Peritumoral Vessels Research Articles

Peritumoral Venous Vessels: Autobahn and Portal for T cells to Melanoma Brain Metastasis

Abstract Melanoma brain metastasis is associated with high morbidity and mortality and remains a major clinical challenge. Despite recent successes with combination immune checkpoint inhibitors (ICI) in the treatment of affected patients, the mechanistic underpinnings of T cell entry and response to these drugs in brain metastasis are poorly understood. Using real-time intravital microscopy, Messmer and colleagues identified peritumoral venous vessels (PVVs) as critical sites for T cell entry into brain metastases, a process accelerated by ICI treatment. The expression of intercellular adhesion molecule 1 (ICAM-1) on PVVs was found to be important for T cell recruitment in pre-clinical models and associated with increased T cell infiltration in human brain metastatic lesions. This study highlights PVVs as key vascular entry points for T cells into brain metastases, laying the foundation for enhancing the efficacy of cancer immunotherapies.

T lymphocyte recruitment to melanoma brain tumors depends on distinct venous vessels

To improve immunotherapy for brain tumors, it is important to determine the principal intracranial site of Tcell recruitment from the bloodstream and their intracranial route to brain tumors. Using intravital microscopy in mouse models of intracranial melanoma, we discovered that circulating Tcells preferably adhered and extravasated at a distinct type of venous blood vessel in the tumor vicinity, peritumoral venous vessels (PVVs). Other vascular structures were excluded as alternative Tcell routes to intracranial melanomas. Anti-PD-1/CTLA-4 immune checkpoint inhibitors increased intracranial Tcell motility, facilitating migration from PVVs to the tumor and subsequently inhibiting intracranial tumor growth. The endothelial adhesion molecule ICAM-1 was particularly expressed on PVVs, and, in samples of human brain metastases, ICAM-1 positivity of PVV-like vessels correlated with intratumoral Tcell infiltration. These findings uncover a distinct mechanism by which the immune system can access and control brain tumors and potentially influence other brain pathologies.

Ultrahigh-Resolution Visualization of Vascular Heterogeneity in Brain Tumors via Magnetic Nanoparticles-Enhanced Susceptibility-Weighted Imaging.

The precise assessment of vascular heterogeneity in brain tumors is vital for diagnosing, grading, predicting progression, and guiding treatment decisions. However, currently, there is a significant shortage of high-resolution imaging approaches. Herein, we propose a contrast-enhanced susceptibility-weighted imaging (CE-SWI) utilizing the minimalist dextran-modified Fe3O4 nanoparticles (Dextran@Fe3O4 NPs) for ultrahigh-resolution mapping of vasculature in brain tumors. The Dextran@Fe3O4 NPs are prepared via a facile coprecipitation method under room temperature, and exhibit small hydrodynamic size (28 nm), good solubility, excellent biocompatibility, and high transverse relaxivity (r2*, 159.7 mM-1 s-1) under 9.4 T magnetic field. The Dextran@Fe3O4 NPs-enhanced SWI can increase the contrast-to-noise ratio (CNR) of cerebral vessels to 2.5 times that before injection and achieves ultrahigh-spatial-resolution visualization of microvessels as small as 0.1 mm in diameter. This advanced imaging capability not only allows for the detailed mapping of both enlarged peritumoral drainage vessels and the intratumoral microvessels, but also facilitates the sensitive imaging detection of vascular permeability deterioration in a C6 cells-bearing rat glioblastoma model. Our proposed Dextran@Fe3O4 NPs-enhanced SWI provides a powerful imaging technique with great clinical translation potential for the precise theranostics of brain tumors.

Differential Diagnosis of Solid Pancreatic Lesions Using Detective Flow Imaging Endoscopic Ultrasonography.

