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Background/Objectives: We aimed to determine the trends over time and current status of early Helicobacter pylori-uninfected gastric cancer (HpUIGC) treatment in a region with an aging population. Methods: This retrospective, multi-center observational study was conducted at seven major general hospitals in Kagoshima Prefecture. From January 2009 to July 2022, 2091 patients who received endoscopic resection (ER) for early gastric cancer (EGC) were retrospectively enrolled, of which 35 were identified as early HpUIGC cases. Results: The number of ERs for EGC demonstrated a significant increasing trend from 2010 to 2021 (p = 0.01 for trend). Furthermore, the 12-year period from 2010 to 2021 was divided into an early and late phase every 6 years. In the early phase, there were 5 cases (0.7%) of early HpUIGC, while in the late phase, there were 25 cases (2.1%), indicating a significant increase in the proportion of ERs for early HpUIGC cases in the late phase (p = 0.02). Conclusions: The proportion of ERs for early HpUIGC, which are more common in relatively young patients, may be increasing as a proportion of all ERs for GC, even in areas of Japan with an aging population.
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A 75-year-old woman was diagnosed with clinical stage III lung cancer. The patient was treated with chemoradiotherapy and subsequent durvalumab, an anti-PD-L1 antibody immune checkpoint inhibitor (ICI). Liver dysfunction was observed 14 days after the start of durvalumab therapy (aspartate transaminase, 218U/l;alanine aminotransferase, 169U/l). This corresponded to a grade 3 adverse event according to the Common Terminology Criteria for Adverse Events. The second course of durvalumab was withheld. The patient was hospitalized 31 days after durvalumab therapy because of worsening liver dysfunction. Laboratory findings and imaging examinations suggested liver injury due to an immune-related adverse event (irAE). Liver biopsy performed 38 days after durvalumab therapy showed severe lymphocyte and plasma cell infiltration into the portal tract, focal necrosis in the hepatic lobules, and necrotic changes around the hepatic lobules. These findings were similar to those of autoimmune hepatitis (AIH). Immunohistochemical results revealed infiltration of CD3- and CD8-positive lymphocytes and mild infiltration of CD4-positive lymphocytes. Pathological findings in the liver tissue were consistent with an irAE. Jaundice worsened and the prothrombin time was prolonged, leading to a risk of progression to liver failure. Thus, pulse steroid therapy was performed with methylprednisolone (mPSL) starting at 0.8mg/kg. Liver dysfunction lessened and the mPSL dose was gradually reduced. Moreover, ICIs exert antitumor effects by inhibiting the immune checkpoint system but can cause irAEs in various organs. Liver injury is also relatively common. Liver tissue findings are similar to those in AIH, but immunostaining reveals the presence of numerous CD8-positive lymphocytes. Fewer CD4-positive lymphocytes exist in irAE-associated liver injury than in AIH. Medical departments must cooperate and effectively manage irAEs because ICIs are increasingly being used and can occur in organs throughout the body. In principle, irAEs are treated with steroids. Thus, high-dose steroids diminishing the therapeutic effect of ICIs is a concern, and it is important to control irAEs with low-dose steroids that are started earlier.
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Antineoplásicos Imunológicos , Hepatopatias , Falência Hepática , Neoplasias Pulmonares , Idoso , Antineoplásicos Imunológicos/efeitos adversos , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológicoRESUMO
Hyperammonemia is often experienced as a complication of liver cirrhosis, but it is not well known that hyperammonemic encephalopathy is induced by urease-splitting bacteria in the urinary tract. We report two cases of hyperammonemia in two women in their 80s with liver cirrhosis. Both cases were treated as hepatic encephalopathy with usual treatment, but there was no improvement. Urinalysis showed marked alkalinuria and urine culture showed urease-splitting bacteria, which were thought to be related to the pathology. After drainage of urine and administration of antimicrobials, the blood ammonia level decreased and the urine pH level normalized. The mechanism of this is that ammonia is produced by the degradation of urinary urea by urease-producing bacteria in the bladder, and in the presence of dysuria, it is absorbed into the blood circulation from the bladder venous plexus, leading to hyperammonemia.Urine findings should be confirmed when a patient with liver disease develops hyperammonemia or is unresponsive to conventional hepatic encephalopathy treatment.
