Adjacent Vasculature Research Articles

Percutaneous microwave ablation of a transgenic large animal porcine liver tumor model after intra-arterial embolization

Objectives: Percutaneous ablation with microwave ablation (MWA) successfully treats hepatic tumors (HTs) up to 3 cm in size when appropriate margins are achieved. MWA is limited when treating larger HT due to the disbursement of heat from adjacent tissue and vasculature. Embolization before MWA can achieve a larger ablation zone (AZ); however, no evaluation has been performed to assess the influence of proximal or distal embolization on AZ. Material and Methods: Using a transgenic porcine liver tumor model, angiography and embolization of HT were performed with lipiodol or different-sized particles, ranging from 40 to 1200 µm to complete vascular occlusion followed by MWA for 4 min at 65 watts with subsequent ex vivo assessment of AZ. Results: AZ volume using 40 µm, 100 µm, and 300–500 µm microparticles were significantly larger than for the control, non-embolization group (mean ± standard deviation: 40 µm: 17.48 cm3 ± 1.22, P ≤ 0.001; 100 µm: 14.81 cm3 ± 0.43, P ≤ 0.001; and 300–500 µm: 12.16 cm3 ± 0.8, P ≤ 0.001 compared to 6.06 cm3 ± 2.02 in the control group. Conclusion: Distal embolization with smaller particles produced significantly larger AZ in an in vivo liver tumor when compared to no embolization control, lipiodol, or proximal large particle embolization.

Noncontrast MRI Surveillance of Craniopharyngiomas Using a Balanced Steady-state Free Precession (bSSFP) Sequence.

Contrast-enhanced MRI (CEMRI) is a commonly used imaging technique for craniopharyngioma surveillance; however, it carries risks such as allergic reaction and gadolinium deposition. This study evaluates the efficacy of non contrast-enhanced MRI (NCMRI) with a balanced steady-state free precession (bSSFP) sequence compared with CEMRI T1-weighted imaging for craniopharyngioma surveillance. Twenty-nine patients with craniopharyngioma (16 females/13 males, mean age =21.5 ± 4.3 years) with CEMRIs, including a bSSFP sequence, were evaluated. For each patient, 2 blinded neuroradiologists compared the dimensions of residual craniopharyngioma on non-contrast- and contrast-enhanced sequences. Tumor volume and solid/cystic component measurements were evaluated by using paired t-tests. Diagnostic confidence levels for non-contrast- and contrast-enhanced evaluations were measured by using a 3-point scale (2 = confident, 1 = adequate, 0 = unsure). Analyses of tumor involvement of cranial nerves (CNs) and adjacent vasculature and diagnostic confidence were performed by using Fisher exact and chi-square tests. No significant difference was observed between residual tumor volumes in both studies (18.86 ± 21.67 cm3 versus 17.64 ± 23.85 cm3, P = .55) and measurements of dominant solid component volume, number of cystic components, and largest cystic component volume (2.71 ± 3.47 cm3 versus 3.95 ± 5.51 cm3, P = .10; 2.5 ± 1.5 versus 2.9 ± 1.5, P = .10; 7.61 ± 13.41 versus 6.84 ± 13.37 cm3, P = .22, respectively). Tumor involvement of CNs II (P = .64), III (P = .42), and adjacent vasculature (P = .05) showed no significant differences in detection. Diagnostic confidence was comparable in evaluating CN II, vascular structures, and third ventricle (P > .05) involvement. Higher levels of confidence were observed with bSSFP sequences for the detection of CN III involvement (P = .0001) and with contrast-enhanced T1-weighted imaging for cavernous sinus involvement (P = .02). NCMRI techniques by using a bSSFP sequence provide similar characterization of craniopharyngiomas as contrast-enhanced techniques.

Multicompartment duct platform to study epithelial-endothelial crosstalk associated with lung adenocarcinoma.

