α-Glucosidase inhibitors boost gut immunity by inducing IgA responses in Peyer's patches.

Peyer's patches (PPs) are specialized gut-associated lymphoid tissues that initiate follicular helper T (Tfh)-mediated immunoglobulin A (IgA) response to luminal antigens derived from commensal symbionts, pathobionts, and dietary sources. IgA-producing B cells migrate from PPs to the small intestinal lamina propria and secrete IgA across the epithelium, modulating the ecological balance of the commensal microbiota and neutralizing pathogenic microorganisms. α-glucosidase inhibitors (α-GIs) are antidiabetic drugs that inhibit carbohydrate digestion in the small intestinal epithelium, leading to alterations in the commensal microbiota composition and metabolic activity. The commensal microbiota and IgA responses exhibit bidirectional interactions that modulate intestinal homeostasis and immunity. However, the effect of α-GIs on the intestinal IgA response remains unclear. We investigated whether α-GIs affect IgA responses by administering voglibose and acarbose to mice via drinking water. We analyzed Tfh cells, germinal center (GC) B cells, and IgA-producing B cells in PPs by flow cytometry. We also assessed pathogen-specific IgA responses. We discovered that voglibose and acarbose induced Tfh cells, GCB cells, and IgA-producing B cells in the PPs of the proximal small intestine in mice. This effect was attributed to the modification of the microbiota rather than a shortage of monosaccharides. Furthermore, voglibose enhanced secretory IgA (S-IgA) production against attenuated Salmonella Typhimurium. Our findings reveal a novel mechanism by which α-GIs augment antigen-specific IgA responses by stimulating Tfh-GCB responses in PPs, and suggest a potential therapeutic application as an adjuvant for augmenting mucosal vaccines.

Value of Dual-Energy Computed Tomography for Detecting Small Pancreatic Ductal Adenocarcinoma.

OBJECTIVE: The aim of the study is to evaluate the usefulness of virtual monoenergetic imaging (VMI) generated from dual-energy computed tomography (DECT) in detecting small pancreatic ductal adenocarcinomas (PDACs). METHODS: This study included 82 patients pathologically diagnosed with small PDAC (≤30 mm) and 20 without pancreatic tumors who underwent triple-phase contrast-enhanced DECT. To assess diagnostic performance for small PDAC detection via a receiver operating characteristic analysis, 3 observers reviewed 2 image sets (conventional computed tomography [CT] set and combined image set [conventional CT + 40-keV VMI from DECT]). The tumor-to-pancreas contrast-to-noise ratio was compared between conventional CT and 40-keV VMI from DECT. RESULTS: The area under the receiver operating characteristic curve of the 3 observers were 0.97, 0.96, and 0.97 in conventional CT set and 0.99, 0.99, and 0.99 in combined image set (P = 0.017-0.028), respectively. The combined image set yielded a better sensitivity than the conventional CT set (P = 0.001-0.023), without a loss of specificity (all P > 0.999). The tumor-to-pancreas contrast-to-noise ratios of 40-keV VMI from DECT were approximately threefold higher than those of conventional CT at all phases. CONCLUSIONS: The addition of 40-keV VMI from DECT to conventional CT had better sensitivity for detecting small PDACs without compromising specificity.

Extracellular volume fraction with MRI: As an alternative predictive biomarker to dynamic contrast-enhanced MRI for chemotherapy response of pancreatic ductal adenocarcinoma.

