Multiscale and multimodal imaging for three-dimensional vascular and histomorphological organ structure analysis of the pancreas.

Exocrine and endocrine pancreas are interconnected anatomically and functionally, with vasculature facilitating bidirectional communication. Our understanding of this network remains limited, largely due to two-dimensional histology and missing combination with three-dimensional imaging. In this study, a multiscale 3D-imaging process was used to analyze a porcine pancreas. Clinical computed tomography, digital volume tomography, micro-computed tomography and Synchrotron-based propagation-based imaging were applied consecutively. Fields of view correlated inversely with attainable resolution from a whole organism level down to capillary structures with a voxel edge length of 2.0 µm. Segmented vascular networks from 3D-imaging data were correlated with tissue sections stained by immunohistochemistry and revealed highly vascularized regions to be intra-islet capillaries of islets of Langerhans. Generated 3D-datasets allowed for three-dimensional qualitative and quantitative organ and vessel structure analysis. Beyond this study, the method shows potential for application across a wide range of patho-morphology analyses and might possibly provide microstructural blueprints for biotissue engineering.

CT-guided High-Dose-Rate Brachytherapy versus Transarterial Chemoembolization in Patients with Unresectable Hepatocellular Carcinoma.

Background CT-guided high-dose-rate (HDR) brachytherapy (hereafter, HDR brachytherapy) has been shown to be safe and effective for patients with unresectable hepatocellular carcinoma (HCC), but studies comparing this therapy with other local-regional therapies are scarce. Purpose To compare patient outcomes of HDR brachytherapy and transarterial chemoembolization (TACE) in patients with unresectable HCC. Materials and Methods This multi-institutional retrospective study included consecutive treatment-naive adult patients with unresectable HCC who underwent either HDR brachytherapy or TACE between January 2010 and December 2022. Overall survival (OS) and progression-free survival (PFS) were compared between patients matched for clinical and tumor characteristics by propensity score matching. Not all patients who underwent TACE had PFS available; thus, a different set of patients was used for PFS and OS analysis for this treatment. Hazard ratios (HRs) were calculated from Kaplan-Meier survival curves. Results After propensity matching, 150 patients who underwent HDR brachytherapy (median age, 71 years [IQR, 63-77 years]; 117 males) and 150 patients who underwent TACE (OS analysis median age, 70 years [IQR, 63-77 years]; 119 male; PFS analysis median age, 68 years [IQR: 63-76 years]; 119 male) were analyzed. Hazard of death was higher in the TACE versus HDR brachytherapy group (HR, 4.04; P < .001). Median estimated PFS was 32.8 months (95% CI: 12.5, 58.7) in the HDR brachytherapy group and 11.6 months (95% CI: 4.9, 22.7) in the TACE group. Hazard of disease progression was higher in the TACE versus HDR brachytherapy group (HR, 2.23; P < .001). Conclusion In selected treatment-naive patients with unresectable HCC, treatment with CT-guided HDR brachytherapy led to improved OS and PFS compared with TACE. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Chapiro in this issue.

Short-term Outcomes of Robotic Versus Open Pancreatoduodenectomy: Propensity Score-matched Analysis.

OBJECTIVE: The goal of the current study was to investigate the perioperative outcomes of robotic pancreaticoduodenectomy (RPD) and open pancreaticoduodenectomy (OPD) in a high-volume center. BACKGROUND: Despite RPDs prospective advantages over OPD, current evidence comparing the 2 has been limited and has prompted further investigation. The aim of this study was to compare both approaches while including the learning curve phase for RPD. METHODS: A 1:1 propensity score-matched analysis of a prospective database of RPD with OPD (2017-2022) at a high-volume center was performed. The main outcomes were overall- and pancreas-specific complications. RESULTS: Of 375 patients who underwent PD (OPD n=276; RPD n=99), 180 were included in propensity score-matched analysis (90 per group). RPD was associated with less blood loss [500 (300-800) vs 750 (400-1000) mL; P =0.006] and more patients without a complication (50% vs 19%; P <0.001). Operative time was longer [453 (408-529) vs 306 (247-362) min; P <0.001]; in patients with ductal adenocarcinoma, fewer lymph nodes were harvested [24 (18-27) vs 33 (27-39); P <0.001] with RPD versus OPD. There were no significant differences for major complications (38% vs 47%; P =0.291), reoperation rate (14% vs 10%; P =0.495), postoperative pancreatic fistula (21% vs 23%; P =0.858), and patients with the textbook outcome (62% vs 55%; P =0.452). CONCLUSIONS: Including the learning phase, RPD can be safely implemented in high-volume settings and shows potential for improved perioperative outcomes versus OPD. Pancreas-specific morbidity was unaffected by the robotic approach. Randomized trials with specifically trained pancreatic surgeons and expanded indications for the robotic approach are needed.