Previous lung-on-chip devices have facilitated significant advances in our understanding of lung biology and pathology. Here, we describe a novel lung-on-a-chip model in which human induced pluripotent stem cell-derived alveolar epithelial type II cells (iAT2s) form polarized duct-like lumens alongside engineered perfused vessels lined with human umbilical vein endothelium, all within a 3D, physiologically relevant microenvironment. Using this model, we investigated the morphologic and signaling consequences of the KRASG12D mutation, a commonly identified oncogene in human lung adenocarcinoma (LUAD). We show that expression of the mutant KRASG12D isoform in iAT2s leads to a hyperproliferative response and morphologic dysregulation in the epithelial monolayer. Interestingly, the mutant epithelia also drive an angiogenic response in the adjacent vasculature that is mediated by enhanced secretion of the pro-angiogenic factor soluble uPAR. These results demonstrate the functionality of a multi-cellular in vitro platform capable of modeling mutation-specific behavioral and signaling changes associated with lung adenocarcinoma.

#2781 Renal cortical necrosis—a rare cause of acute kidney injury

Abstract Background and Aims Renal cortical necrosis (RCN) is a rare and catastrophic cause of acute kidney injury (AKI). It is characterized by ischemic destruction of all the elements of renal cortex due to marked reduction in renal arterial perfusion of renal cortex due to vascular spasm and microvascular injury. It can be patchy or diffuse depending upon the cause and extent of hypoperfusion. Snake bite is rare cause of RCN. Incidence of RCN following snake bite has been reported to be as high as in 25% of the bitten patients to <1%. Lack or delay in receiving anti snake venom (ASV) has been observed to be a contributing factor in development of RCN following snake bite. Method A 45-year-old female had an unknown bite on foot while returning to home at twilight. She had intense pain at site of bite with slight ooze of blood. Overnight she had vomiting and pain abdomen. Subsequently she developed progressive fall in urine output and dyspnoea. After about 36 hours of bite at the time of admission in hospital she had anuria, prolonged whole blood clotting time, tachypnoea, hypoxemia and required oxygen (O2) to maintain normal O2 saturation. She was given two doses of polyvalent ASV 6 hours apart which corrected her coagulation defect. Investigations showed: haemoglobin—9 gm/dl, total leucocyte count—18700/mcl, platelet—1.15 lakh/mcl, blood urea—88 mg/dl and serum creatinine—10.5 mg/dl. She was managed with haemodialysis and supportive care. Even after 3 weeks of onset of AKI, she had anuria so a kidney biopsy was done. Results kidney biopsy on light microscopy examination showed 9 glomeruli; 8 revealing global tuft necrosis along with necrosis of adjacent tubules and vasculature and necrotic process affected around 60% of sampled cortical area consistent with cortical necrosis (Fig. 1). She was continued with haemodialysis support and urine output and pre-dialysis serum creatinine were monitored. Her urine output after 3 months of onset of AKI is around one litre per day but her pre-dialysis serum creatinine stays in the range of 9-10 mg/dl and so she continues to receive biweekly haemodialysis. Conclusion In our index case, there was delay in getting ASV which may have contributed to development of RCN. So, early treatment of snake bite is important to prevent this catastrophic complication.

Inner Choroidal Fibrosis: An Optical Coherence Tomography Biomarker of Severity in Chronic Central Serous Chorioretinopathy

To describe a potential biomarker termed as inner choroidal fibrosis in cases of chronic central serous chorioretinopathy (CSCR) presenting to a tertiary referral center. Observational case series. Five eyes of 4 patients with CSCR were noted to have a gray-white subretinal lesion in the macula, which was analyzed with multimodal imaging. The lesions were hypofluorescent on autofluorescence, fundus fluorescein angiography, and indocyanine angiography. In all cases, a characteristic heterogeneous, hyperreflective lesion in the inner choroid was seen on optical coherence tomography (OCT), corresponding to the white subretinal lesions. The lesion was distinct from the adjacent choroid, with greater reflectivity and greater thickness than the adjacent compressed choroidal vasculature. The dilated outer pachyvessels were pushed outward or sideways in all cases. On OCT-angiography, the corresponding lesion showed flow void areas. We have termed this zone of inner choroidal hyperreflectivity "inner choroidal fibrosis." Upon analyzing the clinical course, 3 of the patients had a history of choroidal neovascularization. The contralateral eye in 2 of these 3 patients also developed choroidal neovascularization. Three of the eyes had an overlying focal choroidal excavation. We report a potential biomarker of CSCR termed "inner choroidal fibrosis" in 4 cases of chronic CSCR. It can best be identified on enhanced depth or swept source OCT as a region of heterogeneous hyperreflectivity in the inner choroid. This fibrosis could be regarded as a degenerative process secondary to more severe disease in the past.

