Efferent Vessels Research Articles

Multi-physics approach to model the lymph transport in the murine immune system

Abstract We formulate a compartmental model of the murine lymphatic system with the transfer rate parameters derived from the data on the geometric characteristics of the lymphatic system (LS) graph structure and the Hagen–Poiseuille-based values of the lymph flows through the system components, i.e., vertices and edges. It is supplemented by the physics-based model of lymph node draining-related function which considers a paradigmatic view of its geometry with one- and three-afferent lymphatic vessels and one efferent vessel, and the lymph flow described by the Darcy–Starling equations. We discuss further modelling work needed to gain a predictive understanding of the LS function in response to various perturbations including infections and therapeutic treatments.

6413 Anti-PD1 induces T1D in an HLA-DQ8, HLA-A2.1 mouse model

Abstract Disclosure: P. Houeiss: None. S. luce: None. C. Boitard: None. Anti-PD1 is an immune checkpoint inhibitor that has revolutionized cancer treatment. It blocks the interaction between PD1, a receptor on the surface of activated or exhausted T cells, and its ligands PDL1 and PDL2, to inhibit the immune response. However, anti-PD1 induces T1D in 0.4-2% of patients raising questions about the risk factors and the mechanisms behind T1D development. Since the pancreas of these patients is inaccessible, we focus on autoimmune diabetes induction in a transgenic mouse model modified to express the T1D susceptibility genes HLA-DQ8, HLA-A2.1 and the human preproinsulin and on identifying new targets to prevent or treat this disease. Thus, 8 to 12 weeks old mice were treated initially with 500 micrograms of anti-PD1 followed by 250 micrograms every other day for 10 days. Control mice received 6 injections of PBS. Mice were followed up for evidence of hyperglycemia for 60 days. Cells and tissues from the pancreas, and the spleens were isolated 15-, 30- or 60-days post-treatment initiation and analyzed by flow cytometry and immunohistochemistry. Although diabetes incidence in treated mice was 14% (n=14), insulitis incidence progressively increased over time reaching 86% on D60 (p=0.005). On Day 15, in the spleen, a significant 10% increase of CD4+Foxp3+CD25- T cells at the expense of the CD4+Foxp3- T cells were seen in the treatment group as compared to the control (37.1±4.25 vs 26±3.5, p<0.01, n=5 per group). In the treatment group, PD1 expression significantly increased on CD4+Foxp3+ T cells whereas PDL1 expression increased on CD4+Foxp3- and CD8+ T cells (p<0.01). On D30, in the pancreas, infiltrates show positive staining for F4/80+, CD4+ and CD8+ T cells with scarce foxp3+ T cells. While the absolute percentage of CD4+Foxp3+ T cells increased in the insulitis and diabetes group, their percentage among CD3+ T cells decreased in the insulitis (10.2%) and diabetes group (3.9%) as compared to the control group (13.5%). Infiltrates were concentrated around the islets and the efferent and afferent vessels, and extended to the exocrine pancreas, leading to secondary acinar destruction. In the pancreatic infiltrates from anti-PD1 treated mice, we noted a significant increase in CD4+ T cells recognizing Ins13-21 monomers as compared to the negative control. PD1 blockade induced an insulitis characterized by a Treg to effector T cells imbalance. Thus, it acted on the early phase of T1D. In conclusion, this model describes a new T1D endotype that shares similarities with ICI induced diabetes in patients. Presentation: 6/2/2024

