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1.
Dig Dis ; 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39074447

RESUMO

INTRODUCTION: Recently, detection of superficial non-ampullary duodenal epithelial tumors (SNADETs) including adenomas and superficial duodenal carcinomas has increased. Various endoscopic treatment methods have also been reported for SNADETs, but there are few reports on the natural history. The aim of this study was to analyze factors related to tumor growth and determine the characteristics of SNADETs which need early therapeutic intervention. METHODS: A single-center, retrospective study was performed on medical records of 309 patients with SNADETs who underwent endoscopic or surgical resection between January 2010 and May 2021. Of these, 41 patients who were followed up for more than one year by endoscopy were analyzed. The primary outcome was analysis of the tumor growth speed. Secondary outcomes were the relationship between the tumor growth speed and mucin phenotype, tumor size and findings of magnifying endoscopy with narrow-band imaging (M-NBI). RESULTS: The observation period was 24 months (13-182). Tumor growth speed was 1.1 mm/year (0-21.6). Tumor diameter >10 mm at first detection (P=0.004; Odds ratio 19.5(2.03-186.96)) and mixed-type by M-NBI (p=0.036; Odds ratio 9.69(1.05-89.88)) were identified as risk factors of tumors growing at a rate of >3 mm/year. There was no statistically significant difference in the speed of tumor growth between the different mucin immunohistochemical phenotype. CONCLUSION: Initial tumor size and findings of M-NBI are useful to predict tumor growth and consider early intervention.

3.
Nagoya J Med Sci ; 86(2): 280-291, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38962416

RESUMO

Enterovesical fistula (EVF) in Crohn's disease (CD) often does not improve with medical treatment and requires surgical treatment. The surgical treatment strategy for EVF in CD is definitive resection of the intestinal tract side, and performing a leak test using dye injection into the bladder after EVF dissection to determine the appropriate surgical procedure for the bladder side. This study aimed to evaluate the outcomes of surgical treatment for EVF in CD. Twenty-one patients who underwent surgery for EVF between 2006 and 2021 were included and retrospectively evaluated for clinical background, surgical procedures, and postoperative complications. The most common origin of EVF was the ileum (17 cases; 81%), and the most common site of EVF formation was the apex (12; 57%). Surgical approaches were laparotomy in 11 (52%) cases and laparoscopy in 10 (48%). Surgical procedures on the bladder side were fistula dissection in 13 (62%) cases and sutured closure of fistula in 8 (38%). A comparison of approaches revealed no significant difference in operative time, but the amount of blood loss was significantly less in the laparoscopy (p < 0.01). There was no significant difference in the occurrence of postoperative complications between approaches. Postoperative anti-TNF-α antibody agents were used in 17 (81%) cases, and there were no cases of recurrent EVF. In conclusion, definitive resection of the intestinal tract and minimal treatment on the bladder side were sufficient to achieve satisfactory outcomes for EVF in CD.


Assuntos
Doença de Crohn , Fístula Intestinal , Fístula da Bexiga Urinária , Humanos , Doença de Crohn/cirurgia , Doença de Crohn/complicações , Masculino , Feminino , Adulto , Fístula Intestinal/cirurgia , Fístula Intestinal/etiologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Fístula da Bexiga Urinária/cirurgia , Fístula da Bexiga Urinária/etiologia , Resultado do Tratamento , Complicações Pós-Operatórias , Adulto Jovem , Laparoscopia/métodos , Adolescente , Laparotomia/métodos , Laparotomia/efeitos adversos , Idoso
4.
Digestion ; : 1-11, 2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-39033748

RESUMO

INTRODUCTION: Inflammation in ulcerative colitis (UC) originates in the colorectal mucosa. Transcriptome sequencing analysis of the colorectal mucosa allows the identification of potential neuropeptides related to local neurotransmission. The intestinal mucus lining the surface of the mucosa may harbor biomarkers of mucosal inflammation; however, this has not been sufficiently investigated, given the difficulty in obtaining human samples. We previously reported the feasibility of obtaining mucin samples for proteomic analysis by brushing during colonoscopy. Herein, we aimed to investigate the composition of the intestinal mucus and detect neuropeptides characteristic of UC. METHODS: Mucus and mucosal samples were collected from patients with UC from the colorectum in areas showing remission or active UC using a brush catheter and biopsy forceps during colonoscopy. RNA sequencing findings of mucus samples of active and remission areas were compared. RNA and protein expression levels of significantly upregulated neuropeptides were analyzed. RESULTS: Of the neuropeptides associated with UC, somatostatin (SST) was significantly elevated in areas of remission, according to RNA sequencing results of mucus and expression levels in mucus RNA and proteins. Conversely, SST expression in the mucosa was increased in the inflamed areas. Flow cytometry revealed that the fluorescence intensity of SST-positive cells in the remission zone was higher in the mucus than in the mucosa. CONCLUSION: SST expression in the mucus is considered to be an important factor associated with UC activity.