Cross-talks between perivascular adipose tissue and neighbors: multifaceted nature of nereids.

Perivascular adipose tissue (PVAT) is a unique fat depot surrounding blood vessels and plays a vital role in the progression of vascular remodeling and dysfunction. PVAT exhibits remarkable differences in structure, phenotype, origin, and secretome across anatomical locations. The proximity of PVAT to neighboring vascular beds favors a niche for bidirectional communication between adipocytes and vascular smooth muscle cells, endothelial cells, and immune cells. In this review, we update our understanding of PVAT's regional differences and provide a comprehensive exploration of how these differences impact cross-talks between PVAT and the vascular wall. Different PVAT depots show different degrees of vasoprotective function and resilience to pathological changes such as obesity and vasculopathies, shaping multifaceted interactions between PVAT depots and adjacent vasculatures. The depot-specific resilience may lead to innovative strategies to manage cardiometabolic disorders.

A Rare Autopsy Case of Aggressive Combined Hepatocellular-Cholangiocarcinoma with Stem Cell Features in A 59-Year-Old Female

Abstract Introduction/Objective Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a rare liver tumor with histologic and phenotypic features of both hepatocellular carcinoma and intrahepatic cholangiocarcinoma. It is believed to arise from hepatic progenitor cells. It consists of intermingled malignant biliary and hepatic tissue and thus is a distinct entity, rather than two separate coexisting malignancies. Methods/Case Report A 59-year-old female with a history of hepatitis C and cirrhosis presented with abdominal pain, shortness of breath, and altered mental status. She developed hematemesis and went into cardiac arrest. Massive transfusion and cardiopulmonary resuscitation were initiated. She was intubated, and an esophageal/gastric balloon was placed. She then underwent a procedure to relieve portal hypertension and related gastrointestinal bleeding. Despite extensive interventions, her condition continued to deteriorate. She expired one day after her initial presentation. Results (if a Case Study enter NA) At autopsy, the liver was diffusely and markedly fibrotic with numerous nodules of varying size with invasion into adjacent vasculature. Microscopic examination of the nodules revealed cHCC-CC with stem cell features and lymphovascular invasion. Further examination revealed tumor emboli scattered throughout the right lung. The patient’s history of chronic hepatitis C may have contributed to the development of her cHCC-CC. Although gross appearance resembled cirrhosis, upon microscopic inspection the nodules showed excessive tumor burden. Ultimately the patient had end stage liver disease due to the accumulation of damage and consequent fibrosis. This led to portal hypertension with subsequent massive gastrointestinal bleeding, hemorrhagic shock, and death. Conclusion cHCC-CC is a rare aggressive primary liver tumor with a poor prognosis. It can present with a cirrhotomemetic pattern with small nodules that can evade clinical and radiographic detection. Autopsy findings can provide valuable insights into the pathogenesis and clinical course of cHCC-CC, highlight the aggressive nature of the disease, and may inform future diagnostic and therapeutic strategies. Accurate diagnosis of this tumor is important for patient management and prognostication.

An attention residual u-net with differential preprocessing and geometric postprocessing: Learning how to segment vasculature including intracranial aneurysms.

Intracranial aneurysms (IA) are lethal, with high morbidity and mortality rates. Reliable, rapid, and accurate segmentation of IAs and their adjacent vasculature from medical imaging data is important to improve the clinical management of patients with IAs. However, due to the blurred boundaries and complex structure of IAs and overlapping with brain tissue or other cerebral arteries, image segmentation of IAs remains challenging. This study aimed to develop an attention residual U-Net (ARU-Net) architecture with differential preprocessing and geometric postprocessing for automatic segmentation of IAs and their adjacent arteries in conjunction with 3D rotational angiography (3DRA) images. The proposed ARU-Net followed the classic U-Net framework with the following key enhancements. First, we preprocessed the 3DRA images based on boundary enhancement to capture more contour information and enhance the presence of small vessels. Second, we introduced the long skip connections of the attention gate at each layer of the fully convolutional decoder-encoder structure to emphasize the field of view (FOV) for IAs. Third, residual-based short skip connections were also embedded in each layer to implement in-depth supervision to help the network converge. Fourth, we devised a multiscale supervision strategy for independent prediction at different levels of the decoding path, integrating multiscale semantic information to facilitate the segmentation of small vessels. Fifth, the 3D conditional random field (3DCRF) and 3D connected component optimization (3DCCO) were exploited as postprocessing to optimize the segmentation results. Comprehensive experimental assessments validated the effectiveness of our ARU-Net. The proposed ARU-Net model achieved comparable or superior performance to the state-of-the-art methods through quantitative and qualitative evaluations. Notably, we found that ARU-Net improved the identification of arteries connecting to an IA, including small arteries that were hard to recognize by other methods. Consequently, IA geometries segmented by the proposed ARU-Net model yielded superior performance during subsequent computational hemodynamic studies (also known as "patient-specific" computational fluid dynamics [CFD] simulations). Furthermore, in an ablation study, the five key enhancements mentioned above were confirmed. The proposed ARU-Net model can automatically segment the IAs in 3DRA images with relatively high accuracy and potentially has significant value for clinical computational hemodynamic analysis.