9300 Anti-PD1 induces T1D in an HLA-DQ8, HLA-A2.1 mouse model

Abstract Disclosure: P. Houeiss: None. S. luce: None. C. Boitard: None. Anti-PD1 is an immune checkpoint inhibitor that has revolutionized cancer treatment. It blocks the interaction between PD1, a receptor on the surface of activated or exhausted T cells, and its ligands PDL1 and PDL2, to inhibit the immune response. However, anti-PD1 induces T1D in 0.4-2% of patients raising questions about the risk factors and the mechanisms behind T1D development. Since the pancreas of these patients is inaccessible, we focus on autoimmune diabetes induction in a transgenic mouse model modified to express the T1D susceptibility genes HLA-DQ8, HLA-A2.1 and the human preproinsulin and on identifying new targets to prevent or treat this disease. Thus, 8 to 12 weeks old mice were treated initially with 500 micrograms of anti-PD1 followed by 250 micrograms every other day for 10 days. Control mice received 6 injections of PBS. Mice were followed up for evidence of hyperglycemia for 60 days. Cells and tissues from the pancreas, and the spleens were isolated 15-, 30- or 60-days post-treatment initiation and analyzed by flow cytometry and immunohistochemistry. Although diabetes incidence in treated mice was 14% (n=14), insulitis incidence progressively increased over time reaching 86% on D60 (p=0.005). On Day 15, in the spleen, a significant 10% increase of CD4+Foxp3+CD25- T cells at the expense of the CD4+Foxp3- T cells were seen in the treatment group as compared to the control (37.1±4.25 vs 26±3.5, p<0.01, n=5 per group). In the treatment group, PD1 expression significantly increased on CD4+Foxp3+ T cells whereas PDL1 expression increased on CD4+Foxp3- and CD8+ T cells (p<0.01). On D30, in the pancreas, infiltrates show positive staining for F4/80+, CD4+ and CD8+ T cells with scarce foxp3+ T cells. While the absolute percentage of CD4+Foxp3+ T cells increased in the insulitis and diabetes group, their percentage among CD3+ T cells decreased in the insulitis (10.2%) and diabetes group (3.9%) as compared to the control group (13.5%). Infiltrates were concentrated around the islets and the efferent and afferent vessels, and extended to the exocrine pancreas, leading to secondary acinar destruction. In the pancreatic infiltrates from anti-PD1 treated mice, we noted a significant increase in CD4+ T cells recognizing Ins13-21 monomers as compared to the negative control. PD1 blockade induced an insulitis characterized by a Treg to effector T cells imbalance. Thus, it acted on the early phase of T1D. In conclusion, this model describes a new T1D endotype that shares similarities with ICI induced diabetes in patients. Presentation: 6/2/2024

Not All Patients with a Headache need a CT Scan, but they should be Listened to, and also with a Stethoscope: A Report of a Large Arteriovenous Malformation with a Loud Cranial Bruit.

Arteriovenous malformations (AVMs) are abnormal direct connections between arterial and venous systems, without an interposed capillary bed. This permits high-flow arteriovenous shunting, which precipitates structural changes in the afferent and efferent vessels, namely arterial smooth muscle hyperplasia and thinning of venous walls. Patients with intracranial AVMs typically present with a haemorrhage, headache or seizure. Treatment is either via medical management aimed at control of seizures, headache and blood pressure, or interventional via surgical, radiation or radiologically guided embolisation. We report the case of a woman in her early 40s presenting with a tonic-clonic seizure against a background of a 31-year history of migraine and an 18-month history of tremors in her right arm. The clinical examination was remarkable for an extremely loud cranial bruit and a right homonymous hemianopia. Imaging diagnosed an 8 cm Martin-Spetzler grade V intracranial arteriovenous malformation in her left parietal lobe, which was deemed unsuitable for operative or radiotherapy-based intervention. The patient was managed through observation and relatively good control of her breakthrough seizures was achieved through the addition of brivaracetam to her lamotrigine and carbamazepine-based therapy, six years after her initial presentation. Arteriovenous malformations may go undetected for decades.The presence of a cranial bruit is an important sign and tool in diagnosing an intracranial arteriovenous malformation. The presence of a homonymous hemianopia, of which a patient may be unaware, helps to localise an intracranial lesion.The risks of operative or radiological intervention must be balanced with the risks of haemorrhage or refractory seizure when adopting a strategy for the treatment of an intracranial arteriovenous malformation. Good control of epileptic symptoms in those deemed not suitable for operative or radiological intervention can be achieved by careful titration of anti-seizure medications.