5.
J Gastroenterol ; 59(7): 621-628, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38713262

RESUMO

BACKGROUND: In primary sclerosing cholangitis (PSC), it is important to understand the cholangiographic findings suggestive of malignancy, but it is difficult to determine whether cholangiocarcinoma is present due to modifications caused by inflammation. This study aimed to clarify the appropriate method of pathological specimen collection during endoscopic retrograde cholangiopancreatography for surveillance of PSC. METHODS: A retrospective observational study was performed on 59 patients with PSC. The endpoints were diagnostic performance for benign or malignant on bile cytology and transpapillary bile duct biopsy, cholangiographic findings of biopsied bile ducts, diameters of the strictures and upstream bile ducts, and their differences. RESULTS: The sensitivity (77.8% vs. 14.3%, P = 0.04), specificity (97.8% vs. 83.0%, P = 0.04), and accuracy (94.5% vs. 74.1%, P = 0.007) were all significantly greater for bile duct biopsy than for bile cytology. All patients with cholangiocarcinoma with bile duct stricture presented with dominant stricture (DS). The diameter of the upstream bile ducts (7.1 (4.2-7.2) mm vs. 2.1 (1.2-4.1) mm, P < 0.001) and the diameter differences (6.6 (3.1-7) mm vs. 1.5 (0.2-3.6) mm, P < 0.001) were significantly greater in the cholangiocarcinoma group than in the noncholangiocarcinoma group with DS. For diameter differences, the optimal cutoff value for the diagnosis of benign or malignant was 5.1 mm (area under the curve = 0.972). CONCLUSION: Transpapillary bile duct biopsy should be performed via localized DS with upstream dilation for the detection of cholangiocarcinoma in patients with PSC. Especially when the diameter differences are greater than 5 mm, the development of cholangiocarcinoma should be strongly suspected.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Colangiopancreatografia Retrógrada Endoscópica , Colangite Esclerosante , Manejo de Espécimes , Humanos , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/patologia , Colangite Esclerosante/diagnóstico , Colangite Esclerosante/patologia , Colangite Esclerosante/complicações , Estudos Retrospectivos , Masculino , Feminino , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/diagnóstico , Pessoa de Meia-Idade , Colangiopancreatografia Retrógrada Endoscópica/métodos , Adulto , Idoso , Manejo de Espécimes/métodos , Biópsia/métodos , Sensibilidade e Especificidade , Ductos Biliares Intra-Hepáticos/patologia , Ductos Biliares Intra-Hepáticos/diagnóstico por imagem
6.
Artigo em Inglês | MEDLINE | ID: mdl-38716862

RESUMO

BACKGROUND/PURPOSE: To assess the diagnostic efficacy and safety of endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) using a 19-gauge Franseen needle for autoimmune pancreatitis (AIP). METHODS: Twenty patients suspected of having type 1 AIP were prospectively enrolled and underwent EUS-FNB with a 19-gauge Franseen needle. Their data were compared with those of historical controls: a total of 29 type 1 AIP patients had EUS-FNB with a 22-gauge Franseen needle. RESULTS: Specimens suitable for histological evaluation were obtained from 19 of the 20 patients (95%), and the median total tissue area was 11.9 mm2. The histological diagnosis rate of AIP was 65% (95% CI: 43.2%-82%). Adverse events were observed in three patients (15%), and a switch to 22-gauge needles occurred during transduodenal puncture in two patients. Compared to those punctured with 22-gauge needles, patients punctured with 19-gauge needles had greater prevalence of each characteristic feature of lymphoplasmacytic sclerosing pancreatitis, but the difference was not statistically significant. CONCLUSIONS: EUS-FNB using a 19-gauge Franseen needle demonstrated favorable performance for the histological diagnosis of AIP and allowed for large tissue samples, potentially facilitating pathological diagnosis. However, during transduodenal puncture, maneuverability is reduced; therefore, the needle may need to be selected according to the puncture site.