3D stimulated Raman spectral imaging of water dynamics associated with pectin-glycocalyceal entanglement.

Pectin is a heteropolysaccharide responsible for the structural integrity of the cell walls of terrestrial plants. When applied to the surface of mammalian visceral organs, pectin films form a strong physical bond with the surface glycocalyx. A potential mechanism of pectin adhesion to the glycocalyx is the water-dependent entanglement of pectin polysaccharide chains with the glycocalyx. A better understanding of such fundamental mechanisms regarding the water transport dynamics in pectin hydrogels is of importance for medical applications, e.g., surgical wound sealing. We report on the water transport dynamics in hydrating glass-phase pectin films with particular emphasis on the water content at the pectin-glycocalyceal interface. We used label-free 3D stimulated Raman scattering (SRS) spectral imaging to provide insights into the pectin-tissue adhesive interface without the confounding effects of sample fixation, dehydration, shrinkage, or staining.

Real-Life Experience in the Treatment of Intrahepatic Cholangiocarcinoma by 90Y Radioembolization: A Multicenter Retrospective Study.

Limited treatment options in patients with intrahepatic cholangiocarcinoma (iCCA) demand the introduction of new, catheter-based treatment options. Especially, 90Y radioembolization may expand therapeutic abilities beyond surgery or chemotherapy. Therefore, the purpose of this study was to identify factors associated with an improved median overall survival (mOS) in iCCA patients receiving radioembolization in a retrospective study at 5 major tertiary-care centers. Methods: In total, 138 radioembolizations in 128 patients with iCCA (female, 47.7%; male, 52.3%; mean age ± SD, 61.1 ± 13.4 y) were analyzed. Clinical data, imaging characteristics, and radioembolization reports, as well as data from RECIST, version 1.1, analysis performed 3, 6, and 12 mo after radioembolization, were collected. mOS was compared among different subgroups using Kaplan-Meier curves and the log-rank test. Results: Radioembolization was performed as first-line treatment in 25.4%, as second-line treatment in 38.4%, and as salvage treatment in 36.2%. In patients receiving first-line, second-line, and salvage radioembolization, the disease control rate was 68.6%, 52.8%, and 54.0% after 3 mo; 31.4%, 15.1%, and 12.0% after 6 mo; and 17.1%, 5.7%, and 6.0% after 1 y, respectively. In patients receiving radioembolization as first-line, second-line, and salvage treatment, mOS was 12.0 mo (95% CI, 7.6-23.4 mo), 11.8 mo (95% CI, 9.1-16.6 mo), and 8.4 mo (95% CI, 6.3-12.7 mo), respectively. No significant differences among the 3 groups were observed (P = 0.15). Hepatic tumor burden did not significantly influence mOS (P = 0.12). Conclusion: Especially in advanced iCCA, second-line and salvage radioembolization may be important treatment options. In addition to ongoing studies investigating the role of radioembolization as first-line treatment, the role of radioembolization in the later treatment stages of the disease demands further attention.

Low bone mineral density is a prognostic factor for elderly patients with HCC undergoing TACE: results from a multicenter study.