Lymphatic spread from left-sided intrahepatic cholangiocarcinoma: reconsiderations based on the lymphatic drainage from the liver

Intrahepatic cholangiocarcinoma (ICC) is known to have a high frequency of lymph node metastasis. Lymph node dissection (LND) is recommended for accurate staging, but the survival benefit of LND remains unclear. Knowledge of the pathways and direction of lymphatic drainage to the regional lymph nodes is essential when considering LND to improve patient survival. The liver has three lymphatic drainage pathways: portal, sublobular, and subcapsular. Of these, the portal lymphatic pathway, which lies along with the portal tracts, is the primary pathway. The efferent portal lymphatic vessels from the left-sided liver, which continue from the portal lymphatic pathway of the liver, communicate with the lymphatic vessels and lymph nodes along the hepatic artery at the hepatoduodenal ligament. In addition, lymphatic flow may also present along the left embryonic (aberrant) hepatic artery in the lesser omentum, based on our experience. This pathway is the previously reported pathway from the left-sided ICC to the lesser curvature of the stomach. However, through this pathway, ICC cells reach lymph nodes along the root of the left gastric artery but not the perigastric lymph nodes along the lesser curvature because of the opposite direction of lymph flow. Although further analyses using a large number of cases are needed to confirm these observations, these two pathways, along the hepatic artery at the hepatoduodenal ligament and the left embryonic (aberrant) hepatic artery in the lesser omentum should be considered when performing LND in the case of ICC in the left-sided liver.

A Twisted Tale of Vein of Galen Aneurysmal Malformation

AbstractThis illustration presents a three-dimensional representation of the vascular structure of the vein of Galen aneurysmal malformation (VGAM), which is a rare congenital brain vascular abnormality characterized by the enlargement of the embryonic precursor of the vein of Galen—specifically, the median prosencephalic vein of Markowski. VGAM constitutes an arteriovenous fistula formed between the deep choroidal arteries and the embryonic median prosencephalic vein. Its development initiates early but is typically detectable via sonography only during the second- or third-trimester of gestation. The comprehensive assessment of the vascular anatomy of VGAM necessitates the examination of both the incoming (afferent) and outgoing (efferent) vessels.

Supermicrosurgery lymphaticovenous and lymphaticolymphatic anastomosis: Technical detail and short-term follow-up for immediate lymphatic reconstruction in breast cancer treatment-related lymphedema prevention

ObjectiveWe describe the feasibility and short-term outcome of our surgical technique to repair the lymph vessel disruption directly after axillary lymph node dissection during breast cancer surgery. This procedure is called immediate lymphatic reconstruction to prevent breast cancer treatment-related lymphedema (BCRL), which frequently occurs after axillary lymph node dissection. The surgical technique consisted of lymphaticovenous anastomosis (LVA) or lymphaticolymphatic anastomosis. We named the procedure lymphatic bypass supermicrosurgery (LBS). MethodsThis study used a retrospective cohort design of patients with breast cancer between May 2020 and February 2023. LBS was performed by making an intima-to-intima coaptation between afferent lymph vessels and the recipient's veins (LVA) or efferent lymph vessels lymphaticolymphatic anastomosis. ResultsA total of 82 patients underwent lymphatic bypass. The mean age of patients was 50 ± 12 years, and most had stage III breast cancer (n = 59 [72%]). LVA was the most common type of lymphatic bypass (94.6%). The median number of LVA was 1 (range, 1-4) and 1 (range, 1-3) for lymphaticolymphatic anastomosis. The median follow-up time was 12.5 months (range, 1-33 months). The 50 patients who had postoperative indocyanine green lymphography described arm dermal backflow stage 0 in 20 (40%), stage 1 in 19 (38%), stage 2 in 2 (4%), and stage 3 in 9 (18%) cases. The proportion of BCRL was 11 (22%), and subclinical lymphedema was 19 (38%) in this period. Most cases were in stable subclinical lymphedema (10, 58.8%). The 1-year and 2-year BCRL rates were 14% (95% confidence interval, 4%-23.9%) and 22% (95% confidence interval, 10.1%-33.9%), respectively. ConclusionsAlong with the emerging immediate lymphatic reconstruction, LBS is a feasible supermicrosurgery technique that may have a potential role in BCRL prevention. A randomized controlled study would confirm the effectiveness of the technique.