The differential diagnosis of solid pancreatic lesions (SPLs) using B-mode endoscopic ultrasonography (EUS) is challenging. Detective flow imaging (DFI) offers the potential for detecting low-flow vessels in the pancreas, thus enhancing diagnostic accuracy. This retrospective study aimed to investigate DFI-EUS findings of SPLs and analyze their differential diagnostic accuracy for pancreatic cancer. We included 104 patients with pathologically confirmed SPLs who underwent EUS between April 2021 and June 2023. Expert endosonographers, blinded to the patients' clinical data, evaluated images obtained through B-mode, eFLOW, and DFI-EUS. The frame rate and vessel detection sensitivity were compared between eFLOW and DFI, and the diagnostic criteria for pancreatic cancer were established. The visualization rate for vessels in SPLs was significantly higher with DFI-EUS (96%) compared to eFLOW (27%). Additionally, DFI showed a superior frame rate, sensitivity (99%), and accuracy (88%) for detecting pancreatic cancer, although with a modest specificity (43%). On DFI-EUS, characteristics such as hypovascularity, peritumoral vessel distribution, or spotty vessel form were suggestive of pancreatic cancer. DFI-EUS significantly improved the visualization of vascular structures within the SPLs, highlighting its efficacy as a diagnostic modality for pancreatic cancer.

Measurement of Microvessel Density Using CD105 (Endoglin) as a Marker in Prostatic Adenocarcinoma

Introduction Angiogenesis has been proposed as a promising prognostic marker in a variety of tumours. Microvessel density (MVD) measurement is the most reliable method for the semiquantitative evaluation of angiogenesis. Endoglin (CD105) is a recognised marker of proliferating endothelium and is expressed in intra-tumoral as well as peri-tumoral vessels. It is upregulated in various cancers including prostate cancer, therefore, it is an upcoming prime marker for prognosis, tumour imaging and antiangiogenesis therapy. Aim The study was done to evaluate microvessel density (MVD) by using CD105 (endoglin) as an IHC marker in prostatic adenocarcinoma and to find its relationship with Gleason score and grade groups. Materials and methods This was an observational cross-sectional study under which a total of 31 histopathologically diagnosed cases of prostatic adenocarcinoma on TURP chips were included and were graded according to Gleason score and grades.IHC using endoglin (CD105) was done to detect the highest-density areas of stained vessels (hot spots). The highest value obtained in three hot spot fields was reported as microvessel density (MVD) and its relationship with Gleason score and grade groups was analysed. Results Most common age group was 71-80 years (48.39% cases). Maximum cases (45.16%) had a Gleason score of 9. The maximum mean MVD CD105 score was found in the Gleason grade group 5 (45.32%) while the minimum was in grade group 1 (24%). Comparison of mean MVD CD105 scores in different Gleason grade groups revealed a significant association of MVD CD105 with Gleason grade groups. Conclusion Endoglin measures microvessel density and its expression correlated with Gleason score and grade group. Hence it can be used as a potential prognostic marker in adenocarcinoma prostate.

90Y-/166Ho- ‘Radiation lobectomy’ for liver tumors induces abnormal morphology and impaired drainage of peritumor lymphatics

High-dose unilobar radioembolization, or 'radiation lobectomy' (RL), is an induction therapy that achieves contralateral future liver remnant hypertrophy while simultaneously irradiating the tumor. As such, it may prevent further growth, but it is unknown whether RL affects intrahepatic lymphatics, a major route via which liver tumors disseminate. This was a case-control study conducted at University Medical Center Utrecht. The study compared lymph vessels in livers that had undergone RL (cases) with those in livers that had not undergone RL (controls). Histological samples were acquired from patients diagnosed with hepatocellular carcinoma (HCC) or colorectal liver metastases (CRLM) between 2017 and 2022. Lymph vessel morphology was analyzed by two researchers using podoplanin, a protein that is expressed in lymphatic endothelium. Invivo liver lymph drainage of radioembolized livers was assessed using intraoperative liver lymphangiography (ILL): during liver surgery, patent blue dye was injected into the liver parenchyma, followed by inspection for staining of perihepatic lymph structures. ILL results were compared to a previously published cohort. Immunohistochemical analysis on post-RL tumor tissues from ten patients with CRLM and nine patients with HCC revealed aberrant morphology of irradiated liver lymphatics when compared to controls (n= 3 per group). Irradiated lymphatics were tortuous (p <0.05), thickened (p <0.05) and discontinuous (p <0.05). Moreover, post-RL lymphatics had larger lumens (1.5-1.7x, p <0.0001), indicating lymph stasis. ILL revealed diminished lymphatic drainage to perihepatic lymph nodes and vessels in irradiated livers when compared to non-radioembolized controls (p= 1.0x10-4). Radioembolization impairs peritumoral lymph vessel function. Further research is needed to evaluate if radioembolization impairs tumor dissemination via this route. Unilobar radioembolization can serve as an alternative to portal venous embolization for patients who are considered unresectable due to an insufficient future liver remnant. This research suggests that radioembolization impairs the function of peritumoral liver lymph vessels, potentially hindering dissemination via this route. These findings provide support for considering unilobar radioembolization over standard portal venous embolization.