7.
Cancers (Basel) ; 16(9)2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38730627

RESUMO

The combination of atezolizumab and bevacizumab has become the first-line treatment for patients with unresectable hepatocellular carcinoma (HCC). However, no studies have reported on specific intestinal microbiota associated with the efficacy of atezolizumab and bevacizumab. In this study, we analyzed fecal samples collected before treatment to investigate the relationship between the intestinal microbiome and the efficacy of atezolizumab and bevacizumab. A total of 37 patients with advanced HCC who were treated with atezolizumab and bevacizumab were enrolled. Fecal samples were collected from the patients, and they were divided into responder (n = 28) and non-responder (n = 9) groups. We compared the intestinal microbiota of the two groups and analyzed the intestinal bacteria associated with prognosis using QIIME2. The alpha and beta diversities were not significantly different between both groups, and the proportion of microbiota was similar. The relative abundance of Bacteroides stercoris and Parabacteroides merdae was higher in the responder group than in the non-responder group. When the prognosis was analyzed by the presence or absence of those bacteria, patients without both had a significantly poorer prognosis. Differences in intestinal microbiome are involved in the therapeutic effect of atezolizumab and bevacizumab.

8.
Dig Dis Sci ; 69(7): 2573-2585, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38713271

RESUMO

BACKGROUND: Numerous biological interventions and small molecules are used to treat Crohn's disease; however, the effectiveness of these treatments varies largely. Non-responsiveness to biological therapies is associated with interleukin (IL)-18 gene polymorphisms and high IL-18 expression has been implicated in the pathogenesis of Crohn's disease. AIMS: The aim of this study was to elucidate the expression of precursor and mature IL-18 in patients with Crohn's disease who exhibited varied responses to cytokine-targeted treatments and determine whether selective inhibition of mature IL-18 offers a novel therapeutic avenue. METHODS: We generated a monoclonal antibody that specifically recognizes the neoepitope of caspase-cleaved mature IL-18. Expression of precursor and mature IL-18 was analyzed in patients with Crohn's disease. Anti-mature IL-18 monoclonal antibodies were intraperitoneally administered in an acute colitis mouse model, and the disease activity index, body weight loss, tissue pathology, proinflammatory cytokine expression, goblet cell function, and microbiota composition were assessed. RESULTS: Precursor and mature IL-18 expression was upregulated and goblet cell function was impaired in patients with Crohn's disease who were unresponsive to biological therapies. Administration of anti-mature IL-18 antibodies ameliorated induced colitis by repairing goblet cell function and restoring the mucus layer. CONCLUSIONS: The newly developed monoclonal antibody holds promise as a therapeutic alternative for Crohn's disease.


Assuntos
Anticorpos Monoclonais , Doença de Crohn , Células Caliciformes , Interleucina-18 , Interleucina-18/metabolismo , Interleucina-18/imunologia , Animais , Células Caliciformes/imunologia , Células Caliciformes/patologia , Células Caliciformes/efeitos dos fármacos , Humanos , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Camundongos , Doença de Crohn/imunologia , Doença de Crohn/tratamento farmacológico , Feminino , Masculino , Modelos Animais de Doenças , Colite/imunologia , Colite/tratamento farmacológico , Adulto , Camundongos Endogâmicos C57BL
9.
Microorganisms ; 12(3)2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38543661

RESUMO

We investigated the prognostic role of the gut microbiome and clinical factors in chronic liver disease (hepatitis, cirrhosis, and hepatocellular carcinoma [HCC]). Utilizing data from 227 patients whose stool samples were collected over the prior 3 years and a Cox proportional hazards model, we integrated clinical attributes and microbiome composition based on 16S ribosomal RNA sequencing. HCC was the primary cause of mortality, with the Barcelona Clinic Liver Cancer staging system-derived B/C significantly increasing the mortality risk (hazard ratio [HR] = 8.060; 95% confidence interval [CI]: 3.6509-17.793; p < 0.001). Cholesterol levels < 140 mg/dL were associated with higher mortality rates (HR = 4.411; 95% CI: 2.0151-9.6555; p < 0.001). Incertae sedis from Ruminococcaceae showed a protective effect, reducing mortality risk (HR = 0.289; 95% CI: 0.1282 to 0.6538; p = 0.002), whereas increased Veillonella presence was associated with a higher risk (HR = 2.733; 95% CI: 1.1922-6.2664; p = 0.017). The potential of specific bacterial taxa as independent prognostic factors suggests that integrating microbiome data could improve the prognosis and treatment of chronic liver disease. These microbiome-derived markers have prognostic significance independently and in conjunction with clinical factors, suggesting their utility in improving a patient's prognosis.

