廣岡 芳樹

Background and Aims: Crohn’s disease (CD) is a chronic inflammatory bowel disease characterized by gastrointestinal inflammation, with gut microbiota dysbiosis playing a key role in its onset and progression. This study aimed to evaluate whether 1-kestose supplementation modulates gut microbiota composition and mucin degradation–related biomarkers in patients with clinically inactive to mild CD, and to explore plausible ecological mechanisms in vitro. Study Design: Single-arm pilot intervention study with exploratory laboratory experiments. Place and Duration of Study: Samples were collected at Tokai University Hospital (Japan), and microbiome/qPCR analyses and in vitro assays were performed at Fujita Health University (Japan). The supplementation period was four months. Methodology: Nineteen patients with clinically inactive to mild CD (CDAI ≤ 220) received 1-kestose (3 g) twice daily for 4 months. Fecal microbiota composition was assessed by 16S rRNA gene sequencing, and qPCR quantified nanA homologs (nan levels) as a functional marker related to mucin-degrading potential. Clinical biomarkers (CDAI, fecal calprotectin, CRP, albumin) were monitored. To investigate potential mechanisms, in vitro cultures of Ruminococcus gnavus and Bifidobacterium longum were performed under sugar-supplemented conditions, including 1-kestose, and growth responses were evaluated; short-chain fatty acids (SCFAs) were descriptively assessed in pooled culture supernatants. Results: Clinical biomarkers remained stable throughout supplementation. 1-kestose intake was associated with an increased relative abundance of Bifidobacterium and a decreased abundance of Blautia, along with reduced fecal nan levels. In vitro, B. longum showed enhanced early growth with 1-kestose compared with other sugars, whereas R. gnavus exhibited impaired growth under acidic conditions. Exploratory SCFA measurements suggested higher acetate in sugar-supplemented B. longum cultures. Conclusion: In this single-arm pilot cohort of patients with clinically inactive to mild CD, 1-kestose supplementation was associated with shifts toward potentially beneficial taxa and a reduction in nan levels, a functional marker linked to mucin-degrading potential. These findings, supported by exploratory in vitro observations, suggest that 1-kestose may modulate gut ecological conditions; however, clinical efficacy and causality require confirmation in randomized, placebo-controlled trials with detailed dietary and medication monitoring.

BACKGROUND/AIM: Atezolizumab plus bevacizumab (Ate+Bev) is widely used as first-line therapy for unresectable hepatocellular carcinoma (HCC). However, a subset of patients experience early disease progression, often detected at the first radiologic assessment around 6 weeks. Evidence guiding second-line therapy in this subgroup is limited, and the clinical value of lenvatinib after early progressive disease (PD) remains unclear. PATIENTS AND METHODS: We retrospectively analyzed 36 patients with unresectable HCC who received lenvatinib after failure of first-line Ate+Bev. Patients were stratified by early PD, defined as radiologic progression at the scheduled 6-week assessment after starting Ate+Bev. Outcomes included antitumor response, progression-free survival (PFS), and overall survival (OS). RESULTS: Objective response rate (ORR) and disease control rate (DCR) assessed by RECIST 1.1 were comparable between patients with and without early PD (ORR: 28.6% vs. 13.8%; DCR: 85.7% vs. 86.2%; p=0.342). Median PFS was also similar between groups [5.2 months (95% confidence interval=1.9-NA) vs. 6.1 months (3.7-7.5); p=0.307]. In multivariate analyses adjusting for Child-Pugh class, Barcelona Clinic Liver Cancer (BCLC) stage, and reduced starting dose, early PD was not significantly associated with either PFS or OS, whereas Child-Pugh class A was independently associated with improved OS. Correlation between first- and second-line PFS was weak and non-significant (r=0.077, p=0.682). CONCLUSION: Lenvatinib demonstrated comparable antitumor activity and survival outcomes even in patients with early PD on first-line Ate+Bev, indicating that early radiologic progression does not necessarily signify refractoriness to subsequent systemic therapy. These findings support lenvatinib as a viable second-line option regardless of early Ate+Bev response, particularly in patients with preserved liver function. Larger prospective studies are needed to confirm these observations.