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Encefalopatia Hepática , Infecções Urinárias , Bactérias , Feminino , Encefalopatia Hepática/etiologia , Humanos , Cirrose Hepática/complicações , Urease , Infecções Urinárias/complicações , Infecções Urinárias/tratamento farmacológicoRESUMO
BACKGROUND AND AIMS: Hexanoyl (Hx:C6) group-modified alkaline-treated gelatin porous film (HAG) is a newly developed degradable hydrogel characterized by strong adhesiveness and high affinity for vascular endothelial growth factor (VEGF). The aim of this study was to clarify the effect of HAG sheets on the healing process of post-endoscopic submucosal dissection (ESD) porcine gastric artificial ulcers. METHODS: (1) To evaluate the adhesiveness of HAG sheets over time, we performed ESD to create 1 artificial ulcer and covered the lesion with 1 HAG sheet using 1 miniature swine. We observed 2 ulcers by endoscopic and microscopic examinations. (2) To examine the effect of HAG sheets on post-ESD ulcer healing, we performed ESD using 5 miniature swine. The artificial ulcers were covered with HAG sheets, or left uncovered after ESD (day 0), followed by macroscopic and microscopic examinations. On days 7 and 14, we observed 2 ulcers by endoscopic examinations. On day 14, the animals were sacrificed, and histological examination was performed on the 3 stomachs that could be extirpated. RESULTS: (1) On day 7, adhesion of HAG sheets was observed. (2) Gastric ulcer area on day 7 was significantly larger in the covered ulcers than in the non-covered ulcers (p = 0.046). On day 14, although there was no significant difference in ulcer area irrespective of covering (p = 0.357), the covered ulcers tended to repair less fold convergence than non-covered ulcers. The covered ulcer sheets significantly decreased inflammatory cell infiltration (p = 0.011), but significantly increased the abundance of macrophages (p = 0.033), in submucosal layers. Also, the abundance of alpha-smooth muscle actin-positive cells in submucosal layers of the covered ulcers was significantly reduced (p = 0.044), leading to a decrease in collagen accumulation. In addition, fibrosis and atrophy of the muscularis propria were significantly lower for covered ulcers than for non-covered ulcers. Furthermore, microvessels and VEGF-positive cells were significantly more abundant in the submucosal layers of the covered ulcers (p < 0.001 and p = 0.024, respectively). CONCLUSIONS: HAG sheets induced post-ESD ulcer healing with less submucosal inflammation and muscularis propria injury and have the potential to decrease excess scarring.
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Ressecção Endoscópica de Mucosa , Neoplasias Gástricas , Úlcera Gástrica , Animais , Ressecção Endoscópica de Mucosa/efeitos adversos , Fibrose , Gelatina , Inflamação/prevenção & controle , Porosidade , Inibidores da Bomba de Prótons , Úlcera Gástrica/etiologia , Suínos , Porco Miniatura , Úlcera/etiologia , Úlcera/prevenção & controle , Fator A de Crescimento do Endotélio VascularRESUMO
Gallbladder neuroendocrine carcinoma (NEC) is a rare gallbladder tumor. The current report is a case of a patient preoperatively diagnosed with gallbladder NEC using somatostatin receptor scintigraphy (SRS). A 63-year-old man was admitted to our hospital by a family doctor after abdominal ultrasonography revealed thickened walls of the neck of his gallbladder. At Kagoshima University Hospital, CT and MRI of the abdomen and endoscopic ultrasonography confirmed the thickening of the walls of the neck of the gallbladder. However, it did not resemble a typical gallbladder cancer or tumor, such as a neuroendocrine tumor or malignant lymphoma. Positron emission tomography and SRS showed abnormal accumulation at the tumor site. Endoscopic retrograde cholangiopancreatography was performed, adenocarcinoma was suspected based on intra-gallbladder bile cytology, and a cholecystectomy with lymphadenectomy was performed. The postoperative pathological diagnosis was small cell NEC (pT3a, N0, M0, stage II). Immunohistochemistry indicated that the gallbladder tumor cells were positive for synaptophysin, chromogranin A, and cluster of differentiation (CD) 56, and negative for somatostatin receptors (SSTR) 2 and 5. Gene expression assays revealed the expression of all SSTR subtypes (SSTR1-5) in the tumor. Generally, NECs exhibit poor accumulation in SRS, however, the results of the current case suggest that SRS may be useful in the preoperative diagnosis of NEC.