Applications of Cinematic Rendering in the Diagnoses of Compressive Complications of Saphenous Venous Graft Pseudoaneurysms: A Pictorial Essay

Pseudoaneurysms arising from the saphenous venous graft (SVGs) are an uncommon complication of the coronary artery bypass graft (CABG). Although angiography is the gold standard, computed tomography angiography (CTA) of the coronary arteries is the most efficient modality to diagnose these cases and their associated complications. Among numerous possible complications of SVG pseudoaneurysms, local mass effect on the cardiac chambers, adjacent pulmonary vasculature or coronary arteries/bypass grafts have been described. Cinematic rendering, an advanced post-processing technique can be valuable for problem solving in complex cases. In this pictorial essay, we report 3 CT cases of SVG pseudoaneurysms that demonstrate a range of CT imaging appearances of SVG pseudoaneurysms and related complications. Additionally, we will emphasize the applications of cinematic rendering in visualization of complex post-surgical cardiovascular pathology. This manuscript is designed as a pictorial essay of 3 complex cases given the relative uncommon nature of this pathology and the availability of cinematic rendering as an advanced post-processing modality. We demonstrated 3 imaging examples of utilization of cinematic rendering (CR) to demonstrate complex anatomical details of the mass-effect and compression related complications associated with SVG pseudoaneurysms. A side-by-side comparison with conventional volume rendering (VR) is also performed in 1 case for perspective and to show improved comparative visual appeal of the CR given better depth perception and more natural appearing illumination. The technical differences of the 2 techniques are also briefly discussed.

3D mapping of phrenic nerve course for radiofrequency pulmonary vein isolation.

Phrenic nerve (PN) injury is a rare but severe complication of radiofrequency (RF) pulmonary vein isolation (PVI). The objective of this study was to characterize the typical intracardiac course of the PN with a three-dimensional electroanatomic mapping system, to quantify the need for modification of the ablation trajectory to avoid delivering an ablation lesion on sites with PN capture, and to identify very circumscribed areas of common PNC on the routine ablation trajectory of a RF-PVI, allowing fast and effective PN screening for everyday usage. We enrolled 137 consecutive patients (63 ± 9 years, 64% men) undergoing PVI. A detailed high output (20 mA) pace-mapping protocol was performed in the right (RA) and left atrium (LA) and adjacent vasculature. The right PN was most commonly captured in the superior vena cavaat a lateral (50%) or posterolateral (23%) position before descending along the RA either straight (29%) or with a posterolateral bend (20%). In the LA, beginning deep within the right superior pulmonary vein (RSPV), the right PN is most frequently detectable anterolateral (31%), then descends to the lateral proximal RSPV (23%), and further towards the lateral antral region (15%) onto the medial LA wall (12%). To avoid delivering an ablation lesion on sites with PN capture, modification of ablation trajectory was necessary in 23% of cases, most commonly in the lateral RSPV antrum (81%). No PN injury occurred. PN mapping frequently reveals the close proximity of the PN to the ablation trajectory during PVI, particularly in the lateral RSPV antrum. Routine PN pacing should be considered during RF PVI procedures.