Aims: To characterize fecal gut microbiota features associated with a history of aggression in dogs and to explore whether supplementation with the prebiotic fructooligosaccharide 1-kestose is associated with alterations in gut microbiota composition and owner-reported aggression-related behaviors. Study Design: An exploratory, non-randomized field study comparing aggressive and non-aggressive client-owned dogs, followed by a single-arm pre–post supplementation study in aggressive dogs with owner-reported behavioral outcomes. Place and Duration of Study: The study was conducted in Japan between 2021 and 2023, with a 60-day 1-kestose supplementation period for the intervention group. Methodology: Fecal samples from aggressive toy poodles (Agg; n = 10) and non-aggressive controls (N-Agg; n = 6) were analyzed using 16S rRNA gene sequencing. Dogs in the Agg group received 1-kestose (400 mg/day) for 60 days. Behavioral outcomes were assessed before and after supplementation using the shortened, owner-reported Canine Behavioral Assessment and Research Questionnaire (C-BARQ). Genome analysis of Blautia caecimuris was conducted to identify glycoside hydrolase family 32 (GH32) enzymes, and a recombinant GH32 enzyme was functionally characterized for fructooligosaccharide hydrolysis. Results: At baseline, Agg dogs differed in gut microbial β-diversity from N-Agg dogs and showed higher relative abundances of Mediterraneibacter gnavus, the Segatella copri group, and the Phocaeicola vulgatus group. Following 1-kestose supplementation, M. gnavus was lower, the B. caecimuris group was higher, and the β-diversity difference between groups diminished. In parallel, owner-reported aggression-related C-BARQ items—particularly responses to unfamiliar dogs and strangers near the home—were lower after supplementation. The characterized GH32 enzyme from B. caecimuris hydrolyzed 1-kestose and nystose. Conclusion: These findings indicate that 1-kestose supplementation is associated with concurrent alterations in the canine gut microbiota and owner-reported aggression-related behavioral scores. While causality cannot be established, the results support further investigation of microbiota–behavior associations using larger, well-controlled study designs incorporating objective physiological and microbial measurements.

AIM: This study evaluated the relationship between longitudinal dosing patterns and clinical outcomes of cabozantinib used as third- or later-line therapy in advanced hepatocellular carcinoma (HCC) previously treated with immune checkpoint inhibitors (ICIs), focusing on disease control (DC). METHODS: We retrospectively analyzed 33 patients with unresectable HCC who had received atezolizumab plus bevacizumab and lenvatinib, followed by cabozantinib. Tumor response was assessed by Response Evaluation Criteria in Solid Tumors v1.1, and patients were classified into DC (complete response/partial response/stable disease) or non-DC (progressive disease/not evaluable) groups. Initial dose, longitudinal dosing, and treatment outcomes were compared. RESULTS: Most patients (90.9%) started at reduced doses (40 mg/day: n = 18; 20 mg/day: n = 12), with only three starting at 60 mg/day. Objective response rate was 3.0%, and DC rate was 51.5%. Compared with the non-DC group, the DC group had significantly longer median progression-free survival (4.4 vs. 1.2 months; p < 0.0001), overall survival (10.7 vs. 3.0 months; p = 0.0456), and treatment duration (134 vs. 22 days; p < 0.0001). Time to first dose reduction and average daily dose over the first 6 weeks did not differ significantly between groups. Child-Pugh class A was independently associated with DC and survival. CONCLUSIONS: In real-world practice, cabozantinib is often initiated at reduced doses, yet DC can be achieved even at ∼20 mg/day. For patients with preserved liver function, long-term stable disease is attainable, and individualized dose-reduction strategies represent an effective and feasible approach in later-line HCC treatment after ICIs.

ABSTRACT Psychiatric disorders such as major depressive disorder are closely linked to the intestinal environment, suggesting intestinal health may contribute to their prevention. Prebiotics, which enhance intestinal health, are promising candidates for preventing psychiatric disorders. 1‐Kestose (kestose), a type of prebiotics, has shown potential, but its effects on psychiatric disorders remain unclear. In this study, we investigated whether kestose prevents abnormal behaviors induced by social isolation (SI) stress and which underlies mechanisms of preventive effects. C57BL/6J male mice (3 weeks old) were divided into two groups: individually housed (SI) group and housed five mice per cage (GH) group. Each group received either a normal diet or a kestose diet (5% kestose) for 5 weeks daily until the end of the behavioral testing. Kestose prevented the SI‐induced abnormal behaviors including reduced sociality, impaired spatial recognition, and heightened anxiety, which were associated with suppressed microglial activation in the hippocampus. Kestose altered the diversity of gut microbiota and increased the abundance of Bacteroides sartorii . Furthermore, short‐chain fatty acids (SCFAs) such as butyric acid, acetic acid, and propionic acid, produced by intestinal microbiota, were increased after kestose supplementation. Positive correlations were observed between B. sartorii abundance and SCFA levels, suggesting that B. sartorii contributes to SCFA production. Notably, both B. sartorii and SCFAs were strongly associated with the abnormal behaviors by SI. These findings suggest that kestose prevents SI‐induced abnormal behaviors by modulating gut microbiota, particularly B. sartorii , through an increase of SCFA production. Taken together, kestose could be used as a promising prebiotic intervention for psychiatric disorders. image

