
PURPOSE:Noninvasive scores have been proposed to identify patients with at-risk metabolic dysfunction-associated steatohepatitis (MASH) who may benefit from pharmacologic therapy. The LAD-NASH (model combining attenuation coefficient, dispersion slope, and liver stiffness for identification of nonalcoholic steatohepatitis) score, a multiparametric ultrasound (US)-based model that combines the attenuation coefficient, dispersion slope, and liver stiffness to identify nonalcoholic steatohepatitis, was recently developed for this purpose. This study aimed to validate the LAD-NASH score for identifying at-risk MASH in patients with biopsy-proven metabolic dysfunction-associated steatotic liver disease (MASLD) and to compare its diagnostic performance with that of the FibroScan-aspartate aminotransferase (FAST) score. METHODS:This study enrolled consecutive patients who underwent multiparametric US and liver biopsy on the same day between February 2023 and April 2024. At-risk MASH was defined as biopsy-confirmed MASH with a MASLD activity score of ≥4 and fibrosis stage of ≥F2. The diagnostic performance of the LAD-NASH and FAST scores was evaluated using the areas under the receiver-operating characteristic curves (AUROCs). RESULTS:A total of 70 patients with biopsy-proven MASLD were included (median age, 44 years; 34 men; median body mass index, 28.7 kg/m²; at-risk MASH, 27.1%). The LAD-NASH and FAST scores demonstrated comparable diagnostic performance for identifying at-risk MASH (AUROCs, 0.740; 95% confidence intervals [CI], 0.621 to 0.838 vs. 0.739; 95% CI, 0.621 to 0.837; P=0.995). Using the rule-out cutoff of ≤0.264, the LAD-NASH score demonstrated 100% sensitivity and 100% negative predictive value for at-risk MASH. CONCLUSION:The LAD-NASH and FAST scores showed comparable diagnostic performance for identifying at-risk MASH. Because it is based solely on multiparametric US, the LAD-NASH score may be a useful noninvasive rule-out tool for at-risk MASH.
PURPOSE:This study evaluated and compared energy consumption between automated breast ultrasound (ABUS) and handheld ultrasound (HHUS) systems during routine whole-breast ultrasound (US) examinations in clinical practice. METHODS:This prospective observational study included 320 consecutive patients who underwent breast US between July and October 2025. Four systems were used: two ABUS systems, designated ABUS-1 and ABUS-2, and two HHUS systems, designated HHUS-1 and HHUS-2. HHUS examinations were performed by four radiologists. Energy consumption was measured using a real-time power meter synchronized with system log files. Power consumption was analyzed in active, idle, and off modes. Average power in each mode, examination duration, and energy consumption during active scanning were calculated. Data were analyzed using the independent-samples t-test or Mann-Whitney U test with Bonferroni correction. RESULTS:In idle mode, ABUS systems consumed significantly less average power than HHUS systems (P<0.001). In off mode, both ABUS systems consumed 0 W, whereas HHUS systems continued to consume residual power. During active scanning, ABUS systems had shorter examination durations than HHUS systems, with ABUS-1 showing the shortest duration. Energy consumption during active scanning was lowest for ABUS-1, which consumed approximately 47% less energy than HHUS-1 (P<0.001). Across all radiologists, both ABUS systems consistently showed lower energy consumption than HHUS-1. CONCLUSION:Compared with HHUS, ABUS showed lower power use in idle and off modes and similar or lower energy consumption during active scanning. When clinically appropriate, preferential use of ABUS may improve energy sustainability while preserving clinical utility.
PURPOSE:High-risk esophageal varices (HREVs) are a serious complication of cirrhosis, and reliable noninvasive tools are needed to improve endoscopic triage. This study aimed to develop and validate an ultrasound-based model for predicting HREVs in patients with hepatitis-related cirrhosis. METHODS:This retrospective study included 293 patients who underwent endoscopy and noninvasive assessment between January 2019 and January 2023. Patients were assigned to training (n=210) and validation cohorts (n=83). Predictors were selected using univariable analysis, multivariable logistic regression, and Akaike information criterion-based backward selection. Discrimination, calibration, and clinical utility were evaluated using receiver operating characteristic analysis, calibration curves, decision curve analysis, and clinical impact curves. RESULTS:Portal vein velocity (PVV) and spleen volume (SV) were retained in the final model. The model incorporated PVV as a linear term and SV as a restricted cubic spline term. The area under the receiver operating characteristic curve was 0.951 in the training cohort and 0.956 in the validation cohort. At a cutoff of 0.30, the model showed high diagnostic performance and outperformed the single predictors and the Baveno VI criteria. Calibration and decision curve analyses indicated good agreement and favorable clinical utility. CONCLUSION:This model provides a simple, noninvasive approach to individualized prediction of HREVs in patients with hepatitis-related cirrhosis.