Imaging Features of Alveolar Soft Part Sarcoma: Single Institution Experience and Literature Review.

Alveolar soft part sarcoma (ASPS) is an extremely rare and aggressive soft-tissue sarcoma (STS) subtype with poor prognosis and limited response to radiation therapy and chemotherapy. Prompt recognition and referral to sarcoma centers for appropriate management are crucial for patients' survival. The purpose of this study was to report ASPS pre-treatment imaging features and to examine the existing literature on this topic. Twelve patients (7 women, 5 men-mean age 27.1 ± 10.7 years) were included from our single-center experience. Ultrasonography (US), computed tomography (CT), and magnetic resonance imaging (MRI) available were reviewed according to an analysis grid incorporating features from the latest research on STS. Clinical, histological, and outcome data were collected. MRI was available in 10 patients (83.3%), US in 7 patients (58.3%), and CT in 3 patients (25%). Mean longest tumor diameter was 7.6 ± 2.9 cm, and all tumors were deeply seated. Large peritumoral feeding vessels were systematically found and identified on ultrasonography (7/7), MRI (10/10), and CT (3/3). US revealed a well-defined heterogeneous hypoechoic pattern, with abundant flow signals in all patients (7/7). In all patients, MRI showed mildly high signal intensity (SI) on T1-WI and high SI on T2-WI and peritumoral edema. Moreover, flow-voids (due to arteriosus high-flow) into the peritumoral/intratumoral feeding vessels were detected in the MRI fluid-sensitive sequences of all patients. At baseline, whole-body contrast-enhanced CT revealed metastases in 8/12 (66.7%) patients. A pre-treatment longest diameter > 5 cm was significantly associated with distant metastases at diagnosis (p = 0.01). A maximum diameter > 5 cm represents a risk of metastatic disease at diagnosis (odds ratio = 45.0000 (95% CI: 1.4908-1358.3585), p = 0.0285). In the comprehensive literature review, we found 14 articles (case series or original research) focusing on ASPS imaging, with a total of 151 patients included. Merging our experience with the data from the existing literature, we conclude that the hallmark of ASPS imaging at presentation are the following characteristics: deep location, a slight hyperintense MRI SI on T1-WI and a hyperintense SI on T2-WI, numerous MRI flow voids, high internal vascularization, and large peritumoral feeding vessels.

Pilot Study: FSHR Expression in Neuroendocrine Tumors of the Appendix.

Appendix neuroendocrine neoplasm (ANEN) treatment is based on tumor size and proliferation markers. Recently, the role of the follicle-stimulating hormone receptor (FSHR) from the clinical perspective has also been increasingly discussed. The FSHR is expressed in the endothelial cells of both intratumoral and peritumoral blood vessels, where it contributes to neoangiogenesis and blood vessel remodeling. FSHR expression is associated with a range of tumor types, such as gastrointestinal tumors, and it is not detected in healthy tissues located more than 10 mm from the tumor site or in tumor lymphatics. In this study, we evaluated the expression of FSHR and CD31 in the blood vessels of ANENs in females and males with confirmed histopathology. We conducted a quantitative analysis of the immunohistochemical reactions and found a higher number of microvessels in the mucosa and submucosa of neuroendocrine tumors in the appendix. A higher level of FSHR expression was observed in women. Future research should consider whether an elevated number of blood vessels along with a strong pattern of FSHR expression may influence future treatment strategies.

Abstract 1015: VEGFR-3 expression profiling by histology to classify patient population for the selective VEGFR-3 inhbitor EVT801