Endovascular aortic repair with sac embolization for the prevention of type II endoleaks (the EVAR-SE study): study protocol for a randomized controlled multicentre study in Germany

BackgroundBeyond a certain threshold diameter, abdominal aortic aneurysms (AAA) are to be treated by open surgical or endovascular aortic aneurysm repair (EVAR). In a quarter of patients who undergo EVAR, inversion of blood flow in the inferior mesenteric artery or lumbar arteries may lead to type II endoleak (T2EL), which is associated with complications (e.g. AAA growth, secondary type I endoleak, rupture). As secondary interventions to treat T2EL often fail and may be highly invasive, prevention of T2EL is desirable. The present study aims to assess the efficacy of sac embolization (SE) with metal coils during EVAR to prevent T2EL in patients at high risk.MethodsOver a 24-month recruitment period, a total of 100 patients undergoing EVAR in four vascular centres (i.e. Klinikum rechts der Isar of the Technical University of Munich, University Hospital Augsburg, University Hospital Dresden, St. Joseph’s Hospital Wiesbaden) are to be included in the present study. Patients at high risk for T2EL (i.e. ≥ 5 efferent vessels covered by endograft or aneurysmal thrombus volume <40%) are randomized to one group receiving standard EVAR and another group receiving EVAR with SE. Follow-up assessments postoperatively, after 30 days, and 6 months involve contrast-enhanced ultrasound scans (CEUS) and after 12 months an additional computed tomography angiography (CTA) scan. The presence of T2EL detected by CEUS or CTA after 12 months is the primary endpoint. Secondary endpoints comprise quality of life (quantified by the SF-36 questionnaire), reintervention rate, occurrence of type I/III endoleak, aortic rupture, death, alteration of aneurysm volume, or diameter. Standardized evaluation of CTA scans happens through a core lab. The study will be terminated after the final follow-up visit of the ultimate patient.DiscussionAlthough preexisting studies repeatedly indicated a beneficial effect of SE on T2EL rates after EVAR, patient relevant outcomes have not been assessed until now. The present study is the first randomized controlled multicentre study to assess the impact of SE on quality of life. Further unique features include employment of easily assessable high-risk criteria, a contemporary follow-up protocol, and approval to use any commercially available coil material. Overcoming limitations of previous studies might help SE to be implemented in daily practice and to enhance patient safety.Trial registration ClinicalTrials.gov NCT05665101. Registered on 23 December 2022.

Vascularized lymph node transfer with efferent lymphatico-lymphatic anastomosis for treatment of upper extremity lymphedema

Vascularized lymph node transfers (VLNT) are useful options for the surgical treatment of lymphedema. Conventional VLNT does not include the reconstruction of physiological lymphatic outflow, which may pose a risk of postoperative lymphatic vessel obstruction and lymph node sclerosis. We report a case of lymph flow bypass reconstruction using a superficial circumflex Iliac artery perforator (SCIP) flap, including VLNT with efferent lymphatico-lymphatic anastomosis. A 63-year-old female with severe right upper extremity lymphedema after mastectomy was reconstructed using a SCIP free flap, which included a vascularized lymph node elevated from the left groin area and transferred to the right axilla area. The SCIP vessels were anastomosed to the medial intercostal artery perforator vessels and the efferent lymphatic vessel from the vascularized lymph node was anastomosed to the internal mammary lymphatic vessels using supermicrosurgical technique. Indocyanine green lymphography showed the reconstructed lymphatic flow from the right hand to the right internal mammary lymphatics through the transferred flap. Postoperatively, lymphedema improved and there was no lymphedema at the donor site with a 2-year follow-up. Lymphatic flow bypass reconstruction using VLNT with efferent lymphatico-lymphatic anastomosis may provide a useful option for the treatment of severe lymphedema.

Changes of biliary cilia, smooth muscle tissue distribution, innervation and extracellular matrices during morphological evolution of hepatic architectures in vertebrates