PURPOSE:This study aimed to assess the feasibility, safety, and preliminary oncologic outcomes of an adaptive radiofrequency ablation (RFA) strategy using the Octopus multipurpose (Octopus MP) electrode for small hepatocellular carcinoma (HCC) in anatomically challenging locations. Materials and. METHODS:This prospective, single-center cohort study enrolled 76 patients with 83 small HCCs (≤3 cm) in at-risk locations, including tumors adjacent to heat-sensitive organs, central bile ducts, or major vessels and tumors in capsule-adjacent or subphrenic locations. The Octopus MP electrode incorporates integrated temperature monitoring and a central 19-gauge multipurpose needle for fluid instillation and real-time temperature sensing. An anatomy-driven protocol allocated tumors to combined percutaneous ethanol injection plus RFA (PEI-RFA) or temperature-monitored RFA (TM-RFA). The primary endpoint was the thermal injury rate, and secondary endpoints included technical success, technique efficacy, and local tumor progression (LTP). RESULTS:The per-protocol analysis included 45 patients with 51 tumors in the PEI-RFA arm and 31 patients with 32 tumors in the TM-RFA arm. Technical success and 1-month technique efficacy were 100% in both arms. No major complications occurred. Thermal injury was observed in three of 45 patients (6.7%) in the PEI-RFA arm and two of 31 patients (6.5%) in the TM-RFA arm; all events were minor and self-limited. Late clinically insignificant biliary strictures occurred in four of 45 patients (8.9%) in the PEI-RFA arm and one of 31 patients (3.2%) in the TM-RFA arm. Patient-based cumulative LTP rates at 12, 24, and 36 months were 4.44%, 7.13%, and 10.95%, respectively, in the PEI-RFA arm and 3.23%, 3.23%, and 7.41%, respectively, in the TM-RFA arm. CONCLUSION:An anatomy-driven adaptive strategy using the Octopus MP electrode, which integrates established adjunctive ablation techniques within a single device, was feasible for small HCCs near critical structures and was associated with favorable safety and mid-term local control.
PURPOSE:This study aimed to evaluate shear-wave elastography (SWE)-derived stiffness values and key histopathologic features of soft-tissue sarcomas and to assess the potential diagnostic value of SWE for differentiating sarcomas from non-sarcoma soft-tissue lesions. METHODS:This retrospective study included 49 consecutive patients with clinically suspected soft-tissue tumors who underwent conventional ultrasonography (US) and SWE between April 2024 and March 2025. Quantitative SWE parameters, including mean and maximum stiffness values in kilopascals, were measured from at least four acquisitions for each lesion. Histopathologic grade was determined using the Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) system, and key histopathologic features relevant to SWE interpretation were assessed, including tumor necrosis, mitotic count, cellularity, and extent of myxoid stroma. Associations between SWE-derived stiffness values and histopathologic features were evaluated as the primary analysis, and diagnostic performance for sarcoma discrimination was evaluated as a secondary analysis. A P<0.05 was considered to indicate statistical significance. RESULTS:Microscopic necrosis was the only histopathologic feature significantly associated with SWE-derived stiffness; sarcomas without necrosis showed higher stiffness values than those with necrosis (P<0.05). SWE stiffness values showed a nonlinear relationship with FNCLCC grade, increasing from grade 1 to grade 2 and then decreasing in grade 3 sarcomas. Conventional US showed high sensitivity (84.4%) but low specificity (35.3%) for sarcoma discrimination, whereas SWE-derived stiffness showed low sensitivity (21.9%-31.3%) but relatively high specificity (82.4%-88.2%). CONCLUSION:SWE-derived stiffness appears to be affected by intratumoral heterogeneity, particularly microscopic necrosis, which may help explain its nonlinear relationship with histologic grade. Although SWE alone showed limited sensitivity for sarcoma discrimination, its relatively high specificity may complement conventional US when markedly elevated stiffness is present.
