal damage and a better final visual acuity (6/6–6/60) compared to CRAO cases without aberrant filling. Conclusion Aberrant filling of the retinal vein can be seen on fluorescein angiography in eyes with CRAO and a patent temporal cilioretinal artery. Such eyes with aberrant retinal vessel filling have a better visual prognosis.

Deciphering hepatoma cell resistance to tyrosine kinase inhibitors: insights from a Liver-on-a-Chip model unveiling tumor endothelial cell mechanisms.

Liver cancer represents a significant global burden in terms of cancer-related mortality, with resistance to anti-angiogenic drugs such as Sorafenib and Lenvatinib presenting a formidable challenge. Tumor angiogenesis, characterized by the formation of new blood vessels within tumors, plays a pivotal role in cancer progression and metastasis. Tumor endothelial cells, specialized endothelial cells lining tumor blood vessels, exhibit unique phenotypic and functional traits that drive aberrant vessel formation and contribute to therapy resistance. CD105, a cell-surface glycoprotein that is highly expressed on endothelial cells during angiogenesis, including tumor endothelial cells, regulates endothelial cell proliferation, migration, and vessel formation by modulating transforming growth factor-beta (TGF-β) signaling pathways. Elevated CD105 expression on tumor endothelial cells correlates with increased angiogenic activity and poor prognosis in cancer patients. Targeting CD105 with antibodies presents a promising strategy to inhibit tumor angiogenesis and disrupt tumor vasculature, offering potential therapeutic benefits by interfering with the tumor microenvironment and inhibiting its progression. This study investigates tumor angiogenesis through a three-dimensional (3D) microfluidic co-culture system incorporating endothelial cells and hepatocellular carcinoma (HCC) cells. The primary focus is on the role of CD105 expression within the liver tumor microenvironment and its contribution to increased chemoresistance. Additionally, this research examines the influence of CD105 expression on the efficacy of tyrosine kinase inhibitors (TKIs) and its pivotal function in facilitating angiogenesis in liver tumors. The proposed microfluidic chip model investigates liver cancer cell interactions within a microfluidic chip model designed to simulate aspects of liver tumor angiogenesis.

Prenatal diagnosis and postnatal outcome of Type-III vasa previa: systematic review of literature.

Type-III vasa previa (VP) is a rare form of VP, not necessarily associated with other placental or vascular anomalies, in which aberrant vessels run from the placenta to the amniotic membranes, near the internal cervical os, before returning to the placenta. Early diagnosis of Type-III VP is important but technically challenging. The objective of this study was to gather the current available evidence on the perinatal diagnosis and outcome of Type-III VP. A systematic review of the literature on the perinatal diagnosis of atypical Type-III VP was carried out in PubMed, MEDLINE and EMBASE accordingto PRISMA guidelines from inception to March 2023. Data extraction and tabulation were performed by two operators and checked by a third senior author. The quality of the included studies was evaluated using the National Institutes of Health tool for the quality assessment of case-series studies. Our local ultrasound database was searched for previously unreported recent cases. Characteristics of prenatally and postnatally diagnosed Type-III VP, including clinical features and perinatal outcomes, were summarized using descriptive statistics. Eighteen cases of Type-III VP were included, of which 16 were diagnosed prenatally (14 cases were retrieved from 10 publications and two were unpublished cases from our center) and two were diagnosed postnatally (retrieved from two publications). All prenatal cases were diagnosed on transvaginal ultrasound at a mean gestational age of 29 weeks (median, 31 weeks; range, 19-38 weeks). Conception was achieved with in-vitro fertilization in 4/16 (25.0%) cases. There were no prenatal symptoms in 15/18 (83.3%) cases, while in two (11.1%) cases there was vaginal bleeding and in one (5.6%) preterm labor occurred. In 15/18 (83.3%) cases, at least one placental abnormality was observed, including low-lying insertion (9/17), succenturiate or accessory lobe (1/17), velamentous cord insertion (3/18) and marginal insertion (9/18). All prenatally diagnosed cases were liveborn and were delivered by Cesarean section before rupture of membranes at a median gestational age of 35 weeks (range, 32-38 weeks) without neonatal complications. Emergency Cesarean section was performed in 2/16 (12.5%) cases with a prenatal diagnosis and 1/2 (50.0%) cases with a postnatal diagnosis (P = 0.179). Among those with data available, an Apgar score of ≤ 7 was observed in the prenatally vs postnatally diagnosed group in 5/13 vs 1/1 cases, respectively, at the 1-min evaluation and 3/13 vs 1/1 cases, respectively, at the 5-min evaluation. The prenatal diagnosis of Type-III VP is challenging, with few cases reported in the literature; however, it is crucial for minimizing the risk of adverse outcome by enabling early-term elective Cesarean delivery prior to rupture of membranes. Given that clinical manifestations and risk factors are non-specific, and that Type-III VP cannot be excluded when there is a normal cord insertion or a singular placental mass, systematic screening by transvaginal ultrasound in the general pregnant population is recommended, particularly in those with a low-lying or morphologically abnormal placenta and those who conceived using assisted reproductive technology. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