BackgroundThe liver architecture of vertebrates can be classified into two types, the portal triad type (having periportal bile ducts) and the non-portal triad type (having bile ducts independent of the course of portal veins). The former is typically detectable in livers of tetrapods and cartilaginous fish, and its ancestral state is found in the hagfish, an earliest diverged lineage among vertebrates. Teleosts other than osteoglossomorphs have the latter. The aim of the present study is to reveal the changes of the hepatic innervation, biliary cilia and smooth muscle distribution, and extracellular matrices along vertebrate evolution with attention to the two types of liver architectures. MethodsThe hepatic innervation, biliary cilia and smooth muscle distribution, and collagen deposition were immunohistochemically and histochemically compared among livers of various vertebrates, using anti-acetylated tubulin and anti-α-smooth muscle actin antibodies, and Sirius red staining. These were also ultrastructurally examined. ResultsAlthough the hagfish liver had periportal intrahepatic bile ducts and ductules as detected in mammalian livers, it lacked smooth muscles around bile ducts and portal veins. Extracellular matrices in their connective tissues had thick collagen fibers. Its innervation was restricted to intrahepatic bile ducts and portal veins in the hilum. In livers of other vertebrates, including teleosts, the innervation was broadly detectable, especially around bile ducts, hepatic arteries and portal veins (afferent vessels), but not around central veins (efferent vessels). The chondrichthyans ultrastructurally had smooth muscle tissue around bile ducts. Cilia distribution was confirmed in intrahepatic bile ducts of tetrapods and basal actinopterygians. Teleosts other than osteoglossomorphs lacked cilia in their intrahepatic bile ducts. ConclusionsThe liver architecture of the hagfish may be unique for innervation and extracellular matrices. Hepatic innervation may not have occurred in vertebrate ancestors. Hepatic innervation in bile ducts, hepatic arteries and portal veins may have been conserved among the extant jawed vertebrates. Cilia distribution in bile ducts may have changed during evolution of actinopterygians.

Efferent blood supply to the right hepatic lobe regarding its transplantation from a living donor: reconstruction features. Part 2

Aim . To present the technical features and results of transplantation of the right hepatic lobe from a living donor with various types of efferent venous anatomy. Materials and methods. 306 liver transplantations from living related donors were performed from 2009 to 2021. Patients with previously described 14 subtypes of efferent vascular anatomy and classified into 3 types, were divided into 4 groups depending on the number of reconstructed vessels. The author analyzed anatomy variants of the right hepatic lobe, duration of surgery and anhepatic period, postoperative morbidity, volume of blood loss, including with allowance for the number of reconstructed vessels, as well as survivability. Results . The study demonstrated the principles and features of the reconstruction of the efferent veins of the graft. Time of surgical intervention, duration of anhepatic period, and postoperative morbidity were greatest with a separate type of blood outflow ( p &lt; 0.05) Blood loss was greatest during reconstruction veins 3 and 4 ( p &lt; 0.05). No difference in blood loss was detected between groups 3 and 4. Survivability within 12, 36, 60 and 120 months accounted for 84%, 83%, 81% and 71%, correspondingly, without any difference between groups. Conclusion . Successful transplantation of the right hepatic lobe requires precision mapping of the venous anatomy of the donor, preserving all potentially important efferent vessels, and commitment to the most complete reconstruction of them, irrespective of the vascular anatomy complexity.

Efferent blood supply to the right hepatic lobe regarding its transplantation from a living donor: variant anatomy, classification. Part 1

Aim. To describe new data and to complement the existing information about the anatomic features of the hepatic vein structure in the donor of the right hepatic lobe, to formulate the principles of donor selection proceeding from vascular anatomy.Materials and methods. 306 liver transplantations from living related donors were performed at A.I. Burnazyan Federal Medical Biophysical Center of Federal Medical and Biological Agency of Russia from 2009 to 2021. The vascular anatomy of 518 potential donors was analyzed. The prevalence of different vein structures of the right hepatic lobe was assessed.Results. The authors identified 14 subtypes of anatomy of efferent vessels. They were classified into 3 types depending on the contribution of the median vein to the blood outflow from the right hepatic lobe: caval (67.3%), cava medial (semi-separate, 29%), and separate (3.6%).Conclusion. The anatomy of the efferent vessels of the right lobe graft is characterized by variability and complexity. It requires accurate assessment at the preoperative stage (CT scanning) to be ready for reconstruction of any complexity.

The Effectiveness of Fluoroscopy-Guided Manual Lymph Drainage as Part of Decongestive Lymphatic Therapy on the Superficial Lymphatic Architecture in Patients with Breast Cancer-Related Lymphoedema: A Randomised Controlled Trial