OBJECTIVES: Low bone mineral density (BMD) was recently identified as a novel risk factor for patients with hepatocellular carcinoma (HCC). In this multicenter study, we aimed to validate the role of BMD as a prognostic factor for patients with HCC undergoing transarterial chemoembolization (TACE). METHODS: This retrospective multicenter trial included 908 treatment-naïve patients with HCC who were undergoing TACE as a first-line treatment, at six tertiary care centers, between 2010 and 2020. BMD was assessed by measuring the mean Hounsfield units (HUs) in the midvertebral core of the 11th thoracic vertebra, on contrast-enhanced computer tomography performed before treatment. We assessed the influence of BMD on median overall survival (OS) and performed multivariate analysis including established estimates for survival. RESULTS: The median BMD was 145 HU (IQR, 115-175 HU). Patients with a high BMD (≥ 114 HU) had a median OS of 22.2 months, while patients with a low BMD (< 114 HU) had a lower median OS of only 16.2 months (p < .001). Besides albumin, bilirubin, tumor number, and tumor diameter, BMD remained an independent prognostic factor in multivariate analysis. CONCLUSIONS: BMD is an independent predictive factor for survival in elderly patients with HCC undergoing TACE. The integration of BMD into novel scoring systems could potentially improve survival prediction and clinical decision-making. KEY POINTS: • Bone mineral density can be easily assessed in routinely acquired pre-interventional computed tomography scans. • Bone mineral density is an independent predictive factor for survival in elderly patients with HCC undergoing TACE. • Thus, bone mineral density is a novel imaging biomarker for prognosis prediction in elderly patients with HCC undergoing TACE.

Pediatric patient with a bilateral Salter-Harris II fracture and slipped capital femoral epiphysis secondary to autosomal recessive osteopetrosis.

Treatment of femoral neck fractures secondary to osteopetrosis is an uncertain and puzzled decision. Experience in the treatment, especially in the pediatric population, is scarcely reported. The duration of conservative treatment is prolonged and poses the risks of non-union and development of coxa vara deformity. The recommended treatment is closed reduction and internal fixation; however, surgery on osteopetrotic bone is challenging due to defective bone marrow function, delayed consolidation and higher risk of intraoperative fractures. Slipped capital femoral epiphysis secondary to osteopetrosis is very rarely reported. This article presents the case of a 5-year-old female patient with rapidly deteriorating physical function due to bilateral proximal femoral Salter-Harris type II fractures with associated slippage of the growth plates secondary to confirmed autosomal recessive osteopetrosis. Operative treatment was performed in a tertiary level orthopedic center with closed reduction and internal fixation with cannulated screws. A loss of fixation with coxa vara deformity was seen on the left side 7 months postoperatively with increasing pain. A revision surgery with reosteosynthesis and a valgus osteotomy was thus performed which showed good subjective and objective results 1 year postoperatively with complete bony union.

Tumor Burden in Patients With Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization: Head-to-Head Comparison of Current Scoring Systems.

Objectives: Recently, several scoring systems for prognosis prediction based on tumor burden have been promoted for patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE). This multicenter study aimed to perform the first head-to-head comparison of three scoring systems. Methods: We retrospectively enrolled 849 treatment-naïve patients with HCC undergoing TACE at six tertiary care centers between 2010 and 2020. The tumor burden score (TBS), the Six-and-Twelve score (SAT), and the Seven-Eleven criteria (SEC) were calculated based on the maximum lesion size and the number of tumor nodes. All scores were compared in univariate and multivariate regression analyses, adjusted for established risk factors. Results: The median overall survival (OS) times were 33.0, 18.3, and 12.8 months for patients with low, medium, and high TBS, respectively (p<0.001). The median OS times were 30.0, 16.9, and 10.2 months for patients with low, medium, and high SAT, respectively (p<0.001). The median OS times were 27.0, 16.7, and 10.5 for patients with low, medium, and high SEC, respectively (p<0.001). In a multivariate analysis, only the SAT remained an independent prognostic factor. The C-Indexes were 0.54 for the TBS, 0.59 for the SAT, and 0.58 for the SEC. Conclusion: In a direct head-to-head comparison, the SAT was superior to the TBS and SEC in survival stratification and predictive ability. Therefore, the SAT can be considered when estimating the tumor burden. However, all three scores showed only moderate predictive power. Therefore, tumor burden should only be one component among many in treatment decision making.

90Y Radioembolization in the Treatment of Neuroendocrine Neoplasms: Results of an International Multicenter Retrospective Study.