S2620 Marginal Artery of Drummond Pseudoaneurysm Masquerading as Fistulous Tract Resulting in Recurrent Lower Gastrointestinal Bleeding

Introduction: The mortality rate of patients hospitalized with a lower gastrointestinal bleed has been reported at 1.1% in the United States from 2005 to 2014. Pseudoaneurysms, typically associated with pancreatitis, have been described in case reports as a rare condition with a small subset presenting as gastrointestinal bleeding. Our study describes a rare case of recurrent lower gastrointestinal bleeding diagnosed as a pseudoaneurysm by endoscopy and angiography. Case Description/Methods: A 38-year-old male presented to our facility from a long-term care facility with hematochezia and blood clots per gastrostomy-jejunostomy. He had recently been hospitalized for severe coronavirus disease 2019 with a complicated hospital course in the intensive care unit including necrotizing pancreatitis with an abdominal drain, multiple secondary infections, tracheostomy, and percutaneous endoscopic gastrostomy-jejunostomy. On previous hospitalization, he was found to have a small pseudoaneurysm of the gastroduodenal artery and received embolization of the gastroduodenal and gastroepiploic arteries at that time. During transport to our hospital, he was noted to have tachycardia, hypotension requiring norepinephrine, and was transfused one unit of red blood cells. Hemoglobin at this time was 7.5 g/dl after transfusion. Esophagogastroduodenoscopy was completed and showed a gastrojejunostomy tube in the expected location but was noted to be tight to the mucosa, which was pale in appearance. Flexible sigmoidoscopy revealed localized areas of edematous and erythematous mucosa with some associated oozing throughout the sigmoid colon. Repeat evaluation was completed one week later due to recurrent hematochezia. Colonoscopy was performed with identification of an apparent fistulous tract in the sigmoid colon located at 35 cm. Computed tomography angiography localized a pseudoaneurysm arising from the marginal artery of Drummond just proximal to its anastomosis with the ascending branch of the left colic artery and was successfully embolized. Discussion: Pseudoaneurysms, such as the one described in this case, have been shown to be associated with pancreatitis and can result if a pseudocyst involves adjacent vasculature. Gastrointestinal bleeding is a rare presentation of this condition. However, this case highlights the importance of repeat colonoscopy and angiography in the setting of a lower gastrointestinal bleed of unknown etiology.

Peripapillary Vessel Density in Relation to Optic Disc Drusen: A Multimodal Optical Coherence Tomography Study.

Optic disc drusen (ODD) are acellular calcified deposits within the optic nerve head known to cause visual field defects. An emerging gold standard for the diagnosis of ODD is enhanced depth imaging optical coherence tomography (EDI-OCT). The presence of ODD affects the adjacent peripapillary vasculature, which can be visualized using OCT angiography (OCTA). This study investigates the association between peripapillary vessel density and anatomical ODD location and volume using a newly developed method of multimodal OCT. A case-control study with 16 patients diagnosed with ODD in the period 2008-2017 and 24 healthy controls. All patients and controls had EDI-OCT, OCTA, and demographic data collected. Using EDI-OCT and the medical imaging segmentation tool ITK-SNAP, 3-dimensional (3D) visualization of ODD in patients were created. ODD 3D visualization and corresponding OCTA scans were superimposed, making it possible to correlate ODD volume to the peripapillary vessel density in the corresponding modified Garway-Heath segments of the optic disc. We found that mean peripapillary vessel density across all modified Garway-Heath segments were lower in ODD patients compared with controls with significant reduction of peripapillary vessel density in the superior segment ( P = 0.03) and globally ( P = 0.05). A significant inverse proportionality between ODD volume and peripapillary vessel density in the corresponding segment was seen ( P = 0.002). We found a reduced peripapillary vessel density in regions with close anatomical proximity to ODD and inverse proportionality between ODD volume and peripapillary vessel density.

Microvascular Decompression for Hypoglossal Nerve Palsy Associated With Vertebral Artery: Case Report and Review of Literature

BACKGROUND AND IMPORTANCE: Hypoglossal nerve palsy is an infrequent condition that could be rarely caused by compression from nearing vasculature. Hypoglossal nerve palsy associated with vertebral artery (VA) is rarely reported. There are less than 15 cases of such conditions in the literature. CLINICAL PRESENTATION: We present a 17-year-old boy suffering from dysarthria, chewing disability, a tingling sensation, and deviation of the tongue to the right from 6 months ago. After a thorough examination, MRI was performed with clinical suspicion of hypoglossal nerve palsy, and the result showed an ectatic VA pressing against the right hypoglossal nerve. He underwent microvascular decompression surgery. On follow-up visits, he showed gradual improvement of symptoms. CONCLUSION: In cases of cranial nerve palsies, compression by adjacent vasculature should be considered as a differential diagnosis and microvascular compression should be considered as a safe definitive treatment.