The objective of this trial was to investigate the effectiveness of fluoroscopy-guided manual lymph drainage (MLD), as part of decongestive lymphatic therapy (DLT), on the superficial lymphatic architecture in patients with chronic mild to moderate breast cancer-related lymphoedema (BCRL). This trial was a multicentre, double-blind, randomised controlled trial involving 194 participants with BCRL. Participants were randomised into (1) DLT with fluoroscopy-guided MLD (intervention group), (2) DLT with traditional MLD (control group), or (3) DLT with placebo MLD (placebo group). Superficial lymphatic architecture was evaluated as a secondary outcome, visualised by ICG lymphofluoroscopy at the baseline (B0), post-intensive (P), and post-maintenance phases (P6). Variables were (1) number of efferent superficial lymphatic vessels leaving the dermal backflow region, (2) total dermal backflow score, and (3) number of superficial lymph nodes. The traditional MLD group showed a significant decrease in the number of efferent superficial lymphatic vessels at P (p = 0.026), and of the total dermal backflow score at P6 (p = 0.042). The fluoroscopy-guided MLD and placebo group showed significant decreases in the total dermal backflow score at P (p < 0.001 and p = 0.044, respectively) and at P6 (p < 0.001 and p = 0.007, respectively); the placebo MLD group showed a significant decrease in the total number of lymph nodes at P (p = 0.008). However, there were no significant between-group differences for the changes in these variables. In conclusion, based on lymphatic architecture outcomes, the added value of MLD, in addition to the other parts of DLT, could not be demonstrated in patients with chronic mild to moderate BCRL.

Isolation of lymph shows dysregulation of STAT3 and CREB pathways in the spleen and liver during leukemia development in a rat model.

Acute myeloid leukemia (AML) is a heterogeneous malignant condition characterized by massive infiltration of poorly differentiated white blood cells in the blood stream, bone marrow, and extramedullary sites. During leukemic development, hepatosplenomegaly is expected to occur because large blood volumes are continuously filtered through these organs. We asked whether infiltration of leukemic blasts initiated a response that could be detected in the interstitial fluid phase of the spleen and liver. We used a rat model known to mimic human AML in growth characteristics and behavior. By cannulating efferent lymphatic vessels from the spleen and liver, we were able to monitor the response of the microenvironment during AML development. Flow cytometric analysis of lymphocytes showed increased STAT3 and CREB signaling in spleen and depressed signaling in liver, and proteins related to these pathways were identified with a different profile in lymph and plasma in AML compared with control. Additionally, several proteins were differently regulated in the microenvironment of spleen and liver in AML when compared with control. Interstitial fluid, and its surrogate efferent lymph, can be used to provide unique information about responses in AML-infiltered organs and substances released to the general circulation during leukemia development.

Hamartomas of the Retina and Optic Disc.

Hamartomas are local malformation of cells that demonstrate abnormal proliferation in the area where they are normally present. Retinal and optic disc hamartomas include astrocytic hamartoma, congenital hypertrophy of the retinal pigment epithelium (CHRPE), simple congenital hamartoma of the retinal pigment epithelium (CSHRPE), combined hamartoma of the retina and retinal pigment epithelium (CHRRPE), retinal hemangioblastoma (retinal capillary hemangioma), and retinal cavernous hemangioma. Retinal and optic disc hamartomas can be observed sporadically as well as with systemic associations. Astrocytic hamartoma usually appears as a flat, transparent yellowish lesion. CHRPE is a round, pigmented, and flat lesion. CSHRPE usually presents as a dark black macular tumor. CHRRPE consists of vascular, glial, and pigment epithelial components, which can demonstrate peripapillary, macular, and peripheral localization. Retinal hemangioblastoma is a vascular tumor, red-pink in color with tortuous and dilated afferent and efferent vessels, typically located in the peripheral retina or optic disc. Retinal cavernous hemangioma is characterized by the formation of thin-walled saccular angiomatous structures in the retina or optic nerve head resembling concord grapes. Ultrasonography, fundus autofluorescence, optical coherence tomography, optical coherence tomography angiography, and fluorescein angiography methods are used in the diagnosis of retinal and optic disc hamartomas. Some retinal and optic disc hamartomas do not require treatment. However, complications including vitreous hemorrhage, macular exudation, retinal detachment, macular hole, epiretinal membrane, and choroidal neovascularization require treatment.

Nanoadjuvants Actively targeting lymph node conduits and blocking tumor invasion in lymphatic vessels.