Ultrasound is the most widely used imaging modality for liver evaluation because it is accessible, portable, affordable, and repeatable. Quantitative liver ultrasound should therefore be understood not as a single technology, but as a set of biomarker strategies at different stages of development. Ultrasound elastography is the most mature component of this field and has been incorporated into noninvasive pathways for fibrosis assessment. Ultrasound-based liver fat quantification is also advancing rapidly through attenuation, backscatter, and radiofrequency-based techniques. A newer area of investigation involves the evaluation of viscoelasticity and inflammatory activity using shear-wave dispersion and related biomarkers, particularly in metabolic dysfunction-associated steatotic liver disease. The future value of quantitative liver ultrasound will depend on integrating multiple parameters to support clinical triage, monitoring, and, increasingly, treatment decision-making.
The purpose of this study was to present a standardized technical and methodological framework for functional ultrasound assessment of the subacromial space. This framework, the Functional Impingement Subacromial Ultrasound (FISUN) test, was designed to evaluate dynamic relationships between the greater tuberosity of the humerus and the acromion during functional arm elevation. The FISUN test is performed using real-time musculoskeletal ultrasound during functional arm elevation in the scapular plane under three sequential conditions with progressively increasing functional demands. The assessment is based on dynamic analysis of the relationship between the greater tuberosity of the humerus and the acromion during passive arm elevation, active arm elevation, and active arm elevation against resistance. A four-level classification system (levels 0-IV) is proposed to describe patterns of functional subacromial space behavior. The FISUN test provides a reproducible, clinically applicable framework for functional ultrasound assessment beyond static imaging and pain-provocation tests. By integrating standardized movement conditions with real-time dynamic ultrasound, the test allows subacromial space behavior to be evaluated in the context of motor control and functional loading. This Technical Note presents the methodological foundations of the FISUN test and provides a basis for future reliability studies.
PURPOSE:This study investigated the associations of prenatally diagnosed congenital heart disease (CHD) with head circumference (HC) and supratentorial brain structures, specifically the corpus callosum (CC) and subarachnoid space (SAS), and determined whether these measurements varied according to expected fetal brain oxygen delivery. METHODS:This prospective case-control study included 102 pregnancies at 32 to 36 weeks of gestation: 51 fetuses with CHD and 51 healthy controls. CHD cases were grouped according to expected fetal brain oxygen delivery as class A (n=26, reduced supply) or class B (n=25, normal supply). Measurements included CC length, the heights of the genu, body, and splenium, SAS, and HC. RESULTS:Gestational age at delivery and birth weight were significantly lower in the CHD group than in controls (both P<0.01). Total CC length and all segmental heights (genu, body, and splenium) were significantly reduced in both CHD subgroups (class A and class B) compared with healthy controls (all P<0.01). However, no significant differences in CC parameters were observed between class A and class B (P>0.99). SAS (P=0.267) and HC (P=0.083) measurements did not differ significantly among the three study groups. CONCLUSION:Fetuses with CHD exhibited significant structural reductions across all CC dimensions, independent of the expected cerebral oxygen delivery pattern, whereas global parameters (HC and SAS) did not differ significantly. These findings suggest that CHD-related prenatal brain alterations may involve white matter development even without measurable changes in global cranial parameters, supporting CC biometry as a potentially sensitive marker for early neurodevelopmental risk assessment.