10.
Dig Liver Dis ; 56(6): 941-950, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38413348

RESUMO

INTRODUCTION: Nonampullary duodenal epithelial tumors are rare, but their prevalence is increasing. Various gastrointestinal cancers have been associated with microbiomes. We evaluated the characteristics of the salivary and duodenal microbiomes of patients with nonampullary duodenal epithelial tumors. METHODS: Saliva and biopsy samples from the duodenal bulb and descending portion were obtained from 15 patients with nonampullary duodenal epithelial tumors and 10 controls. Next-generation sequencing was performed to identify bacteria for comparison. RESULTS: Saliva samples had higher Amplicon Sequence Variants (ASVs) and more observed species than duodenal samples. Saliva samples from patients with nonampullary duodenal epithelial tumor were dominated by Bacteroidetes and Prevotella, whereas Proteobacteria and Neisseria were dominant in the control samples. The relative abundance of bacteria was higher in patients with nonampullary duodenal epithelial tumors. Most bacteria were classified as bacteria of oral origin. Oribacterium and Stomatobaculum were significantly higher in the saliva, duodenal bulb, and descending portion of patients with nonampullary duodenal epithelial tumors. CONCLUSION: Patients with nonampullary duodenal epithelial tumors had different salivary and duodenal microbiomes than controls. Bacteria types differed between groups at each site, and most bacteria of oral origin were more abundant in patients with nonampullary duodenal epithelial tumors.


Assuntos
Neoplasias Duodenais , Duodeno , Saliva , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Saliva/microbiologia , Neoplasias Duodenais/microbiologia , Neoplasias Duodenais/patologia , Idoso , Duodeno/microbiologia , Duodeno/patologia , Estudos de Casos e Controles , Microbioma Gastrointestinal , Adulto , Prevotella/isolamento & purificação , Prevotella/genética , Sequenciamento de Nucleotídeos em Larga Escala , Bacteroidetes/isolamento & purificação , Bacteroidetes/genética , Bactérias/isolamento & purificação , Bactérias/genética , Bactérias/classificação
11.
J Gastroenterol Hepatol ; 39(3): 480-488, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38149305

RESUMO

BACKGROUND AND AIM: Potassium-competitive acid blockers more strongly suppress the gastric acid barrier than proton pump inhibitors and cause dysbiosis. However, preventive measures in this regard have not been established. We aimed to evaluate whether 1-kestose, a known prebiotic, was effective at alleviating dysbiosis caused by potassium-competitive acid blockers. METHODS: Patients scheduled to undergo endoscopic resection for superficial gastroduodenal tumors were enrolled and randomized 1:1 to receive either 1-kestose or placebo. All patients were started on potassium-competitive acid blocker (vonoprazan 20 mg/day) and took 1-kestose 10 g/day or placebo (maltose) 5 g/day for 8 weeks. The primary outcome was the effect of 1-kestose on potassium-competitive acid blocker-induced alterations in the microbiome. The fecal microbiome was analyzed before and after potassium-competitive acid blocker treatment via MiSeq (16S rRNA gene V3-V4 region). RESULTS: Forty patients were enrolled, and 16 in each group were analyzed. In the placebo group, the Simpson index, an alpha diversity, was significantly decreased and relative abundance of Streptococcus was significantly increased by 1.9-fold. In the kestose group, the Simpson index did not change significantly and relative abundance of Streptococcus increased 1.3-fold, but this was not a significant change. In both groups, no adverse events occurred, ulcers were well healed, and pretreatment and posttreatment short-chain fatty acid levels did not differ. CONCLUSIONS: The potassium-competitive acid blocker caused dysbiosis in the placebo group; this effect was prevented by 1-kestose. Thus, 1-kestose may be useful in dysbiosis treatment.