Great efforts have been made to manipulate nanoparticles (NPs) with a diameter of 10-100nm to passively target lymph nodes (LNs) to magnitude anti-tumor activity of T cells. However, no attention has been paid to increasing the retention of NPs with active affinity in order to induce a prolonged release of antigens or molecular adjuvants in the LNs mattering the immune response. Here, we formulated two NPs encapsulated with imiquimod (IMQ), a TLR7/8 agonist, and paclitaxel (PTX) and further modified them with tannic acid (TA), respectively, to generate IMQ NP and PTX NP with a final diameter of approximately 40nm. Attributing a strong affinity of TA molecules to the elastin of LN conduits, the TA modified IMQ NPs can bypass the gaps in the layer of lymphatic endothelial cells and enter the paracortex through the lymph node capsule-associated (LNC) conduits. Similarly, the TA modified PTX NPs increased delivery of PTX to the metastatic tumor site in LNs, where the tumor-associated antigens were released and presented by conduits-lining dendritic cells to activate T cells. Thus, the NPs with deposition to LN conduits showed excellent performance in preventing lymphovascular invasion of triple-negative breast cancer cells and lung metastasis thereafter. On the contrary, the NPs without TA flowed through the subcutaneous sinus existing LNs directly by efferent lymphatic vessels showing relatively poor therapeutic outcomes. This study reveals that TA may mediate the long retention of antigens and molecular adjuvants to be delivered to deep LNs for developing potent vaccination technology.

Robotic-Assisted Resection of Pelvic Arteriovenous Malformation Utilising Intraoperative Video Angiography with Indocyanine Green

<h3>Study Objective</h3> Surgical resection of pelvic arteriovenous malformations (AVM) can be challenging, and pre-operative imaging may not clearly identify feeding vessels. We describe a case of pelvic AVM in a young woman and demonstrate the robotic surgical resection utilising video angiography with indocyanine green (ICG). <h3>Design</h3> Case report and surgical video. <h3>Setting</h3> Four-arm robotic assisted laparoscopy. <h3>Patients or Participants</h3> A nullipara with pelvic AVM. <h3>Interventions</h3> Robotic-assisted resection of pelvic AVM guided by intraoperative ICG angiography. <h3>Measurements and Main Results</h3> A 22-year-old woman presented with progressively worsening left pelvic pain. Pelvic ultrasound demonstrated a 7cm left adnexal vascular mass and magnetic resonance angiogram confirmed a left pelvic AVM. The patient was counselled regarding the risks of embolization versus surgery and decided on the latter. Using a robotic surgical system, the left pelvic side wall was opened at the pelvic brim and careful dissection of the retroperitoneal alveolar tissue was performed. 3mL of a 2.5mg/mL solution of ICG was injected peripherally, followed by 10mL bolus of normal saline. Using the near infra-red imaging of the robotic system, the ICG demonstrates small efferent vessels arising from the left ovarian vessels and a large vein communicating with the left external iliac vein. Vascular clips were applied to the aberrant vein prior to ligation. The AVM was carefully dissected away from the surrounding tissues, with use of bipolar diathermy for coagulation of smaller vessels. A further dose of ICG was injected after resection to ensure haemostasis and to confirm the perfusion of remaining organs. Mesosalpinx and pelvic side wall peritoneum were closed with 2-0 barbed suture. The patient was discharged the following day with complete resolution of left pelvic pain and normal pelvic ultrasound scan 6 weeks later. <h3>Conclusion</h3> Robotic surgical resection of pelvic AVM is enhanced with guidance from intraoperative ICG video angiography to ensure haemostasis and complete excision.

Micro-macroscopic anatomy of the lymphatic vessels and lymph nodes that form the parietal lymphatic pathways of the human thoracic cavity

Introduction: Many pathological processes such as infections, intoxications, and malignant tumors were spread through the lymphatic vessels of the thoracic cavity. In the present study, we investigated the anatomy of the lymphatic vessels and lymph nodes of the thoracic cavity in humans.&#x0D; Materials and methods: The examination was performed on 60 cadavers of fetuses (25), newborn children (14), children (11), and adults (10). Lymphatic vessels of the rib periosteum, costovertebral, costotransverse, and sternocostal joints, as well as parietal lymphatic vessels and lymph nodes of the thoracic cavity were studied. A comparative study of arterial, venous, and lymphatic vessels was carried out.&#x0D; Results: The parietal lymph nodes of the thoracic cavity include parasternal (localized along the course of the thoracic arteries and veins), paramammary (located near the lateral edge of the pectoralis major muscle), intercostal, paravertebral, and upper diaphragm. The efferent lymphatic vessels of the periosteum and perichondrium of the first three ribs go to the intercostal lymph nodes, to the parasternal, paravertebral and diaphragmatic lymph nodes.&#x0D; Conclusion: The presence of intercalated lymph nodes on the thoracic cavity is characteristic of the entire lymphatic system and should be considered in the pathology of the thoracic cavity.