PURPOSE:This study aimed to evaluate the clinical utility of different ultrasound-based methods for assessing growth in low-suspicion thyroid nodules and to determine whether significant nodule growth (SNG) is associated with malignancy or thyroid neoplasm, as well as its implications for follow-up intervals. METHODS:In this retrospective study, 309 patients with 334 low-suspicion thyroid nodules were analyzed. All nodules underwent at least three ultrasound examinations over ≥1 year and had cytopathologic confirmation. SNG was defined using three criteria: diameter-based criterion (DBC; ≥20% increase in at least two diameters with a minimum increase of ≥2 mm), volume-based criterion (VBC; ≥50% increase in volume), and change in the longest diameter alone (≥20% and ≥2 mm increase). Statistical associations between SNG and malignancy or thyroid neoplasm were evaluated using odds ratios (ORs). RESULTS:Nodule growth was common, occurring in 57.8% of nodules according to DBC or VBC and in 51.5% based on the longest diameter, with substantial concordance between methods (κ=0.68). The median time to SNG was 2.9 years for DBC or VBC and 2.6 years for the longest diameter. SNG was not significantly associated with malignancy (OR, 1.19; 95% confidence interval [CI], 0.69 to 2.06) or thyroid neoplasm (OR, 1.05; 95% CI, 0.59 to 1.88). CONCLUSION:Among cytopathologically confirmed low-suspicion thyroid nodules, SNG was not associated with malignancy or thyroid neoplasm. Measurement of the longest diameter alone provided a practical alternative to more complex growth assessment methods. Given that the median time to SNG exceeded 2.6 years, current ultrasound follow-up intervals for low-suspicion nodules may warrant cautious reconsideration.
PURPOSE:Conventional ultrasound-based bladder volumetry multiplies three orthogonal diameters and applies a heuristic shape coefficient. This approach requires near-simultaneous transverse and sagittal imaging and is vulnerable to interplane misregistration and coefficient-dependent bias. This study evaluated whether a single sagittal B-mode image can provide accurate, patient-specific bladder volume estimation by leveraging sagittal morphology, perivesical echotexture, and latent image features associated with overall bladder geometry. METHODS:In this Institutional Review Board-approved, single-center study, participants were scanned in the supine position, and bladder volume was referenced to immediate Foley catheter drainage. Segmentation masks were independently annotated by two sonographers and adjudicated by a urologist. Maximum sagittal length was extracted using OpenCV and included as an auxiliary scalar input. A single-stage deep learning model was developed that receives one sagittal B-mode image and its expert-annotated segmentation mask as input. The model used a lightweight convolutional neural network backbone with integrated self-attention to capture global echotextural cues. Performance on a held-out test set (n=53) was assessed using linear regression, Bland-Altman analysis, mean absolute error, and mean absolute percentage error. RESULTS:The model demonstrated a strong correlation with catheter-derived volumes (R²=0.87). Bland-Altman analysis showed a mean bias of -3.96±48.44 mL, with limits of agreement from -98.90 to +90.98 mL. Stratified error analysis showed a mean absolute error of 14.15 mL for volumes of 0-100 mL and a mean absolute percentage error of 16.64% for volumes ≥100 mL. Attention maps emphasized the bladder wall and perivesical soft tissues, suggesting reliance on contextual echotexture. CONCLUSION:A deep learning framework using a single sagittal plane estimated bladder volume with accuracy approaching that of two-plane techniques while simplifying image acquisition and eliminating reliance on fixed shape coefficients.
Ultrasound-guided fine needle aspiration biopsy (FNAB) for thyroid lesions has proven safe and effective; however, FNAB has limitations, including the frequent occurrence of nondiagnostic and inconclusive results and technical challenges in specific clinical scenarios. To address these limitations, core needle biopsy (CNB) was introduced, and substantial advancements have been made in CNB devices and techniques. Evidence from large patient cohorts indicates that CNB is not only safe and reliable but also provides superior diagnostic accuracy compared with FNAB. This review discusses recent advancements in CNB techniques to optimize tissue sampling, the diagnostic performance of CNB, and patient-centered perspectives, highlighting the potential of CNB as a selective first-line biopsy modality.
Super-resolution (SR) contrast-enhanced ultrasound (CEUS) is a novel sub-diffraction imaging modality that surpasses the diffraction limitations of conventional ultrasound and enables visualization of intricate microvascular architectures. SR CEUS provides improved quantification of hemodynamics and enhanced visualization of microvessels, thereby overcoming several inherent limitations of traditional CEUS. Initially demonstrated for imaging microvessels in the brains of small animals, SR CEUS has subsequently been investigated in multiple fields, including oncology, nephrology, and neurological research, with applications reported in breast cancer, chronic liver disease, and lymph node evaluation. However, clinical translation remains limited by prolonged acquisition times resulting from suboptimal microbubble detectability and the requirement for diluted contrast agents. This review summarizes the technical principles, clinical applications, current limitations, and future directions of SR CEUS from a clinical perspective.