Abstract Introduction: EVT801 is a highly selective small molecule inhibitor of VEGFR-3 and acts by inhibiting tumor lymphangiogenesis and angiogenesis. Among the tyrosine kinase inhibitors, EVT801 has shown compelling activity in a wide range of cancer models and favorable preclinical toxicology profile. A phase I clinical study (NCT05114668) is underway to characterize safety, tolerability, pharmacokinetics of EVT801, and explore patient stratification which will be key for further development. Literature reports VEGFR-3 expression in several tumor cells - especially in kidney and liver cancers. However, we did not detect VEGFR-3 in tumor cells in translational in vivo models we explored (i.e., chemo-induced liver cancer and panel of PDX models). To clarify the situation, we validated a highly specific protocol for VEGFR-3 immunohistochemistry labelling, readily transferable to clinical centers. Results: We evaluated many different tumor types, and eventually focused our analysis on kidney cancer and soft tissue sarcomas. Initially, VEGFR-3 expression was assessed in 29 primary kidney cancer samples and 23 metastatic kidney cancer samples with CD34 to stain vessels and D2-40 to track lymphatics. We detected VEGFR-3 expression in the endothelial cells within the kidney tumor but not in the tumor cells. Remarkably, we observed a very distinct delineation between the kidney tumor vasculature, which showed high VEGFR-3 expression, and the normal adjacent tissue, which was devoid of VEGFR-3 expression. All vessels around and in the tumor were stained by CD34, whereas D2-40 staining was limited to the peritumoral regions. In addition, we found that VEGFR-3 expression in metastases from kidney tumors matched the expression pattern of the primary tumor. This held true even in patients treated with sunitinib, positioning EVT801 as a potential treatment option after failure of such multi tyrosine kinase inhibitors. Among the samples from 103 patients with soft tissue sarcomas, VEGFR-3 was generally highly expressed; however, 3 distinct groups emerged: i) tumors with high VEGFR-3 expression in tumor cells, tumor vessels and peritumoral vessels; ii) tumors with high expression in all vessels (tumor and peritumoral) but not in the tumor cells (similar to kidney tumors); iii) tumors with intermediate expression in peritumoral vessels. Conclusion: We were able to quantify VEGFR-3 expression in the kidney and soft tissue sarcoma cohorts plus several others, such as hepatocarcinoma and non-small cell lung cancer. This enables us selecting indications that might benefit from EVT801 as a monotherapy (e.g., clear cell renal cell carcinoma and soft tissue sarcomas) or in combination with standard of care. Accordingly, VEGFR-3 expression is retrospectively quantified during EVT801 clinical trial phase 1 trial and may be used to stratify patients in the future. Citation Format: michael Paillasse, pierre-benoit Ancey, Gaelle Badet, Anne Gomez-Brouchet, Janik Selves, philippe Rochaix, Maxime Battistella, Celeste Lebbe, philippe Cassier, carlos Gomez-Roca, Jean-Pierre Delord, Mark Whittaker, Lise Davenne, John Friend, Michael Fitzgerald, James Garner, Pierre Fons. VEGFR-3 expression profiling by histology to classify patient population for the selective VEGFR-3 inhbitor EVT801 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1015.

TGF-Beta Modulates the Integrity of the Blood Brain Barrier In Vitro, and Is Associated with Metabolic Alterations in Pericytes.

The blood-brain barrier (BBB) is a selectively permeable boundary that separates the circulating blood from the extracellular fluid of the brain and is an essential component for brain homeostasis. In glioblastoma (GBM), the BBB of peritumoral vessels is often disrupted. Pericytes, being important to maintaining BBB integrity, can be functionally modified by GBM cells which induce proliferation and cell motility via the TGF-β-mediated induction of central epithelial to mesenchymal transition (EMT) factors. We demonstrate that pericytes strengthen the integrity of the BBB in primary endothelial cell/pericyte co-cultures as an in vitro BBB model, using TEER measurement of the barrier integrity. In contrast, this effect was abrogated by TGF-β or conditioned medium from TGF-β secreting GBM cells, leading to the disruption of a so far intact and tight BBB. TGF-β notably changed the metabolic behavior of pericytes, by shutting down the TCA cycle, driving energy generation from oxidative phosphorylation towards glycolysis, and by modulating pathways that are necessary for the biosynthesis of molecules used for proliferation and cell division. Combined metabolomic and transcriptomic analyses further underscored that the observed functional and metabolic changes of TGF-β-treated pericytes are closely connected with their role as important supporting cells during angiogenic processes.

Synthetic phase-sensitive inversion-recovery vessel for assessing extramural venous invasion in patients with rectal cancer: imaging quality and added value to T2-wighted imaging.