Assuntos
Disbiose , Microbiota , Pirróis , Sulfonamidas , Trissacarídeos , Humanos , Disbiose/etiologia , RNA Ribossômico 16S , Projetos Piloto , Inibidores da Bomba de Prótons/efeitos adversos , Potássio
12.
Inflamm Bowel Dis ; 30(8): 1353-1366, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38141180

RESUMO

BACKGROUND: Antitumor necrosis factor (TNF)-α antibodies have improved the outcome of inflammatory bowel disease (IBD); but half of patients remain unresponsive to treatment. Interleukin-18 (IL-18) gene polymorphism is associated with resistance to anti-TNF-α antibodies, but therapies targeting IL-18 have not been clinically applied. Only the mature protein is biologically active, and we aimed to investigate whether specific inhibition of mature IL-18 using a monoclonal antibody (mAb) against a neoepitope of caspase-cleaved mature IL-18 could be an innovative treatment for IBD. METHODS: The expression of precursor and mature IL-18 in patients with UC was examined. Colitis was induced in C57/BL6 mice by administering dextran sulfate sodium (DSS), followed by injection with anti-IL-18 neoepitope mAb. Colon tissues were collected and subjected to histological analysis, immunohistochemistry, immunoblotting, and quantitative polymerase chain reaction. Colon epithelial permeability and microbiota composition were analyzed. RESULTS: Mature IL-18 expression was elevated in colon tissues of patients with active ulcerative colitis. Administration of anti-IL-18 neoepitope mAb ameliorated acute and chronic DSS-induced colitis; reduced interferon-γ, TNF-α, and chemokine (CXC motif) ligand-2 production and epithelial cell permeability; promoted goblet cell function; and altered the intestinal microbiome composition. The suppressive effect of anti-IL-18 neoepitope mAb was superior to that of anti-whole IL-18 mAb. Furthermore, combination therapy with anti-TNF-α Ab suppressed acute and chronic colitis additively by suppressing cytokine expressions and reducing cell permeability by upregulating claudin1 and occludin expression. CONCLUSIONS: Anti-IL-18 neoepitope mAb ameliorates acute and chronic colitis, suggesting that this mAb will be an innovative therapeutic option for IBD.


We investigate a novel monoclonal antibody that specifically recognizes a neoepitope of caspase-cleaved IL-18 and alleviates dextran sulfate sodium-induced colitis by suppressing the secretion of inflammatory cytokines, improving intestinal epithelial permeability, promoting goblet cell function, and regulating intestinal microbiota.


Assuntos
Anticorpos Monoclonais , Sulfato de Dextrana , Interleucina-18 , Mucosa Intestinal , Camundongos Endogâmicos C57BL , Animais , Feminino , Humanos , Masculino , Camundongos , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/imunologia , Colo/patologia , Colo/metabolismo , Colo/imunologia , Modelos Animais de Doenças , Interleucina-18/metabolismo , Interleucina-18/imunologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo
13.
Nagoya J Med Sci ; 85(4): 648-658, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38155621

RESUMO

Endoscopic papillectomy is widely performed to treat duodenal papillary tumors, particularly at high-volume centers. It is indicated for adenomas without intraductal extension of the bile or pancreatic ducts. However, despite numerous reports of carcinomas that expand the indications to include well-differentiated adenocarcinomas that do not invade the sphincter of Oddi, the low agreement between biopsy and final pathological diagnosis, as well as the current inability of imaging modalities to diagnose sphincter of Oddi invasion, makes it difficult to consider expanding indications. Although complications can be prevented by certain methods, such as pancreatic duct stenting, and the frequency of severe complications has decreased, the safety of the procedure remains unconfirmed. In the future, this technology is expected to progress and enable wider applications, including those in tumors with extensive horizontal spread and those with intraductal extension of the bile and pancreatic ducts. Such technology may also improve the safety and accuracy of diagnosis.