PURPOSE:This study aimed to evaluate the diagnostic performance of vector flow imaging (VFI)-derived hemodynamic parameters and radiofrequency echo-tracking-derived arterial stiffness indices (RF-ASI) for detecting severe carotid artery stenosis. METHODS:This prospective, single-center observational study included 90 patients with carotid artery disease examined between May and July 2024. Stenosis severity was categorized as <50%, 50%-69%, and ≥70% according to the Society of Radiologists in Ultrasound (SRU) Doppler criteria. In patients with stenosis ≥50%, severity was confirmed using digital subtraction angiography, computed tomography angiography, or magnetic resonance angiography. At the plaque level, VFI-derived wall shear stress (WSS) and turbulence metrics, as well as RF-ASI, were measured. Correlation analyses, group comparisons, and receiver operating characteristic analysis were performed to evaluate each parameter's ability to detect ≥70% stenosis. RESULTS:Among the 90 patients (mean age, 70.4±8.7 years; 55.6% male), peak-segment mean wall shear stress (WSSmean) demonstrated the strongest correlation with stenosis severity (rₛ=0.87, P<0.001). WSSmean also showed the highest diagnostic performance for detecting ≥70% stenosis (area under the curve, 0.96; 95% confidence interval, 0.92 to 0.99; cutoff, 2.25 Pa), compared with other VFI-derived metrics and RF-ASI. Segmental analysis revealed that WSS values were highest at the plaque peak, whereas turbulence-related metrics were more pronounced in distal segments. In SRU-discordant cases (7 of 90), WSSmean agreed with anatomic imaging-based classification (≥70% vs. <70%) in six of seven lesions. CONCLUSION:VFI-derived WSSmean demonstrated the highest diagnostic performance for detecting severe (≥70%) carotid stenosis. In contrast, RF-ASI showed limited discriminatory ability and may primarily reflect global arterial stiffness rather than focal plaque severity.
PURPOSE:Patients with hypertriglyceridemia retain residual atherosclerotic risk despite achieving low-density lipoprotein cholesterol (LDL-C) targets. This study investigated the association of this risk with carotid stiffening assessed by ultrafast pulse wave velocity (ufPWV). METHODS:This study included 518 participants who underwent simultaneous ufPWV and carotid intima-media thickness (cIMT) measurements. Participants were stratified by triglyceride (TG) level into TG-optimal, TG-normal, and TG-high groups. Pulse wave velocity (PWV) at the beginning of systole and at the end of systole (PWV-ES) were measured using ufPWV. Participants were also categorized by Framingham risk score (FRS) into low-, intermediate-, and high-risk subgroups and by LDL-C level into normal and high subgroups. Logistic regression analysis was used to evaluate the potential predictive role of increased PWV-ES. RESULTS:In the total population and the normal LDL-C subgroup, both the TG-high and TG-normal groups had higher PWV-ES and cIMT values than the TG-optimal group (all P<0.05). Among participants with normal cIMT (<0.050 cm), PWV-ES effectively differentiated the TG-optimal and TG-high groups (P<0.001), but this difference was not observed when cIMT was ≥0.050 cm. Similarly, PWV-ES differentiated TG groups within the low-risk FRS subgroup (all P<0.01), but not within the intermediate- or high-risk subgroups. Logistic regression showed that increased PWV-ES was independently associated with high TG levels in both the normal LDL-C subgroup (odds ratio [OR], 1.21; P=0.006) and the high LDL-C subgroup (OR, 1.57; P=0.023) after adjustment for LDL-C alone. CONCLUSION:ufPWV-quantified carotid stiffness is associated with elevated TG-driven residual atherosclerotic risk, independent of LDL-C.