To evaluate the imaging quality of a synthetic phase-sensitive inversion recovery (SyPSIR) vessel and to add value to T2-weighted imaging (T2WI) for extramural venous invasion (EMVI) detection in patients with rectal cancer. Participants in this retrospective study underwent preoperative synthetic MRI between October 2020 and April 2022. SyPSIR image reconstruction was performed with a single inversion time of 10 ms. A junior and a senior radiologist evaluated the imaging quality, including overall imaging quality scores, motion artifact scores, and relative image signal intensity contrast between the tumor and peritumoral vessels (SItumor-vessel), of both T2WI and SyPSIR vessels. Differences in imaging quality between the two methods were assessed using the Wilcoxon signed-rank test and two-sample t-test. EMVI scores were recorded for T2WI and T2WI+SyPSIR vessel. The area under the receiver operating characteristic curve (AUC) was calculated to evaluate the diagnostic performance. A total of 106 patients (35 EMVI+ and 71 EMVI-) were evaluated. There were no statistically significant differences in the overall image quality scores, motion artifacts, or SItumor-vessel (p = 0.08-0.93) between the T2WI and SyPSIR vessels. On combining T2WI and SyPSIR vessels, the AUC for pathological EMVI+ diagnoses increased from 0.65 to 0.88 for the junior radiologist and from 0.86 to 0.96 for the senior radiologist. Furthermore, the sensitivity of the analyses by junior and senior radiologists increased from 0.40 to 0.77 and 0.49 to 0.86, respectively. A SyPSIR vessel can provide additional information to improve the diagnostic efficiency of pathological EMVI in rectal cancer, which may be beneficial for individualized clinical treatment. • SyPSIR vessel and T2WI had similar imaging quality. • EMVI evaluation in SyPSIR vessel has a high inter-observer agreement. • The SyPSIR vessel has the potential to improve the diagnostic efficiency of EMVI detection in rectal cancer.

Abstract 2487: Distinct venous brain vessels provide structures for T lymphocyte recruitment to brain tumors in mouse models of intracranial melanoma

Abstract Immune checkpoint therapy has demonstrated potential for the treatment of brain metastases, but the mechanisms of lymphocyte recruitment to brain tumors are poorly understood. To monitor T cell infiltration and brain tumor growth in vivo in real time, we performed intravital microscopy of adoptively transferred and endogenous T cells in mouse models of intracranial melanoma. By spatio-temporal analysis of T cell infiltration dynamics in brain tumors we could identify a distinct type of venous blood vessels in the tumor vicinity, “peritumoral venous vessels” (PVVs). Intraluminal T cell attachment and T cell extravasation was increased at PVVs compared to intratumoral vessels. Moreover, PVVs were characterized by high perivascular T cell density, high T cell motility parameters and high expression of ICAM-1. PVVs were specifically exploited for the recruitment of T cells to melanoma brain tumors, whereas alternative T cell routes via brain structures such as brain capillaries, intratumoral blood vessels and parasagittal regions were not observed. Immune checkpoint inhibition increased T cell motility in the brain, facilitating the advance from PVV to tumor, which resulted in intracranial tumor growth inhibition. Our findings describe a distinct mechanism by which the immune system targets melanoma brain tumors, and, potentially, other intracranial pathologies. Citation Format: Julia M. Messmer, Manuel Piechutta, Varun Venkataramani, Chanté Mayer, Anna S. Berghoff, Daniel Hinze, Michael Hölzel, Iris Helfrich, Dirk Schadendorf, Wolfgang Wick, Matthia A. Karreman, Frank Winkler. Distinct venous brain vessels provide structures for T lymphocyte recruitment to brain tumors in mouse models of intracranial melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2487.

Using Peritumor and Intratumor Vascularity on Preoperative Imaging to Predict Fuhrman Grade Histology of Renal Tumors