Shear wave elastography provides quantitative data on tissue stiffness, but was not available for endoscopic ultrasound until recently. The present study investigated the utility of a newly developed endoscopic ultrasound-guided shear wave measurement for diagnosing upper gastrointestinal subepithelial lesions. Shear wave velocity (Vs) was measured as an indicator of tissue stiffness, and the total amount of effective shear waves (VsN) was used as a reliability index for Vs values obtained by endoscopic ultrasound-guided shear wave measurements. Among the Vs values obtained, the five with the highest VsN were selected, and their median was defined as the median Vs (Vs-med). The median VsN of the five Vs values was defined as the median VsN (VsN-med). Endoscopic ultrasound-guided shear wave measurements were performed on 23 patients, with no complications occurring in any procedure. Histopathological diagnoses included 12 gastrointestinal stromal tumors, seven leiomyomas, and four schwannomas. Vs-med values for gastrointestinal stromal tumors, leiomyomas, and schwannomas were 2.46, 1.73, and 2.85 m/s, respectively, indicating that gastrointestinal stromal tumors and schwannomas were significantly stiffer than leiomyomas. VsN-med values for gastrointestinal stromal tumors, leiomyomas, and schwannomas were 40.5, 39, and 35.5%, respectively, with no significant differences. Endoscopic ultrasound-guided shear wave measurements are feasible for upper gastrointestinal subepithelial lesions and allow for the objective, non-invasive quantification of lesion stiffness. These results suggest the potential of endoscopic ultrasound-guided shear wave measurements as a valuable tool for the differential diagnosis of upper gastrointestinal subepithelial lesions.

BACKGROUND: Cancer gene panel testing (CGP) helps comprehensively analyze a large number of genes, extracting genetic information from the genome profile to aid treatment plans and drug therapy. Advances in drug therapy and surgical treatment for intrahepatic cholangiocarcinoma (ICC) have improved patient outcomes; however, it remains a typical intractable cancer with a poor prognosis. ICC is one of the key tumors for which effective treatment may be identified through CGP testing. This study aimed to identify ICC harboring actionable genetic variants using contrast-enhanced ultrasonography (CE-US). METHODS: We enrolled 26 ICC patients who underwent CE-US before chemotherapy or surgery. Three ultrasound specialists reviewed the images by consensus and assessed the imaging features, including vascularity. Pathological data were reviewed after diagnosis using CE-US. We retrospectively analyzed distinctive CE-US findings in patients with ICC with actionable genetic variants. RESULTS: Twelve ICC patients had actionable gene variants, including four FGFR2 fusions, one FGFR2 rearrangement, six IDH1 mutations, and one BRAF V600E mutation. Univariate analysis showed significant differences in bile duct invasion (p = 0.0217) and blood vessel penetration within the tumor (p = 0.0012). Multivariable logistic regression identified blood vessel penetration within the tumor (OR = 18.275; 95% CI: 1.331-250.925; p = 0.0297) as independently associated with actionable gene variants. CONCLUSION: Patients with ICC and blood vessel penetration on CE-US should be considered for CGP testing.