In neuroendocrine neoplasms (NENs), the presence of distant metastases has a severe impact on survival leading to a relevant decrease in the 5-y survival rate. Here, 90Y radioembolization (90Y RE) might be an important treatment option; however, data to support clinical benefits for 90Y RE are scarce. Therefore, the purpose of this study was to analyze the use of 90Y RE in NEN patients with hepatic metastases in an international, multicenter retrospective analysis and assess the potential role of 90Y RE in a multimodal treatment concept. Methods: In total, 297 angiographic evaluations in NEN patients before 90Y RE were analyzed. Baseline characteristics and parameters derived from imaging evaluation and 90Y RE were analyzed. Tumor response was assessed using RECIST 1.1, and survival data were collected. Mean overall survival (OS) between different groups was compared using Kaplan-Meier curves and the log rank test. A P value of less than 0.05 indicated statistical significance. Results: After 90Y RE, the disease control rate according to RECIST 1.1 was 83.5% after 3 mo and 50.9% after 12 mo. OS in the entire population was 38.9 ± 33.0 mo. High tumor grade (P < 0.006) and high tumor burden (P = 0.001) were both associated with a significant decrease in OS. The presence of extrahepatic metastases (P = 0.335) and the type of metastatic vascularization pattern (P = 0.460) had no influence on OS. Patients who received 90Y RE as second-line therapy had a slightly longer but not statistically significant OS than patients who had 90Y RE in a salvage setting (44.8 vs. 30.6 mo, P = 0.078). Hepatic and global progression-free survival after 90Y RE was significantly decreased in heavily pretreated patients, compared with patients with second-line therapy (P = 0.011 and P = 0.010, respectively). Conclusion:90Y RE could be an important alternative to peptide receptor radionuclide therapy as second-line treatment in patients with progressive liver-dominant disease pretreated with somatostatin analogs.

The impact of portal vein tumor thrombosis on survival in patients with hepatocellular carcinoma treated with different therapies: A cohort study.

BACKGROUND: Portal vein tumor thrombosis (PVTT) is a frequent complication of hepatocellular carcinoma (HCC), which leads to classification as advanced stage disease (regardless of the degree of PVTT) according to the Barcelona Clinic Liver Cancer Classification. For such patients, systemic therapy is the standard of care. However, in clinical reality, many patients with PVTT undergo different treatments, such as resection, transarterial chemoembolization (TACE), selective internal radiation therapy (SIRT), or best supportive care (BSC). Here we examined whether patients benefited from such alternative therapies, according to the extent of PVTT. METHODS: This analysis included therapy-naïve patients with HCC and PVTT treated between January 2005 and December 2016. PVTT was classified according to the Liver Cancer study group of Japan as follows: Vp1 = segmental PV invasion; Vp2 = right anterior or posterior PV; Vp3 = right or left PV; Vp4 = main trunk. Overall survival (OS) was analyzed for each treatment subgroup considering the extent of PVTT. We performed Cox regression analysis with adjustment for possible confounders. To further attenuate selection bias, we applied propensity score weighting using the inverse probability of treatment weights. RESULTS: A total of 278 treatment-naïve patients with HCC and PVTT were included for analysis. The median observed OS in months for each treatment modality (resection, TACE/SIRT, sorafenib, BSC, respectively) was 32.4, 8.1, N/A, and 1.7 for Vp1; 10.7, 6.9, 5.5, and 1.2 for Vp2; 6.6, 7.5, 2.9, and 0.6 for Vp3; and 8.0, 3.6, 5.3, and 0.7 for Vp4. Thus, the median OS in the resection group in case of segmental PVTT (Vp1) was significantly longer compared to any other treatment group (all p values <0.01). CONCLUSIONS: Treatment strategy for HCC with PVTT should not be limited to systemic therapy in general. The extent of PVTT should be considered when deciding on treatment alternatives. In patients with segmental PVTT (Vp1), resection should be evaluated.

Epithelial-to-Mesenchymal Transition in Pancreatic Cancer is associated with Restricted Water Diffusion in Diffusion-Weighted Magnetic Resonance Imaging.