RESTORE VISION: Novel advanced and repurposed therapeutics for vision restoration in a group of severe rare ocular diseases – Short introductory talk

Rare Eye Diseases (REDs) collectively represent a major cause of visual impairment and blindness for children and young adults in Europe. But importantly, REDs also affect adults and the aging population. Defective wound healing at the cornea and ocular surface, excessive inflammation, nerve degeneration, stem cell dysfunction, and aberrant vessel ingrowth are the common denominators in many REDs, representing a critical medical problem and an area of unmet medical need. The onset and progression of many REDs are characterized by common pathophysiologic mechanisms. The goal of many research groups is to disrupt these aberrant mechanisms with the aim of making therapy more effective. Current management is often prohibitively expensive, has low efficacy and leads to debilitating side effects, pointing to a critical medical problem and area of unmet medical need.Here, we will briefly introduce the RESTORE VISION project, which has been recently funded by the European Commission and brings together actors from across the full value chain: 6 leading research institutions, 3 SMEs and a European patient organization. The project will take a ground‐breaking approach to improve eye health by verifying disease pathomechanisms, using cutting‐edge models for each rare disease to test novel and repurposed compounds and determine drug mechanisms of action, formulating compounds as safe eye drop suspensions or subconjunctival drugs, and performing several first‐in‐human trials of novel therapies.

Retrospective analysis of patients with Dieulafoy’s lesions

Background and Aims: Gastrointestinal bleeding is an emergent condition in clinical practice. Early diagnosis and proper treatment of the lesion is essential. Dieulafoy's lesion is an aberrant submucosal vessel eroding surrounding mucosa. These lesions cause of 1-2% of all gastrointestinal bleedings. Here we report cases with Dieulafoy's lesion presenting with upper gastrointestinal bleeding. Materials and Methods: Through a time frame of between August 2017-August 2021, patients admitted to our hospital presenting with upper gastrointestinal bleeding and diagnosed as Dieulafoy’s lesion were included in the study. Patients' files were screened retrospectively. Results: The study included 30 patients with a mean age of 65.9 ± 18.2 (20 - 92) years. Half of them were female. The most observed presentations were melena, hematemesis, and hematochezia. Associated diseases were hypertension, atherosclerotic heart disease and diabetes mellitus. In 26 (86.7%) patients, Dieulafoy's lesion was diagnosed in first endoscopy, while in four patients Dieulafoy's lesion was diagnosed in second endoscopy. Time interval between hospital admission to first endoscopy was 3.1 ± 2.5 (1 - 10) hours. In 23 patients Dieulafoy's lesion was in the stomach and in 6 patients in duodenum and in 1 patient in esophagus. Endoscopic therapy was applied to all patients. The most applied treatment modality was sclerotherapy + hemoclip application. One patient had required surgery due to recurrent bleeding. Six patients died. Three of them was bleeding related. Conclusion: Dieulafoy's lesion is a rare but serious cause of gastrointestinal bleedings. Early diagnosis and proper treatment is important. Patients may need repeated endoscopy for diagnosis. Hemoclip application is cheap, easy, safe, and effective treatment modality with/without sclerotherapy.

Robot-assisted transposition of aberrant lower polar renal vessels in a 14-year-old child with vasorenal hydrophnerosis

This study presents a patient with pyeloureteral segment obstruction caused by aberrant inferior polar vessels using the robotic Hellström – Chapman procedure and reports its short-term results. A 14-year-old girl was admitted to Irkutsk Regional Children’s Clinical Hospital because of obstruction of the pyeloureteral junction caused by external compression by aberrant lower polar vessels. The diagnosis was established by ultrasonography and Doppler sonography and confirmed by contrasted computed tomography. Surgery was performed using the Versius surgical robot manufactured by CMR (UK). Delicate actions were used to mobilize the abnormal vessels and move them to the anterior wall of the pelvis. Then, they were “wrapped” with the anterior wall of the pelvis. Postoperative follow-up included clinical evaluation and renal ultrasound examination 1, 3, and 6 months after surgery. The operative duration was 65 min. During the robot-assisted Hellström – Chapman operation, no intraoperative complications, such as damage to the vessels supplying the kidney and neighboring organs, were noted. The patient did not require internal or external drainage of the upper urinary tract or perinephric space. The anteroposterior diameter of the pelvis decreased from 30 to 8 mm. The resistive index of the blood flow in the renal vessels decreased from 0.74 to 0.58. The Hellström – Chapman robotic procedure is a safe and effective procedure for the correction of vasorenal hydronephrosis. However, this surgery requires patient selection to ensure future treatment success.