INTRODUCTION: Gastrectomy considerably affects the gut microbiome; however, the association between dysbiosis and post-gastrectomy syndrome remains to be explored. This study prospectively explored fecal gut microbiota alterations before and 3 months after gastrectomy, investigating their potential association with weight loss. METHODS: The gut microbiome of 21 patients with gastric cancer scheduled for gastrectomy in April-October 2022 was analyzed using 16S rRNA gene Next-Generation Sequencing. Their microbiome profiles were compared to those of healthy controls. Bacterial taxa demonstrating significant changes were determined using the Linear Discriminant Analysis Effect Size algorithm and further analyzed for their relationship with weight loss in the gastrectomy cohort. RESULTS: Postoperative complications (≥grade 2) were observed in 14.3% of patients. Postoperative weight loss was －10.9%, with the following breakdown: distal (－7.0%), total (－13.5%), and proximal (－14.0%) gastrectomy (P = 0.003). Microbiota analysis demonstrated a significant incline in the abundance of the Streptococcus salivarius group and a decline in Bacteroides uniformis in patients with gastric cancer compared to healthy controls. The S. salivarius group exhibited a further increase, while B. uniformis showed signs of recovery after gastrectomy. Additionally, 5α-reductase gene levels, reported to decrease as several cancers progress, were found to elevate post-surgery. Furthermore, patients experiencing greater weight loss showed a significant reduction in Faecalibacterium prausnitzii levels, while lower serum prealbumin and zinc levels were associated with the abundance of Escherichia coli. CONCLUSION: Gastrectomy significantly alters the gut microbiome. Supporting microbiome health with prebiotics may help alleviate postoperative issues and improve patients' quality of life.

Objective In 2021, anamorelin, an orally active ghrelin receptor selective antagonist, was approved for the treatment of cachexia in patients with non-small cell lung cancer, gastric cancer, pancreatic cancer, and colon cancer. Cancer cachexia is classified into three stages: pre-cachexia, cachexia, and refractory cachexia, with the pre-cachexia and cachexia stages considered reversible with a combination of nutritional therapy, pharmacotherapy, and exercise therapy. In addition, treatment of cachexia requires early intervention, but diagnosis and early detection of cachexia are difficult. We hypothesized that the initiation of anamorelin treatment may be delayed in clinical practice and explored the appropriate timing of treatment initiation. Methods The data of patients with cachexia who received anamorelin at our hospital from June 2021 to July 2023 were retrospectively reviewed. Anamorelin was administered to 201 patients, of whom 134 were included in the study. Survival time and duration of medication were compared based on the number of objective criteria for anamorelin prescription (C-reactive protein [CRP] >0.5 mg/dL, hemoglobin <12 g/dL, albumin <3.2 g/dL). Multivariate analysis was used to determine the factors associated with continuation of anamorelin treatment for 12 weeks. Results Patients with a higher number of objective criteria for anamorelin prescription (CRP >0.5 mg/dL, hemoglobin <12 g/dL, albumin <3.2 g/dL) had shorter anamorelin treatment duration and survival. In multivariate analysis, 12 weeks of anamorelin treatment was associated with CRP. Comparing CRP ≤0.5 mg/dL vs. CRP >0.5 mg/dL, survival was significantly longer for CRP ≤0.5 mg/dL (p < 0.01). Conclusions Initiating anamorelin treatment with close attention to CRP and ensuring that prescribing criteria are met may be helpful in treating cachexia.

The new Kyoto guidelines for the management of intraductal papillary mucinous neoplasm (IPMN) provide evidence-based recommendations for the diagnosis and treatment of IPMN. Endoscopic ultrasonography (EUS) is a diagnostic modality with a high spatial resolution that allows detailed observation and obtaining cyst fluid or tissue samples via EUS-guided fine needle aspiration (EUS-FNA). Currently, EUS is an indispensable examination method for the diagnosis of pancreatic diseases. On the other hand, there have been concerns that EUS imaging tends to be highly operator-dependent, and may lack objectivity. Previous guidelines have assigned EUS as an option for patients with worrisome features. However, recent reports indicate that the sensitivity of EUS for the diagnosis of mural nodules (MNs) is more than 90%, comparable or superior to that of contrast-enhanced computed tomography or magnetic resonance cholangiopancreatography. The specific advantages of EUS in the diagnosis of IPMN are: (1) high spatial resolution imaging for the diagnosis of MNs, (2) contrast-enhanced EUS for differentiation of intra-cystic MNs from mucous clots, and (3) pathological diagnosis using EUS-FNA and differential diagnosis of a pancreatic cystic tumor by cystic fluid analysis. In order to utilize EUS in the diagnosis of IPMN, endoscopists are required to have the skills to provide sufficiently objective imaging findings.