Purpose This study aimed to evaluate the utility of the Kupffer phase in Sonazoid-enhanced ultrasonography (SZUS) for liver tumor ablation and to identify factors influencing tumor conspicuity on the Kupffer phase. Methods Eighty-one patients with 128 liver tumors (95 hepatocellular carcinomas [HCCs] and 33 non-HCCs) who underwent gadoxetic acid–enhanced magnetic resonance imaging (MRI), B-mode planning ultrasonography (B-US), and SZUS-guided radiofrequency ablation (RFA) were included. Two radiologists scored tumor conspicuity on the hepatobiliary phase (HBP) of MRI, B-US, and the Kupffer phase using a 4-point scale. Tumor echogenicity on B-US was classified as hypoechoic or non-hypoechoic. This study analyzed tumor conspicuity across modalities, correlations between modalities, RFA technical success rates, and predictors of high Kupffer phase conspicuity. Results The mean tumor diameter was 14.2±7.0 mm, with no differences in size or location between HCCs and non-HCCs. Conspicuity scores on the Kupffer phase were significantly higher than those on B-US for both HCCs (2.87±0.85 vs. 1.79±0.71) and non-HCCs (3.06±0.79 vs. 2.00±0.75) (both P<0.001). The technical success rate of RFA under Kupffer phase guidance was 97.7%. Tumor conspicuity on the Kupffer phase showed a moderate correlation with that on HBP (r=0.436, P<0.001), and this correlation was stronger in non-HCCs (r=0.630, P<0.001). Multivariable analysis identified B-US hypoechogenicity (odds ratio [OR], 1.424; 95% confidence interval [CI], 1.176 to 1.724; P<0.001) and good HBP conspicuity (OR, 1.317; 95% CI, 1.087 to 1.596; P=0.005) as independent predictors of good Kupffer phase conspicuity. Conclusion B-US hypoechogenicity and good HBP conspicuity are independent predictors of favorable tumor conspicuity on the Kupffer phase. Identifying these features may facilitate optimal patient selection for effective SZUS-guided RFA of tumors that are inconspicuous on B-US.
Purpose: Limited access to specialist expertise in point-of-care ultrasound (POCUS) in rural areas may adversely affect patient care and healthcare systems by increasing reliance on costly imaging modalities (e.g., computed tomography or magnetic resonance imaging [MRI] and unnecessary patient transfers to specialized centers. Telemedical support represents a promising strategy to address this gap. Methods: In this block-randomized controlled trial with allocation concealment, a total of 358 patients requiring ultrasound were assigned to two POCUS groups: 184 patients received standard POCUS without teleconsultation, and 174 received POCUS supported by remote experts via telemedicine. All examinations were performed by the most experienced available local providers. Standardized post-examination questionnaires were administered to assess perceptions of the diagnostic process. Results: No statistically significant differences were observed between telemedicine-assisted POCUS and standard POCUS. The study also provides insights into the feasibility and diagnostic performance of teleconsultation-supported ultrasound in real-world clinical settings. MRI utilization was significantly lower in the teleconsultation group (P=0.002). Conclusion: Telemedicine-assisted POCUS demonstrated acceptability and comparable care outcomes relative to standard practice. Its potential to reduce reliance on high-cost diagnostic modalities supports its relevance as a scalable and efficient care model.
Purpose This study aimed to investigate whether, and by what mechanisms, focused ultrasound–mediated mechanical stimulation (MS) can induce anti-tumor immunity and elicit an abscopal effect in a pancreatic cancer model. Methods In study 1, animals bearing unilateral murine pancreatic tumors (Pan02) in the flank were divided into five groups according to the single or combined use of gemcitabine (Gem), thermal ablation, or MS. Study 2 was conducted in mice bearing bilateral flank tumors to evaluate abscopal effects. Tumor growth suppression, tissue damage, expression of tumor growth-inhibitory genes and cytokines, and anti-tumor cytotoxic T lymphocyte responses were analyzed. Results In study 1, the MS+Gem group exhibited significantly higher levels of interleukin-6, KC-GRO, and tumor necrosis factor-α; higher proportions of CD8+ cells and granzyme B (GrB); and lower Foxp3 expression than the other groups. A significantly higher ratio of CD8+ cells among tumor-infiltrating lymphocytes (TIL) was also observed in the MS+Gem group (P<0.005 at week 2). In study 2, significant growth suppression of the untreated contralateral tumor was observed in the MS+Gem group. Immune analysis of the untreated tumor showed significantly higher proportions of CD8+ cells and GrB, along with a lower proportion of Foxp3+ cells, in the MS+Gem group. The MS+Gem group also demonstrated a higher CD8+/TIL ratio in the untreated tumor. Conclusion MS+Gem effectively suppressed tumor growth, promoted apoptosis-related factors, and enhanced intratumoral infiltration of cytotoxic T cells in treated tumors. In addition, MS+Gem induced an abscopal effect in untreated tumors, suggesting its potential to mediate systemic anti-tumor immune responses in pancreatic cancer treatment.