Objective: To investigate if peritumor and/or intratumor vasculature is associated with high-grade tumor histology for renal cell carcinoma. Methods: A retrospective review at a tertiary care facility was performed of patients who underwent radical nephrectomy or partial nephrectomy for a renal tumor between January 2015 and December 2020. Data of tumor characteristics were collected from final pathology reports. A single radiologist specializing in genitourinary imaging reviewed all preoperative cross-sectional imaging for peritumor vessels and intratumor vessels. Single and multivariable logistic regression was utilized to identify variables associated with high-grade tumor histology. Results: The average tumor size on final pathology report was 6.4 cm (range 3.0-17.0 cm). Ninety-two patients (56.1%) had either an enlarged peritumor vessel (n = 72), an intratumor vessel (n = 3), or both a peritumor vessel and an intratumor vessel (n = 17). Of the 92 patients with either a peritumor vessel or both a peritumor vessel and intratumor vessel, 60.9% of these patients had high Fuhrman grade histology on final pathology report (60.9% vs 39.1%, p < 0.001). Pathologic stage T1a tumors with an enlarged peritumor vessel on preoperative imaging were associated with high Fuhrman grade histology (58.3% vs 41.7%, p = 0.015). Across all stages, the presence of an enlarged peritumor vessel was significantly associated with high Fuhrman grade (odds ratio: 2.37, 95% confidence interval 1.17-4.9, p = 0.01). Conclusion: Findings suggest that vessels surrounding small renal tumors and large renal tumors is associated with high tumor grade (Fuhrman grade >3). Further research is needed to support the association of peritumor vessels with high tumor grade.

Decreased cross-sectional muscle area in male patients with clear cell renal cell carcinoma and peritumoral collateral vessels.

BACKGROUNDSarcopenia is the loss of skeletal muscle mass (SMM) and is a sign of cancer cachexia. Patients with advanced renal cell carcinoma (RCC) may show cachexia.AIMTo evaluate the amount of SMM in male clear cell RCC (ccRCC) patients with and without collateral vessels.METHODSIn this study, we included a total of 124 male Caucasian patients divided into two groups: ccRCCa group without collateral vessels (n = 54) and ccRCCp group with collateral vessels (n = 70). Total abdominal muscle area (TAMA) was measured in both groups using a computed tomography imaging-based approach. TAMA measures were also corrected for age in order to rule out age-related effects.RESULTSThere was a statistically significant difference between the two groups in terms of TAMA (P < 0.05) driven by a reduction in patients with peritumoral collateral vessels. The result was confirmed by repeating the analysis with values corrected for age (P < 0.05), indicating no age effect on our findings.CONCLUSIONThis study showed a decreased TAMA in ccRCC patients with peritumoral collateral vessels. The presence of peritumoral collateral vessels adjacent to ccRCC might be a fine diagnostic clue to sarcopenia.

Suppression of Local Tumor Progression in Perivascular Hepatocellular Carcinoma by Combination Therapy with Radiofrequency Ablation and Percutaneous Ethanol Injection: A Propensity Score Matching Analysis

Background and Aims: Radiofrequency ablation (RFA) has replaced percutaneous ethanol injection (PEI) as the treatment of choice for hepatocellular carcinoma (HCC); however, control of local tumor progression (LTP) remains a challenge in perivascular HCC. The aim of this study was to determine whether PEI added to RFA can reduce the LTP rate in perivascular HCC patients. Methods: We retrospectively analyzed 167 patients, with 197 newly diagnosed HCC nodules with peritumoral vessels, who underwent either RFA plus PEI or RFA monotherapy as the first-line treatment between June 2001 and April 2015. Ethanol was injected inside the tumor close to the peritumoral vessels in the combination therapy group. Patients were matched 1:1 according to their propensity scores to reduce selection bias; cumulative LTP was then analyzed using log-rank tests and Cox proportional hazard regression analyses. Results: The two matched groups comprised 62 tumors each. The overall median follow-up period was 34 months (range, 1–140 months). In the RFA plus PEI group, the cumulative LTP rates were 5.7%, 15.5%, and 20.4% at 1, 3, and 5 years, respectively; in the RFA monotherapy group, the rates were 13.2%, 32.0%, and 40.2%, respectively. The rates were significantly lower in the RFA plus PEI group (p = 0.032). Cox proportional hazard regression analysis showed that PEI combination treatment was significantly associated with a reduced risk of local HCC recurrence (hazard ratio, 0.44; 95% confidence interval, 0.19–0.93; p = 0.031). Discussion/Conclusion: The risk of LTP after RFA for perivascular HCC can be significantly reduced by injecting ethanol close to the peritumoral vessels.