Photorealistic Depiction of Intracranial Tumors Using Cinematic Rendering of Volumetric 3T MRI Data

Cinematic Rendering (CR) incorporates a complex lightning model that creates photorealistic models from isotropic 3D imaging data. The utility of CR in depicting volumetric MRI data for pre-therapeutic planning is discussed, with intracranial tumors as a demonstrative example. We present a series of Cinematically Rendered intracranial tumors and discuss their utility in multidisciplinary pre-therapeutic evaluation. Isotropic, high-resolution, volumetric MRI data was collected, and CR was performed utilizing a proprietary application, "Anatomy Education" Siemens, Munich, Germany. Discrimination of cortex to white matter, brain surface to vessels, subarachnoid space to cortex and skull to intracranial structures was achieved and optimized by using various display settings on the Anatomy education application. Progressive removal of tissue layers allowed for a comprehensive assessment of the entire region of interest. Complex, small structures were demonstrated in very high detail. The depth and architecture of the sulci was appreciated in a format that more closely mimicked gross pathology than traditional imaging modalities. With appropriate display settings, the relationship of the cortical surface to the adjacent vasculature was also delineated. CR depicts the anatomic location of brain tumors in a format that depicts the relative proximity of adjacent structures in all dimensions and degrees of freedom. This allows for better conceptualization of the pathology and greater ease of communication between radiologists and other clinical teams, especially in the context of pretherapeutic planning.

Surgical Outcome of Vascular Resection and Reconstruction for Perihilar Cholangiocarcinoma

Introduction: Perihilar cholangiocarcinoma (pCCA) is an intractable malignancy and often involves the adjacent vasculature. To achieve radical resection, hepatectomy combined with vascular resection is required. This study aims to investigate short- and long-term outcome of vascular resection for pCCA. Methods: We retrospectively reviewed 201 consecutive patients with pCCA who underwent surgical resection between October 2013 to December 2018. The patients were grouped into the no vascular resection (NVR) (n=139) and vascular resection (VR) (n=62); PVR (n=47) and HAR with or without PVR (n=15). Results: The incidence of vascular resection in pCCA was 30.85%; PVR 23.38% and HAR 7.46%. The VR group had more postoperative major complications and 90-day mortality than the NVR group (28.9% vs 51.6%, p=0.002 and 7.9% vs 19.4%, p=0.029, respectively), but there was no difference between PVR and HAR group. The VR had a considerably greater number of advanced tumors than the NVR in terms of the AJCC staging classification. The VR had a worse median survival time than the NVR (14.8 vs 6.5 months; p=0.001), but there was no difference between the PVR and the HAR (6.5 vs 6.1 months; p=0.83). Positive resection margin, LN metastasis, and distant metastases were all significant prognostic factors in multivariable analysis. Conclusion: Patients with pCCA who had VR had worse short- and long-term outcomes than those who did not. The VR group, on the other hand, had a higher tumor grade than the NVR group, necessitating the utilization of a multidisciplinary team to treat them. Tabled 1EP03A-002CharacteristicsUnivariableMultivariableNMST (months)p-valueHR95%CIp-valueBismuth type0.0051.500.997-2.2650.052 1-316613.8 4326.5pT stage (AJCC 8th)0.0011.010.686-1.4960.949 pT 1,211115.2 pT 3,4879.0pN stage (AJCC 8th)<0.0012.241.469-3.401<0.001 pN 09822.9 pN 1/21005.2pM stage (AJCC 8th)<0.0012.441.235-4.8300.01 pM 018812.7 pM 1103.4Stage (AJCC 8th)<0.0011.230.718-2.1020.453 Stage 1,25227.0 Stage 3,41468.0Resection margin status<0.0012.892.006-4.161<0.001 Negative10624.5 Positive925.7PVR0.0011.260.875-1.8260.211 Absent14314.8 Present556.5HAR0.09 Absent18312.2 Present156.1 Open table in a new tab