Assuntos
Adenocarcinoma , Ampola Hepatopancreática , Humanos , Ampola Hepatopancreática/cirurgia , Ampola Hepatopancreática/patologia , Endoscopia/métodos , Ductos Pancreáticos , Biópsia , Adenocarcinoma/patologia , Resultado do Tratamento
14.
Nagoya J Med Sci ; 85(3): 402-427, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37829481

RESUMO

Ustekinumab has recently been approved for the treatment of ulcerative colitis (UC) based on data from clinical trials. However, the effectiveness of ustekinumab in patients with UC in a real-world setting remains unclear. Hence, in this meta-analysis, we aimed to evaluate the effectiveness of ustekinumab in a real-world setting and to investigate the predictors of its effectiveness. A comprehensive literature search was performed to examine the effectiveness of ustekinumab in UC patients admitted between January 2019 and December 2021. Data on clinical remission, response, and corticosteroid-free clinical remission rates were extracted, pooled, and analyzed. Meta-regression analysis was performed to investigate the source of heterogeneity and the impact of moderators on the outcomes of interest. A total of 14 eligible studies were identified. The pooled clinical remission rate was 55.0% at week 8, 36.1% at week 16, 46.6% at month 6, and 38.6% at month 12. The meta-regression analysis showed that prior use of anti-tumor necrosis factor (TNF) agents and vedolizumab and the publication style were significant moderators. Additionally, out of 258 patients, there were 28 adverse events (AEs) (10.9%). The effectiveness of ustekinumab in real-world patients with UC was consistent with the results clinical trials. Moreover, previous treatment with anti-TNF agents and vedolizumab might have affected the effectiveness of ustekinumab.


Assuntos
Colite Ulcerativa , Ustekinumab , Humanos , Ustekinumab/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/induzido quimicamente , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Resultado do Tratamento , Indução de Remissão , Fator de Necrose Tumoral alfa/uso terapêutico
15.
Hepatol Int ; 17(6): 1378-1392, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37666952

RESUMO

BACKGROUND: Elevated bile acid levels have been associated with liver tumors in fatty liver. Ileal bile acid transporter inhibitors may inhibit bile acid absorption in the distal ileum and increase bile acid levels in the colon, potentially decreasing the serum and hepatic bile acid levels. This study aimed to investigate the impact of these factors on liver tumor. METHODS: C57BL/6J mice received a one-time intraperitoneal injection of 25-mg/kg diethylnitrosamine. They were fed a choline-deficient high-fat diet for 20 weeks starting from 8 weeks of age, with or without elobixibat (EA Pharma, Tokyo, Japan). RESULTS: Both groups showed liver fat accumulation and fibrosis, with no significant differences between the two groups. However, mice with elobixibat showed fewer liver tumors. The total serum bile acid levels, including free, tauro-conjugated, glyco-conjugated, and tauro-α/ß-muricholic acids in the liver, were noticeably reduced following elobixibat treatment. The proportion of gram-positive bacteria in feces was significantly lower in the group treated with elobixibat (5.4%) than in the group without elobixibat (33.7%). CONCLUSION: Elobixibat suppressed tumor growth by inhibiting bile acid reabsorption, and decreasing total bile acid and primary bile acid levels in the serum and liver. Additionally, the presence of bile acids in the colon may have led to a significant reduction in the proportion of gram-positive bacteria, potentially resulting in decreased secondary bile acid synthesis.


Assuntos
Neoplasias Hepáticas , Microbiota , Hepatopatia Gordurosa não Alcoólica , Camundongos , Animais , Ácidos e Sais Biliares , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/patologia , Camundongos Endogâmicos C57BL , Fígado/patologia
16.
BMC Gastroenterol ; 23(1): 290, 2023 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-37620810