PURPOSE: To assess the feasibility of extracellular volume (ECV) fraction determined with equilibrium contrast-enhanced MRI for prediction of treatment response to chemotherapy in pancreatic ductal adenocarcinoma (PDAC) in comparison with dynamic contrast-enhanced MRI (DCE-MRI), and to clarify the association between ECV fraction and DCE-MRI-derived pharmacokinetic parameters. METHODS: This retrospective study included 58 consecutive patients with histologically confirmed PDAC who underwent DCE-MRI before systemic chemotherapy. Tumor pharmacokinetic parameters, including the volume transfer coefficient (Ktrans), rate constant (kep), and extracellular extravascular volume fraction (ve) of DCE-MRI, and ECV fraction determined with equilibrium contrast-enhanced MRI were compared between the response and non-response groups. The correlation of tumor ECV fraction with each DCE-MRI-derived pharmacokinetic parameter was examined using Spearman's rank correlation coefficient. RESULTS: Tumor Ktrans, ve, and ECV fraction were significantly higher in the response group than in the non-response group (all, P < 0.001), whereas no significant difference was found in kep (P = 0.119). Tumor ECV fraction showed the highest area under receiver operating characteristic curve of 0.918, with a sensitivity of 89.3%, specificity of 90.0%, and accuracy of 89.7% (cut off, >37.6%). The ECV fraction showed a significant positive correlation with Ktrans (Spearman's coefficient = 0.66, P < 0.001) and ve (Spearman's coefficient = 0.79, P < 0.001). CONCLUSIONS: ECV fraction determined with equilibrium contrast-enhanced MRI was as useful as DCE-MRI-derived pharmacokinetic parameters for predicting treatment response to chemotherapy in patients with PDAC.

Adding Delayed Phase Images to Dual-Phase Contrast-Enhanced CT Increases Sensitivity for Small Pancreatic Ductal Adenocarcinoma.

BACKGROUND. Contrast-enhanced CT performed for pancreatic ductal adeno-carcinoma (PDAC) detection traditionally uses a dual-phase (pancreatic and portal venous) protocol. However, PDAC may exhibit isoattenuation in these phases, hindering detection. OBJECTIVE. The purpose of this study was to assess the impact on diagnostic performance in detection of small PDAC when a delayed phase is added to dual-phase contrast-enhanced CT. METHODS. A database of 571 patients who underwent triple-phase (pancreatic, portal venous, and delayed) contrast-enhanced MDCT between January 2017 and March 2020 for suspected pancreatic tumor was retrospectively reviewed. A total of 97 patients had pathologically confirmed small PDAC (mean size, 22 mm; range, 7-30 mm). Twenty control patients had no pancreatic tumor suspected on CT, on initial MRI and follow-up CT, or on MRI after 12 months or longer. Three radiologists independently reviewed dual-phase and triple-phase images. Two additional radiologists assessed tumors' visual attenuation on each phase, reaching consensus for differences. Performance of dual- and triple-phase images were compared using ROC analysis, McNemar test, and Fisher exact test. RESULTS. AUC was higher (p < .05) for triple-phase than dual-phase images for all observers (observer 1, 0.97 vs 0.94; observer 2, 0.97 vs 0.94; observer 3, 0.97 vs 0.95). Sensitivity was higher (p < .001) for triple-phase than dual-phase images for all observers (observer 1, 74.2% [72/97] vs 59.8% [58/97]; observer 2, 88.7% [86/97] vs 71.1% [69/97]; observer 3, 86.6% [84/97] vs 72.2% [70/97]). Specificity, PPV, and NPV did not differ between image sets for any reader (p ≥ .05). Seventeen tumors showed pancreatic phase visual isoattenuation, of which nine showed isoattenuation and eight hyperattenuation in the delayed phase. Of these 17 tumors, 16 were not detected by any observer on dual-phase images; of these 16, six were detected by at least two observers and five by at least one observer on triple-phase images. Visual attenuation showed excellent interob-server agreement (κ = 0.89-0.96). CONCLUSION. Addition of a delayed phase to pancreatic and portal venous phase CT increases sensitivity for small PDAC without loss of specificity, partly related to delayed phase hyperattenuation of some small PDACs showing pancreatic phase isoattenuation. CLINICAL IMPACT. Addition of a delayed phase may facilitate earlier PDAC detection and thus improved prognosis.