The Evolution of 5-Aminolevulinic Acid Fluorescence Visualization: Time for a Headlamp/Loupe Combination

The use of 5-aminolevulinic acid (5-ALA) for intraoperative protoporphyrin IX fluorescent imaging in the resection of malignant gliomas has been demonstrated to improve tumor visualization, increase the extent of resection, and extend progression-free survival. The current technique for visualization of 5-ALA consists of excitation and emission filters built into the operating microscope. However, there are notable limitations to this process, including low quantum yield, expense, and masking of surrounding anatomy. We present 3 cases in which 3 separate methods were employed for visualizing fluorescence. The devices reported are 1) a low-cost blue light flashlight, 2) a low-cost headlamp, and 3) the first reported case of the new Designs for Vision REVEAL Fluorescence-Guided Surgery (FGS) 5-ALA fluorescent headlight and loupes. The aim of the study is to provide confirmation that tumor fluorescence can be observed using commercially available products other than the microscope. We demonstrate through 3 intraoperative cases that a variety of devices can produce visible fluorescence of the high-grade tumor and allow for simultaneous real-time visualization of the adjacent brain parenchyma and vasculature. The REVEAL FGS system appears to offer increased fluorescence emission compared with all other methods, including the microscope. Our study demonstrates the feasibility of using blue/ultraviolet light supplied by a commercially available, inexpensive flashlight or headlamp to visualize 5-ALA fluorescence in high-grade gliomas. We also provide the first documentation of the intraoperative use of the new Designs for Vision REVEAL FGS 5-ALA fluorescent headlight and loupes and report on the experience. Lack of an operative microscope capable of fluorescent illumination should not be a limiting factor in performing fluorescent-guided glioma resection.

Irreversible electroporation for pancreatic cancer using intraprocedural cone-beam computed tomography fusion navigation: a case report

BackgroundPatients diagnosed with locally advanced pancreatic cancer are usually not eligible for surgical resection because of significant vascular involvement. Stereotactic body radiation therapy and chemotherapy are the treatments recommended by the National Comprehensive Cancer Network criteria. For patients who do not respond to or tolerate stereotactic body radiation therapy and/or chemotherapy, a new option is irreversible electroporation. Irreversible electroporation is a nonthermal minimally invasive ablation technique that uses electrical pulses to induce apoptosis of tumor cells without damage to the extracellular matrix, thus preserving ducts and vessels. Irreversible electroporation requires very precise needle placement, which has limited its ubiquitous use. Intraprocedural cone-beam computed tomography with navigation can be fused with previous imaging to provide real-time tumor navigation capabilities during the procedure to allow for more accurate needle placement and treatment. Here, we present a patient who underwent percutaneous irreversible electroporation with intraprocedural cone-beam computed tomography fusion guidance to treat his pancreatic cancer.Case presentationThe patient, an 88-year-old White male, initially presented with abdominal pain, and was ultimately diagnosed with locally advanced pancreatic cancer. He has an excellent performance status and no other comorbidities. He was started on chemotherapy and radiation therapy, with good response. However, continued vascular involvement of the tumors precluded him from safe surgical resection. The patient underwent irreversible electroporation with intraprocedural cone-beam computed tomography fusion navigation. The primary lesion demonstrates no residual tumor, and the soft tissue involvement of the adjacent vasculature has stabilized.ConclusionsAlthough not curative on its own, irreversible electroporation holds promise as a treatment option for patients with locally advanced pancreatic cancer to increase downsizing to curative surgery or increase quality of life. Cone-beam computed tomography navigation can improve irreversible electroporation by providing guidance during needle guidance. Image fusion with previous advanced imaging can improve lesion visualization and targeting, thereby improving the effectiveness of irreversible electroporation.

Hypoxia-inducible Factor 2α: A Key Player in Tumorigenesis and Metastasis of Pheochromocytoma and Paraganglioma?