RESUMO

BACKGROUND: Obscure gastrointestinal bleeding refers to bleeding for which the source cannot be ascertained even through balloon-assisted endoscopy. In certain instances, Dieulafoy's lesion in the small bowel is presumed to be the underlying cause. AIM: This retrospective study aimed to elucidate the clinical characteristics of Dieulafoy's lesion in the small bowel as diagnosed via double-balloon endoscopy while also exploring the feasibility of predicting bleeding from Dieulafoy's lesion prior to endoscopy in cases of obscure gastrointestinal bleeding. METHODS: A comprehensive analysis of our database was conducted, identifying 38 patients who received a diagnosis of Dieulafoy's lesion and subsequently underwent treatment via double-balloon endoscopy. The clinical background, diagnosis, and treatment details of patients with Dieulafoy's lesion were carefully examined. RESULTS: The median age of the 38 patients was 72 years, and 50% of the patients were male. A total of 26 (68%) patients exhibited a high comorbidity index. The upper jejunum and lower ileum were the most frequently reported locations for the occurrence of Dieulafoy's lesion in the small bowel. The detected Dieulafoy's lesions exhibited active bleeding (n = 33) and an exposed vessel with plaque on the surface (n = 5). Rebleeding after endoscopic treatment occurred in 8 patients (21%, median period: 7 days, range: 1-366 days). We conducted an analysis to determine the definitive nature of the initial double-balloon endoscopy diagnosis. Multivariate analysis revealed that hematochezia of ≥ 2 episodes constituted the independent factor associated with ≥ 2 double-balloon endoscopy diagnoses. Additionally, we explored factors associated with rebleeding following endoscopic treatment. Although the number of hemoclips utilized displayed a likely association, multivariate analysis did not identify any independent factor associated with rebleeding. CONCLUSION: If a patient encounters multiple instances of hematochezia, promptly scheduling balloon-assisted endoscopy, equipped with optional instruments without delay is advised, after standard endoscopic evaluation with esophagogastroduodenoscopy and colonoscopy is unrevealing.


Assuntos
Endoscopia Gastrointestinal , Intestino Delgado , Humanos , Masculino , Idoso , Feminino , Estudos Retrospectivos , Intestino Delgado/diagnóstico por imagem , Colonoscopia , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/terapia
17.
J Gastroenterol ; 58(10): 1015-1029, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37561155

RESUMO

BACKGROUND: The degree of immune response to COVID-19 vaccination in inflammatory bowel disease (IBD) patients based on actual changes in anti-SARS-CoV-2 antibody titres over time is unknown. METHODS: Data were prospectively acquired at four predetermined time points before and after two vaccine doses in a multicentre observational controlled study. The primary outcome was humoral immune response and vaccination safety in IBD patients. We performed trajectory analysis to identify the degree of immune response and associated factors in IBD patients compared with controls. RESULTS: Overall, 645 IBD patients and 199 control participants were analysed. At 3 months after the second vaccination, the seronegative proportions were 20.3% (combination of anti-tumour necrosis factor [TNF]α and thiopurine) and 70.0% (triple combination including steroids), despite that 80.0% receiving the triple combination therapy were seropositive at 4 weeks after the second vaccination. Trajectory analyses indicated three degrees of change in immune response over time in IBD patients: high (57.7%), medium (35.6%), and persistently low (6.7%). In the control group, there was only one degree, which corresponded with IBD high responders. Older age, combined anti-TNFα and thiopurine (odds ratio [OR], 37.68; 95% confidence interval [CI], 5.64-251.54), steroids (OR, 21.47; 95%CI, 5.47-84.26), and tofacitinib (OR, 10.66; 95%CI, 1.49-76.31) were factors associated with persistently low response. Allergy history (OR, 0.17; 95%CI, 0.04-0.68) was a negatively associated factor. Adverse reactions after the second vaccination were significantly fewer in IBD than controls (31.0% vs 59.8%; p < 0.001). CONCLUSIONS: Most IBD patients showed a sufficient immune response to COVID-19 vaccination regardless of clinical factors. Assessment of changes over time is essential to optimize COVID-19 vaccination, especially in persistently low responders.


Assuntos
COVID-19 , Doenças Inflamatórias Intestinais , Humanos , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , Doenças Inflamatórias Intestinais/tratamento farmacológico , Estudos Prospectivos , Vacinação
18.
J Gastroenterol Hepatol ; 38(9): 1647-1655, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37328944