PURPOSE: This study aimed to clarify the current treatment status for biliary tract cancers based on data from the National Clinical Database (NCD) in Japan. METHODS: Total 3895 cases of biliary tract cancers registered in the NCD during 2021 were included. We identified the rates of resection, R0 resection, postoperative complications, and incidences of lymph node metastasis for gallbladder carcinoma, perihilar cholangiocarcinoma, distal bile duct carcinoma, and ampullary carcinoma. RESULTS: The number of biliary tract cancers registered in the NCD during 2021 was 3895 (1775 in extrahepatic bile duct carcinoma, 1422 in gallbladder carcinoma, and 698 in ampullary carcinoma). In gallbladder carcinoma, the resection (89.59%) and R0 resection rates (87.99%) were favorable, and the complication rate (6.05%) was lower than that of others. However, the postoperative complication rate could be higher in T3-T4 cases and when extrahepatic bile duct resection was performed concomitantly. Lymph node metastasis was frequently seen in 12.60% at the No. 13a lymph node. In perihilar cholangiocarcinoma, the R0 resection (69.82%) and complication rates (16.75%) were significantly lower and higher, respectively. In distal cholangiocarcinoma and ampullary carcinoma, metastasis was observed in approximately 2% and 10% of the dissected No. 16b1 para-aortic lymph nodes, respectively. In conclusion, although short-term surgical outcomes for biliary tract cancers in Japan might be acceptable, the significantly lower R0 resection and higher complication rates of perihilar cholangiocarcinomas indicate additional challenges for surgeons in the future and should continue to be monitored by the Japanese Society of Hepatobiliary and Pancreatic Surgery.

Feline atopic skin syndrome (FASS) is a chronic inflammatory skin disease characterized by itching and dermatitis. While the relationship between the gut microbiota and atopic dermatitis (AD) has been highlighted, exploring gut-targeted therapies for FASS remain limited. This study aimed to evaluate the effects of a parasynbiotic containing 1-kestose and heat-killed Lactobacillus plantarum FM8 on clinical symptoms and gut microbiota in cats with FASS. Eleven FASS cats were treated with a parasynbiotic containing 1-kestose (400 mg/day) and heat-killed FM8 (2.0 × 1010 CFU/day) for 8 weeks. Clinical symptoms were assessed using the SCORing Feline Allergic Dermatitis (SCORFAD), investigator pruritus score (IPS), and rating of global assessment of improvement (GAI). Fecal microbiota composition was analyzed through 16S rRNA sequencing, with 16 healthy cats serving as controls. Parasynbiotic intervention significantly reduced SCORFAD and IPS scores. GAI scores improved in 10 of 11 cats, with the most severe case maintaining a score of 3. The β-diversity analysis showed no significant differences; however, a trend toward variation was observed between the healthy control cats and the baseline group of FASS cats, as well as between the healthy control cats and post- intervention groups. The abundance of Collinsella stercoris was significantly higher in FASS cats than in healthy controls, and it significantly decreased after parasynbiotic intervention, suggesting potential improvements in gut health and inflammation. This study is the first to demonstrate the potential benefits of parasynbiotic administration in FASS, showing improvements in clinical symptoms and partial modulation of the gut microbiota. These findings highlight parasynbiotic administration as a compelling therapeutic approach for FASS, offering new possibilities for innovative interventions aimed at the gut–skin axis.

Recent studies have linked Ruminococcus gnavus to inflammatory bowel disease and Fusobacterium nucleatum to various cancers. Agarooligosaccharides (AOS), derived from the acid hydrolysis of agar, have shown significant inhibitory effects on the growth of R. gnavus and F. nucleatum at concentrations of 0.1 and 0.2%, respectively. RNA sequencing and quantitative reverse-transcription PCR analyses revealed the downregulation of fatty acid biosynthesis genes (fab genes) in these bacteria when exposed to 0.1% AOS. Furthermore, AOS treatment altered the fatty acid composition of R. gnavus cell membranes, increasing medium-chain saturated fatty acids (C8, C10) and C18 fatty acids while reducing long-chain fatty acids (C14, C16). In contrast, no significant growth inhibition was observed in several strains of Bifidobacteria and Lactobacillales at AOS concentrations of 0.2 and 2%, respectively. Co-culture experiments with R. gnavus and Bifidobacterium longum in 0.2% AOS resulted in B. longum dominating the population, constituting over 96% post-incubation. In vivo studies using mice demonstrated a significant reduction in the Lachnospiraceae family, to which R. gnavus belongs, following AOS administration. Quantitative PCR also showed lower levels of the nan gene, potentially associated with immune disorders, in the AOS group. These findings suggest that AOS may introduce a novel concept in prebiotics by selectively inhibiting potentially pathogenic bacteria while preserving beneficial bacteria such as Bifidobacteria and Lactobacillales.