Germline or somatic driver mutations linked to specific phenotypic features are identified in approximately 70% of all catecholamine-producing pheochromocytomas and paragangliomas (PPGLs). Mutations leading to stabilization of hypoxia-inducible factor 2α (HIF2α) and downstream pseudohypoxic signaling are associated with a higher risk of metastatic disease. Patients with metastatic PPGLs have a variable prognosis and treatment options are limited. In most patients with PPGLs, germline mutations lead to the stabilization of HIF2α. Mutations in HIF2α itself are associated with adrenal pheochromocytomas and/or extra-adrenal paragangliomas and about 30% of these patients develop metastatic disease; nevertheless, the frequency of these specific mutations is low (1.6-6.2%). Generally, mutations that lead to stabilization of HIF2α result in distinct catecholamine phenotype through blockade of glucocorticoid-mediated induction of phenylethanolamine N-methyltransferase, leading to the formation of tumors that lack epinephrine. HIF2α, among other factors, also contributes importantly to the initiation of a motile and invasive phenotype. Specifically, the expression of HIF2α supports a neuroendocrine-to-mesenchymal transition and the associated invasion-metastasis cascade, which includes the formation of pseudopodia to facilitate penetration into adjacent vasculature. The HIF2α-mediated expression of adhesion and extracellular matrix genes also promotes the establishment of PPGL cells in distant tissues. The involvement of HIF2α in tumorigenesis and in multiple steps of invasion-metastasis cascade underscores the therapeutic relevance of targeting HIF2α signaling pathways in PPGLs. However, due to emerging resistance to current HIF2α inhibitors that target HIF2α binding to specific partners, alternative HIF2α signaling pathways and downstream actions should also be considered for therapeutic intervention.

Impact of Combined Vascular Resection and Reconstruction in Patients with Advanced Perihilar Cholangiocarcinoma

BackgroundPerihilar cholangiocarcinoma often involves the adjacent vasculature, including the portal vein and hepatic artery. Combined vascular resection and reconstruction of the portal vein is more common than vascular resection and reconstruction of the hepatic artery. Herein, we aimed to elucidate the long-term outcomes in patients who underwent vascular resection and reconstruction for perihilar cholangiocarcinoma. MethodsBetween January 2004 and December 2020, 106 patients with perihilar cholangiocarcinoma were grouped into the no resection (n = 58), resection-portal vein (n = 31), and resection-hepatic artery with or without that of portal vein (n = 17) groups. ResultsThere were no significant differences in morbidity and mortality between the three groups. The resection-portal vein and resection-hepatic artery groups had a significantly higher number of advanced tumors than the no resection group, but no significant differences were detected in the rates of lymph node metastasis and R0 resection between the three groups. The 5-year disease-specific survival in the resection-portal vein (37.6%) and resection-hepatic artery (26.9%) groups were poorer than that in the no resection group (47.8%), although the former groups had a significantly better prognosis than the latter group (7.0%). Multivariate analysis identified high preoperative carcinoembryonic antigen level (>5.7 ng/mL), intrahepatic metastasis, and non-R0 resection as independent poor prognostic factors. ConclusionAlthough the perioperative course in the resection-portal vein and hepatic artery groups was similar to that in the no resection group, the long-term prognoses were poor in the resection-portal vein and hepatic artery groups. Pre- and postoperative multidisciplinary therapy is required for patients with vascular resection and reconstruction.

Portal Vein Tumor Thrombus: No Longer a Death Sentence.

Hepatocellular carcinoma (HCC) is the most common malignancy of the liver and a leading cause of cancer mortality worldwide. HCC commonly results from longstanding liver cirrhosis, which presents a host of complications and a severely diminished quality of life. Despite advancements in diagnosis, molecular pathogenesis, and management of the complications associated with irreversible liver diseases, HCC remains an aggressive malignancy with high mortality. HCC is often invasive to adjacent vasculature, including the inferior vena cava (IVC) and portal veins, which present with rapid morbidity and patient decline. This article describes a patient with cirrhosis and HCC previously treated with cryoablation now presenting with multiple new foci and invasion of the left medial portal vein. These lesions were synchronously cryoablated. Cryoablation is typically reserved for solid tumor masses within the soft tissue or specific organs. This report illustrates a technique of directly cryoablating tumors within vessels. We achieved adequate cryoablation of the intravascular HCC portal vein tumor thrombus in the left medial portal vein. A one-month follow-up CT scan demonstrated significant portal vein macrovascular invasion (MVI) regression from 22.8 mm to 7.7 mm. Portal vein invasion by HCC presents unique challenges and traditionally precludes percutaneous or surgical therapy. Our technique shows successful cryoablation of MVI as a viable adjunct to treatment in select patients.