RESUMO

BACKGROUND AND AIM: There is currently no established number of actuations (to-and-fro movements) per pass during endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB). This study aimed to compare 15 vs 5 actuations in terms of adequate specimen acquisition of solid pancreatic lesions. METHODS: In this prospective, randomized, crossover, noninferiority, single-center study, eligible patients underwent EUS-FNB using a 22-G Franseen needle with both 15 and 5 actuations per pass, performed in a randomized order, from October 2020 to December 2021. The acquired specimens from each pass were separately evaluated. The primary outcome was the accuracy of the histological diagnosis per pass. The noninferiority margin was set as 15%. RESULTS: Data from 85 patients were analyzed, revealing pancreatic cancer in 73 patients. The accuracy of the histological diagnosis in the 15 and 5 actuations groups was 83.5% (71/85) and 77.7% (66/85), respectively. The difference was -5.8% (95% confidence interval -15.6-3.4), which does not indicate noninferiority of the five actuations group. Among the secondary outcomes, the 15 actuations group was significantly superior to the five actuations group in terms of the obtained core tissues (1.88 [interquartile range 0.89-3.64] mm2 vs 1.66 [0.83-2.71] mm2 [P = 0.031]) and subjective evaluation of cytology specimens for pancreatic cancer (69.0% vs. 31.0%, P = 0.005). CONCLUSIONS: The noninferiority of five actuations in the accuracy of the histological diagnosis was not confirmed, and 15 actuations are preferred during EUS-FNB for solid pancreatic lesions.


Assuntos
Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Neoplasias Pancreáticas , Humanos , Estudos Prospectivos , Pâncreas/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas
19.
J Gastroenterol Hepatol ; 38(5): 761-767, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36648892

RESUMO

BACKGROUND AND AIM: Double-balloon endoscopic retrograde cholangiography (DBERC) is a valuable procedure for patients with altered gastrointestinal anatomy. Nonetheless, it is time-consuming and burdensome for both patients and endoscopists, partly because route selection in the reconstructed bowel with complicating loop is challenging. Carbon dioxide insufflation enterography is reportedly useful for route selection in the blind loop. This prospective randomized clinical trial investigated the usefulness of carbon dioxide insufflation enterography for route selection by comparing it with conventional observation. METHODS: Patients scheduled to undergo DBERC were consecutively registered. They were divided into carbon dioxide insufflation enterography and conventional groups via randomization according to stratification factors, type of reconstruction methods, and experience with DBERC. The primary endpoint was the correct rate of initial route selection. The secondary endpoints were the insertion time, examination time, amount of anesthesia drugs, and complications. RESULTS: The correct rate of route selection was significantly higher in the carbon dioxide insufflation enterography group (23/25, 92%) than in the visual method (15/25, 60%) (P = 0.018). The insertion time was significantly shorter in the carbon dioxide insufflation enterography group than in the visual group (10.8 ± 11.1 min vs 29.8 ± 15.7 min; P < 0.001). No significant differences in complications were noted between the two groups. The amounts of sedatives and analgesics used were significantly lower in the carbon dioxide insufflation enterography group (P < 0.001 and P < 0.001, respectively). CONCLUSIONS: Carbon dioxide insufflation enterography can reduce the burden of DBERC on patients and endoscopists by shortening the examination time and reducing the amount of medication.


Assuntos
Dióxido de Carbono , Insuflação , Humanos , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Estudos Prospectivos , Endoscopia Gastrointestinal/métodos , Colangiografia , Insuflação/métodos
20.
Digestion ; 104(3): 202-211, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36603569

RESUMO

INTRODUCTION: Eosinophils in the esophageal epithelium are unevenly distributed in eosinophilic esophagitis (EoE). Esophageal eosinophilia (EE) may be observable by endocytoscopy (EC). This study aimed to evaluate the diagnostic performance of EC for the diagnosis of EE. METHODS: A total of 33 EoE patients underwent EC with methylene blue staining from March 2020 to April 2021. A total of 194 EC images with corresponding biopsies were obtained. Three findings of EC, increased squamous cells (item I), increased inflammatory cells (item II), and cells with bilobed nuclei (item III), were established. These findings were reviewed by two endoscopists to diagnose EE. Another four endoscopists reviewed the images for interobserver agreement. RESULTS: When all three items were met by EC, the sensitivity and the accuracy for the diagnosis of EE were 88% and 76%, respectively. The integrated diagnostic odds ratios (ORs) for the diagnosis of EE of the four endoscopists were significant (OR: 3.98, 95% CI: 2.94-5.40, p < 0.001). The results were similar when only item III was met. Interobserver agreement was good for item III to diagnose EE (kappa value = 0.653). DISCUSSION/CONCLUSION: The diagnostic performance of EC for EE is acceptable and has good interobserver agreement. It may be useful for targeted biopsy in EoE patients.


Assuntos
Esofagite Eosinofílica , Humanos , Esofagite Eosinofílica/diagnóstico por imagem , Esofagite Eosinofílica/patologia , Endoscopia , Biópsia
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