Aim: This study aimed to establish a non-invasive, rapid, and cost-effective method to assess the potential risk of immune and psychiatric disorders by quantifying nan gene levels in gut microbiota, specifically focusing on Ruminococcus gnavus and other Lachnospiraceae species associated with mucin degradation. Methodology: We first designed a primer set targeting the consensus sequence of the nanA gene, which is highly conserved within nan gene clusters. To validate this primer set, we performed Next-Generation Sequencing (NGS) on the PCR-amplified fragments. To explore the association between nan levels and immune or psychiatric disorders, we conducted qPCR to quantify nan levels in the intestines, analyzing intestinal DNA from both allergy-induced mice with or without fructan treatment, and dogs with or without aggressive behavior. Additionally, to assess whether nan levels reflect the clinical status of immune disorders, fecal samples were collected from 45 patients with ulcerative colitis (UC) and analyzed for nan levels. Results: NGS analysis of DNA fragments amplified from various intestinal samples using the nan primer set confirmed the presence of nanA sequences from R. gnavus and other members of the Lachnospiraceae family, including Blautia and Dorea species. The qPCR quantification of nan levels using this primer set revealed that allergy-induced mice treated with fructans, which are known to be associated with lower allergy scores compared to untreated mice, exhibited significantly reduced nan levels. Additionally, the nan levels of aggressive dogs were substantially higher than those of non-aggressive dogs. Notably, nan levels were also substantially elevated in patients with UC in comparison to the healthy control individuals. Conclusion: qPCR-based measurement of nan levels in gut microbiota shows potential for selectively detecting pathogenic nan-harboring strains and may reflect the clinical status of immune and psychiatric disorders. This approach could provide a non-invasive, rapid, and cost-effective method for assessing the risk of these disorders.

AIM: To investigate the characteristics and prognosis of patients with advanced hepatocellular carcinoma (HCC) treated with atezolizumab and bevacizumab (Atz/Bev) who achieved a complete response (CR) according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). METHODS: A total of 120 patients with Eastern Cooperative Oncology Group performance status (PS) 0 or 1 and Child-Pugh A at the start of Atz/Bev treatment were included. Barcelona Clinic Liver Cancer stage C was recorded in 59 patients. RESULTS: The CR rate with Atz/Bev alone was 15.0%. The median time to CR was 3.4 months, and the median duration of CR was 15.6 months. A significant factor associated with achieving CR with Atz/Bev alone was an AFP ratio of 0.34 or less at 3 weeks. Adding transarterial chemoembolization (TACE) in the six patients who achieved a partial response increased the overall CR rate to 20%. Among the 24 patients who achieved CR, the median progression-free survival was 19.3 months, the median overall survival was not reached, and 14 patients (58.3%) were able to discontinue Atz/Bev and achieve a drug-free status. Twelve of these patients developed progressive disease (PD), but eleven successfully received post-PD treatments and responded well. CONCLUSIONS: Achieving CR by mRECIST using Atz/Bev alone or with additional TACE can be expected to offer an extremely favorable prognosis.

Introduction. Hepatocellular carcinoma (HCC) is one of the deadliest cancers worldwide.Gap statement. Monitoring of HCC and predicting its immunotherapy responses are challenging.Aim. This study explored the potential of the gut microbiome for HCC monitoring and predicting HCC immunotherapy responses.Methods. DNA samples were collected from the faeces of 22 patients with HCC treated with atezolizumab/bevacizumab (Atz/Bev) and 85 healthy controls. The gut microbiome was analysed using 16S rRNA next-generation sequencing and quantitative PCR (qPCR).Results. The microbiomes of patients with HCC demonstrated significant enrichment of Lactobacillus, particularly Lactobacillus fermentum, and Streptococcus, notably Streptococcus anginosus. Comparative analysis between Atz/Bev responders (R) and non-responders (NR) revealed a higher abundance of Bacteroides stercoris in the NR group and Bacteroides coprocola in the R group. Using qPCR analysis, we observed elevated levels of S. anginosus and reduced levels of 5α-reductase genes, essential for the synthesis of isoallolithocholic acid, in HCC patients compared to controls. Additionally, the analysis confirmed a significantly lower abundance of B. stercoris in the Atz/Bev R group relative to the NR group.Conclusions. The gut microbiome analysis and specific gene quantification via qPCR could provide a rapid, less invasive, and cost-effective approach for assessing the increased risk of HCC, monitoring patient status, and predicting immunotherapy responses.