Purpose: This study aimed to evaluate the potential of diffusion-weighted magnetic resonance imaging (DW-MRI) as imaging biomarker for epithelial-to-mesenchymal transition (EMT) in pancreatic ductal adenocarcinoma (PDAC). Methods: In forty-two patients, preoperative apparent diffusion coefficient (ADC) values of therapy-naive PDAC were compared with immunohistochemical expression profiles of the epithelial marker E-cadherin as well as mesenchymal transcription factors Runt-related transcription factor 2 (Runx2) and Zinc finger E-box-binding homeobox 1 (Zeb1), as determined by Allred immunoreactivity score. Results: We observed a significant positive rank correlation between the ADC and the E-cadherin Allred score (ρ = 0.553, p < 0.001) and significant negative rank correlations between the ADC and the Runx2 Allred score (ρ = -0.526, p < 0.001) as well as the Zeb1 Allred score (ρ = -0.710, p < 0.001). Compared to tumors with low ADC values < 1.3 µm2/s, tumors with ADC values ≥ 1.3 µm2/s had significantly higher Allred scores for E-cadherin (median, 4 versus 5; p < 0.001) and significantly lower Allred scores for Runx2 (median, 3 versus 2; p = 0.003) as well as Zeb1 (median, 4 versus 0; p < 0.001). Conclusion: In PDAC, tumor plasticity in terms of EMT is well reflected by ADC values from DW-MRI. In the near future, DW-MRI could be beneficial for identification of PDAC patients that might profit from personalized EMT-targeted therapies.

Diffusion Kurtosis Imaging-A Superior Approach to Assess Tumor-Stroma Ratio in Pancreatic Ductal Adenocarcinoma.

Extensive desmoplastic stroma is a hallmark of pancreatic ductal adenocarcinoma (PDAC) and contributes to tumor progression and to the relative resistance of tumor cells towards (radio) chemotherapy. Thus, therapies that target the stroma are under intense investigation. To allow the stratification of patients who would profit from such therapies, non-invasive methods assessing the stroma content in relation to tumor mass are required. In the current prospective study, we investigated the usefulness of diffusion-weighted magnetic resonance imaging (DW-MRI), a radiologic method that measures the random motion of water molecules in tissue, in the assessment of PDAC lesions, and more specifically in the desmoplastic tumor stroma. We made use of a sophisticated DW-MRI approach, the so-called diffusion kurtosis imaging (DKI), which possesses potential advantages over conventional and widely used monoexponential diffusion-weighted imaging analysis (cDWI). We found that the diffusion constant D from DKI is highly negatively correlated with the percentage of tumor stroma, the latter determined by histology. D performed significantly better than the widely used apparent diffusion coefficient (ADC) from cDWI in distinguishing stroma-rich (>50% stroma percentage) from stroma-poor tumors (≤50% stroma percentage). Moreover, we could prove the potential of the diffusion constant D as a clinically useful imaging parameter for the differentiation of PDAC-lesions from non-neoplastic pancreatic parenchyma. Therefore, the diffusion constant D from DKI could represent a valuable non-invasive imaging biomarker for assessment of stroma content in PDAC, which is applicable for the clinical diagnostic of PDAC.

Extent of portal vein tumour thrombosis in patients with hepatocellular carcinoma: The more, the worse?

BACKGROUND & AIMS: Portal vein tumour thrombosis (PVTT) has a significant impact on the prognosis of patients with hepatocellular carcinoma (HCC). The degree of PVTT varies from sub-/segmental invasion to complete occlusion of the main trunk. Aim of this study was to evaluate whether the degree of PVTT correlates with prognosis. METHODS: A total of 1317 patients with HCC treated at our tertiary referral centre between January 2005 and December 2016 were included. PVTT was diagnosed by contrast-enhanced computed tomography or magnetic resonance imaging. The extent of PVTT was documented according to the Liver Cancer Study Group of Japan classification: Vp0 = no PVTT, Vp1 = segmental portal vein invasion, Vp2 = right anterior/posterior portal vein, Vp3 = right/left portal vein and Vp4 = main trunk. Median overall survival (OS) was calculated for each group. RESULTS: Portal vein tumour thrombosis was present in 484 (36.8%) patients. Median OS without PVTT was 35.7 months, significantly longer than in patients with PVTT (7.2 months, P < 0.001). The patients with PVTT were subclassified as follows: 103 Vp1, 87 Vp2, 143 Vp3 and 151 Vp4. The corresponding median OS yielded 14.6, 9.4, 5.8 and 4.8 months for Vp1-Vp4, respectively (P < 0.001). CONCLUSIONS: Portal vein tumour thrombosis in patients with HCC is associated with a dismal prognosis. The results indicate an association between the extent of PVTT and OS. However, the extent of PVTT is not that decisive, as even minor PVTT leads to a very poor prognosis. Therefore, meticulous evaluation of cross-sectional imaging is crucial for the clinical management of patients with HCC.