Thoracic Duct Lymphangiography via the Testicular Parenchyma in a Rabbit Model

This study aimed to establish an animal model for thoracic duct lymphangiography using ethiodized oil. Thoracic duct lymphangiography was performed via the testes in 21 Japanese white rabbits. The testicular parenchyma was punctured by palpation using a 30-gauge, 0.5-inch needle. Ethiodized oil was injected at a rate of 11.41 mL/h until the testicular efferent lymphatic vessels were delineated and then at a rate of 2.85 mL/h until the entire thoracic duct was delineated. Thoracic duct delineation was 100% successful and showed good depiction based on visual scores. The mean ethiodized oil dose administered was 4.59 mL ± 1.41, and the mean time to visualize the entire thoracic duct was 43.7 minutes ± 14.1. The presented model may serve as a method for future preclinical investigation of the thoracic duct anatomy and for thoracic duct interventions.

Added Value of Selective Intra-arterial Cone-Beam CT Angiography in the Management of Visceral Artery Aneurysms

Purpose: The aim of this study is to evaluate the value of selective intra-arterial cone-beam computed tomography angiography (CBCTA) relative to conventional computed tomography angiography (CTA) in understanding visceral artery aneurysm (VAA) morphology, and its impact on treatment planning. Materials and Methods: Between January 2017 and August 2021, all patients who had a diagnosis of VAA and underwent intraoperative CBCTA imaging were retrospectively reviewed. Impact on treatment decisions, optimal C-arm angulations derived from CBCTA, and additional radiation exposure were reported. Two blinded independent reviewers qualitatively reviewed CBCTA and conventional CTA images. A 5-point Likert scale (1=poor image quality, 5=excellent image quality) was used to assess the overall image quality of each modality. Number of vessels arising from the aneurysm sac was counted. Results: A total of 16 patients had a diagnosis of VAA during the study period, of whom 10 patients had intraoperative CBCTA and conventional CTA available for review. Out of 10 patients, 7 underwent successful endovascular treatment, 2 were deemed not amenable for endovascular embolization based on intraoperative CBCTA findings, and 1 had resolved pseudoaneurysm. Total fluoroscopy time and radiation dose (dose area product [DAP] and skin dose) for all procedures were 27.7 ± 19.9 minutes, 28 362 (±18 651) µGy*m2, and 1879 (±1734) mGy, respectively. Radiation exposure from CBCTA (DAP and skin dose) was 5703 (±3967) µGy*m2 and 223.6 (±141.3) mGy, respectively. In patients who underwent endovascular treatment, the proportional DAP from CBCTA was 18.3% (±15.3%) of the total procedural radiation dose. Qualitative rating of overall image quality of CBCTA images was superior to CTA images (mean score: 4.55 vs 3, p<0.001). More branch vessels arising from the VAA were identified by all reviewers in CBCTA as compared with conventional CTA (median, min-max: 3, 0–4 vs 2,1–3 vessels). Conclusion: Intraoperative CBCTA after selective intra-arterial contrast injection, with better spatial resolution, provided better delineation of visceral aneurysm morphology as compared with conventional, intravenous CTA and enabled optimal treatment planning at a reasonable additional radiation exposure. Clinical Impact Visceral artery aneurysms (VAA) are often diagnosed incidentally by conventional computed tomographic angiography (CTA). Endovascular treatment typically requires selective angiographies at multiple projections to better understand aneurysm morphology, location, and efferent branch vessels. Intra-arterial cone-beam CT angiography (CBCTA) for VAA has the advantage of selective contrast opacification, better spatial resolution, and three-dimensional/multi-planar visualization of aneurysm morphology. In addition, CBCTA enables identification of optimal C-arm working projection for subsequent endovascular treatment. The aim of this study is to evaluate the value of intraoperative CBCTA relative to conventional CTA in understanding visceral artery aneurysm morphology and its impact on treatment planning.