Less than half of all patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) respond to chemotherapy, and the prognosis of PDAC is poor, which may be mediated by the gut microbiota. We investigated the clinical improvement effects of 1-kestose, a fructooligosaccharide, on PDAC chemotherapy in this single-center, randomized, controlled pilot trial conducted at Fujita Health University Hospital, which enrolled patients with PDAC. The trial included 1-kestose administration and non-administration groups. The 1-kestose group received 9 g of 1-kestose daily for 12 weeks, and their blood markers, imaging studies, physical findings, and gut microbiota were evaluated. In the 1-kestose administration group, the cancer marker CA19-9 significantly decreased, and there was a reduction in the neutrophil-to-lymphocyte ratio (NLR). There was also suppression of the reduction of albumin levels and of an increase in C-reactive protein. Additionally, Escherichia coli, which typically increases in PDAC, significantly decreased in the 1-kestose group. Thus, 1-kestose altered the gut microbiota and improved the prognostic factors for PDAC. Large-scale, long-term trials of 1-kestose interventions for PDAC are thus warranted to improve the prognosis of PDAC.

BACKGROUND: Patients with isolated IgG4-related sclerosing cholangitis (IgG4-SC) often undergo unnecessary resection. The aim of this study was to validate the revised Japanese diagnostic criteria for isolated IgG-4-SC and to improve awareness about this condition in the population. METHODS: This was a Japanese retrospective multicenter study. We focused on the data and diagnostic yield obtained using the Japanese diagnostic criteria published initially in 2012 and revised later in 2020 for the diagnosis of isolated IgG4-SC. RESULTS: Patients with isolated IgG4-SC could be classified into two groups based on the primary location of the lesion: the hilar type (n = 40) and the extrahepatic type (n = 13). In total, 10 patients with the hilar type had undergone unnecessary resection. The revised 2020 criteria are useful for the diagnosis of extrahepatic lesions, which are not included in the 2012 criteria. The need for a steroid trial was reduced from 37.7% when the diagnosis was based on the 2012 criteria to 7.6% when the diagnosis was based on the revised 2020 criteria. The diagnostic specificity also improved from 58.5% for the 2012 criteria to 88.7% for the revised 2020 criteria. CONCLUSION: Our validation of the 2020 criteria for the diagnosis of IgG4-SC could contribute to avoiding unnecessary resection in patients with isolated IgG4-SC, which can be classified into the hilar and extrahepatic types. The 2020 criteria can enhance the diagnosis rate of isolated IgG4-SC and uncover this tough-to-diagnose entity based on inclusion of the imaging findings and decrease the dependence on a steroid trial.

The relationship between antitumor response and tumor marker changes was evaluated in patients with advanced hepatocellular carcinoma treated with durvalumab plus tremelimumab (Dur/Tre). Forty patients were enrolled in this retrospective evaluation of treatment outcomes. According to the Response Evaluation Criteria for Solid Tumors version 1.1 at 8 weeks, the objective response (OR) rate was 25% and the disease control (DC) rate was 57.5%. The median alpha-fetoprotein (AFP) ratio at 4 weeks was 0.39 in patients who achieved OR at 8 weeks (8W-OR group), significantly lower than the 1.08 in the non-8W-OR group (p = 0.0068); however, it was 1.22 in patients who did not achieve DC at 8 weeks (non-8W-DC group), significantly higher than the 0.53 in the 8W-DC group (p = 0.0006). Similarly, the median des-γ-carboxy-prothrombin (DCP) ratio at 4 weeks was 0.15 in the 8W-OR group, significantly lower than the 1.46 in the non-8W-OR group (p < 0.0001); however, it was 1.23 in the non-8W-DC group, significantly higher than the 0.49 in the 8W-DC group (p = 0.0215). Early changes in tumor markers after Dur/Tre initiation were associated with antitumor response. In particular, changes in AFP and DCP at 4 weeks may offer useful biomarkers for early prediction of both response and progressive disease following Dur/Tre.