Immunohistochemical evaluation of CD31 and D2-40, expression in oral squamous cell carci-noma

Background: The present study was carried out to evaluate the relation between angiogenesis, and tumor stage of oral squamous cell carcinoma (OSCC).Materials and methods: Thirty formalin-fixed paraffin embedded blocks were used, ten of them were previously diagnosed as well differentiated OSCC, ten moderately differentiated OSCC and ten poorly differentiated OSCC. To determine the expression of CD31 and D2-40 proteins, streptavidin-biotin immunoperoxidase staining technique was used. The areas with the most vascular density (hot spots) were determined. The stained vessels were counted independently in intratumoral and peritumoral stroma. Results: CD 31 protein showed positive expression in the peritumoral and intratumoral blood vessels subjacent to the malignant invading nests. D2-40 expression was positive in lymphatic vessel in the peritumoral and intratumoral stroma subjacent to the invading nests. The highest mean values of both CD31 and D2-40 proteins expression were recorded in poor differentiated OSSC followed by moderate differentiated OSSC then well differentiated OSSC. There was statistically significant difference found between the three studied groups regarding CD31 and D2-40 levels. Also there was statistically significant positive correlation found between CD31 level and D2-40 level.Conclusion: CD31 and D2-40 are related to stage of OSCC and are consistent with angiogenesis in tumor progression.

Copper-Catalyzed Covalent Dimerization of Near-Infrared Fluorescent Cyanine Dyes: Synergistic Enhancement of Photoacoustic Signals for Molecular Imaging of Tumors.

Photoacoustic (PA) imaging relies on the absorption of light by chromophores to generate acoustic waves used to delineate tissue structures and physiology. Here, we demonstrate that Cu(II) efficiently catalyzes the dimerization of diverse near-infrared (NIR) cyanine molecules, including a peptide conjugate. NMR spectroscopy revealed a C-C covalent bond along the heptamethine chains, creating stable molecules under conditions such as a wide range of solvents and pH mediums. Dimerization achieved >90% fluorescence quenching, enhanced photostability, and increased PA signals by a factor of about 4 at equimolar concentrations compared to the monomers. In vivo study with a mouse cancer model revealed that dimerization enhanced tumor retention and PA signal, allowing cancer detection at doses where the monomers are less effective. While the dye dimers highlighted peritumoral blood vessels, the PA signal for dimeric tumor-targeting dye-peptide conjugate, LS301, was diffuse throughout the entire tumor mass. A combination of the ease of synthesis, diversity of molecules that are amenable to Cu(II)-catalyzed dimerization, and the high acoustic wave amplification by these stable dimeric small molecules ushers a new strategy to develop clinically translatable PA molecular amplifiers for the emerging field of molecular photoacoustic imaging.

Distinguishing Hepatocellular Carcinoma From Hepatic Inflammatory Pseudotumor Using a Nomogram Based on Contrast-Enhanced Ultrasound.

BackgroundHepatocellular carcinoma (HCC) and hepatic iflammatory pseudotumor (IPT) share similar symptoms and imaging features, which makes it challenging to distinguish from each other in clinical practice. This study aims to develop a predictive model based on contrast-enhanced ultrasound (CEUS) and clinical features to discriminate HCC from IPT.MethodsSixty-two IPT and 146 HCC patients were enrolled in this study, where pathological diagnosis served as the reference standard for diagnosis. Clinical and ultrasound imaging data including CEUS features: enhancement degree during arterial phase, portal phase and delayed phase, enhancement pattern, early washout within 60 s, feeding artery, peritumoral vessels, peritumoral enhancement, and margin of nonenhanced area were retrospectively collected. Imaging data were reviewed by two experienced ultrasound doctors. Patients were randomly assigned to training and validation sets. Chi-squared test followed by LASSO regression was performed on ultrasonographic features in the training set to identify the most valuable features that distinguish HCC from IPT, based on which the sonographic score formula was generated. With the significant clinical and ultrasonographic indicators, a nomogram was developed. The performance of the nomogram was verified by ROC curve and decision curve analysis (DCA) with the comparison with sonographic score and the ultrasound doctor’s diagnosis.ResultsThe most valuable ultrasonographic features that distinguish between HCC and IPT were enhancement degree during arterial phase, early washout, peritumoral vessels, peritumoral enhancement, and liver background. The sonographic score based on these features was verified to be an independent factor that predicts the diagnosis (p = 0.003). Among the clinical indicators, AFP (p = 0.009) and viral hepatitis infection (p = 0.004) were significant. Sonographic score, AFP, and viral hepatitis were used to construct a predictive nomogram. The AUC of the nomogram was 0.989 and 0.984 in training and validation sets, respectively, which were higher than those of sonographic score alone (0.938 and 0.958) or the ultrasound doctor’s diagnosis (0.794 and 0.832). DCA showed the nomogram provided the greatest clinical usefulness.ConclusionA predictive nomogram based on a sonographic signature improved the diagnostic performance in distinguishing HCC and IPT, which may help with individualized diagnosis and treatment in clinical practice.

The predictive value of MSCT imaging features on the pathological risk of gastrointestinal stromal tumors

Objective To investigate the predictive value of MSCT imaging features on the pathological risk of gastrointestinal stromal tumors (GISTs). Methods The MSCT manifestations of 120 GISTs patients confirmed by operation, pathology and immunohistochemistry were analyzed retrospectively. The age of tumor onset, location, maximum diameter, morphology, growth pattern, cystic necrosis, calcification, peritumoralfat space, enhancement pattern, peritumoralor intratumoral vessels, peak period of enhancement, metastasis, and the relationship between Ki-67 proliferation index and pathological risk grade were also analyzed. Results Among 120 cases, there were 55 cases of extremely low and low risk, 28 cases of moderate risk, and 37 cases of high risk. There were significant differences in location, tumor diameter, morphology, growth pattern, cystic necrosis, peritumoral fat space, enhancement pattern, peritumoral or intratumoral vessels, peak period of enhancement, and Ki-67 proliferation index of GISTs ( P < 0.05). There was no significant difference in calcification, CT plain scan, enhanced scan (3 phase), peak value and Ap、Vp、Dp of GISTs with different risk ( P > 0.05). Conclusion There are differences in the performance of multi-layer spiral CT (MSCT) in GISTs with different risk levels. It is closely related to the classification of pathological risk. For the diagnosis of GISTs, clinical treatment plan formulation and prognosis, it has important reference value. 摘要： 目的 探讨 MSCT 影像特征对胃肠道间质瘤 (GISTs) 病理危险度的预测价值。 方法 回顾性分析120例经手 术、病理及免疫组化证实的GISTs患者的MSCT表现, 分析肿瘤的发病年龄、部位、肿瘤最大径、形态、生长方式、囊变 坏死、有无钙化、瘤周脂肪间隙、强化方式、瘤周或瘤内血管、强化峰值所在期、有无转移以及Ki-67增殖指数与病理危 险程度分级之间关系。 结果 120例病例中分别有极低度和低度危险55例, 中度危险28例, 高度危险37例。不同危 险程度GISTs在病变的部位、肿瘤最大径、形态、生长方式、囊变坏死、瘤周脂肪间隙、强化方式、瘤周或瘤内血管以及 强化峰值所在期方面均有统计学差异( P < 0.05); Ki-67增殖指数方面有统计学差异 ( P < 0.05)。而不同危险度的 GISTs在病变有无钙化及CT平扫、增强扫描 (三期) CT值、强化峰值、Ap、Vp、Dp方面无统计学差异( P > 0.05)。 结论 不同危险度的GISTs的多层螺旋CT(MSCT)表现存在差异, 且与病理危险程度分级具有密切关系, 对GISTs 的诊断、临床治疗方案制订及判断预后有重要参考价值。

Subcutaneous Adipose Tissue Reduction in Patients with Clear Cell Renal Cell Carcinoma and Peritumoral Collateral Vessels: A Retrospective Observational Study

Background: peritumoral collateral vessels adjacent to renal cell carcinoma (RCC) can be encountered in clinical practice. Cancer cachexia is defined as a decrease of adipose and skeletal muscle tissues. In this study we evaluated, using a quantitative CT imaging-based approach, the distribution of abdominal adipose tissue in clear cell RCC (ccRCC) male patients with and without collateral vessels. Methods: between November 2019 and February 2020, in this retrospective study we enrolled 106 ccRCC male Caucasian patients divided into two groups: a ccRCCa group without collateral vessels (n = 48) and a ccRCCp group with collateral vessels (n = 58). The total adipose tissue (TAT), visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) areas were measured in both groups. Moreover, the VAT/SAT ratio was calculated for each subject. Results: a statistically significant difference between the two groups was found in the SAT area (p &lt; 0.05), while no significant differences were found in the TAT area, VAT area and VAT/SAT ratio. Conclusion: this study demonstrates a reduction of SAT in ccRCC patients with peritumoral collateral vessels.