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Background and aims Recent studies recommend histological mucosal healing of intestinal tissue as a treatment goal in ulcerative colitis (UC). Linked-color imaging (LCI) is a new endoscopy system that enhances the color differences of the gastrointestinal mucosa. We investigated the efficacy of LCI in the evaluation of intestinal activity, including the histological activity in UC. Method A total of 21 UC patients who were evaluated by the LASEREO system (FUJIFILM Co., Tokyo, Japan) were enrolled from August to December in 2016. All of the target points were observed by conventional white-light imaging (WLI) and LCI and biopsied from the region of interest in each view. We quantified the color tones of 73 biopsied points on WLI and LCI using the L*a*b* color value (WLI-L, WLI-a, WLI-b, and LCI-L, LCI-a, LCI-b). We then investigated the relationships among the L*a*b* color values, endoscopic findings, and histological healing. Results The average LCI-a and LCI-b values of patients with high mucosal activity disease were significantly higher than in those with mucosal healing ( P â<â0.01), and only LCI-a was significantly correlated with the score for histological healing. With regard to the other color values (LCI-L and all WLI values), there were no statistically significant differences in terms of average color value and correlation between patients with high mucosal activity and those with mucosal healing. In addition, the difference in the average color values with LCI and WLI was 7.1 and 3.1, respectively. Conclusion LCI is more useful than WLI for the visualization and evaluation of mucosal inflammation in UC.
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RATIONALE: Minimally invasive surgery is used to treat early colorectal tumors. Endoscopic submucosal dissection (ESD) for resection of tumors extending above the dentate line (particularly those with concomitant hemorrhoids) is technically difficult. We present a case of a patient with a lower rectal adenoma extending above the dentate line, which underwent combined ESD and transanal minimally invasive surgery (TAMIS) to achieve accurate excision and prevent complications. PATIENT CONCERNS: A 68-year-old man with a history of blood in stool over 2 to 3 years underwent colonoscopy, which revealed an adenoma measuring 3âcm in size in the lower rectum extending above the dentate line. The part extending above the dentate line was a type Is lesion and that of oral side was a type IIa lesion. Histopathologically, the lesion was diagnosed as a low-grade intramucosal tubulovillous adenoma. DIAGNOSIS: Intramucosal low-grade adenoma with sessile polyp (type Is). INTERVENTIONS: The cranial portion of the lesion was dissected via ESD and the anal portion via TAMIS with minimal bleeding. En bloc resection of the tumor was performed. OUTCOMES: His postoperative period was uneventful, and he was discharged and regularly followed-up. LESSONS: Combined ESD and TAMIS is effective in patients with benign and early neoplastic lesions of the anorectum extending above the dentate line with concomitant hemorrhoids and can prevent complications.
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Adenoma/cirurgia , Ressecção Endoscópica de Mucosa , Neoplasias Retais/cirurgia , Cirurgia Endoscópica Transanal , Adenoma/diagnóstico por imagem , Adenoma/patologia , Idoso , Diagnóstico Diferencial , Ressecção Endoscópica de Mucosa/métodos , Humanos , Masculino , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/patologia , Cirurgia Endoscópica Transanal/métodosRESUMO
An 87-year-old bedridden woman developed intestinal obstruction caused by an enterolith or bezoar. Since the patient refused surgery, we administered 1,000 mL/day of cola via an ileus tube to dissolve the stone. Occlusion of the small intestine disappeared on day 6. The excreted stones contained calcium phosphate, which is typical of enteroliths. We later confirmed that the retrieved stones could be dissolved in cola (Coca-Cola®, pH 1.9) as well as 0.10 and 0.010 mol/L hydrochloric acid (pH 1.0 and 2.0, respectively) and food-grade vinegar (pH 2.6). These findings suggest that the enteroliths were dissolved by an acid-base reaction.
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Cálculos/complicações , Cálculos/tratamento farmacológico , Cola , Íleus/etiologia , Obstrução Intestinal/etiologia , Idoso de 80 Anos ou mais , Feminino , Humanos , Concentração de Íons de Hidrogênio , Intestino Delgado , SolubilidadeRESUMO
BACKGROUND/AIMS: Esophageal mucosal damage often causes scar tissue, leading to refractory stricture. The aim of this study was to clarify the effect of hepatocyte growth factor (HGF) on esophageal mucosal repair and fibrosis leading to stricture in a rat model of esophageal ulcer. METHODS: Esophageal ulcers were induced in rats by topical exposure of the lower esophageal serosa to acetic acid, followed by intraperitoneal administration of HGF (200 µg/day) using an osmotic pump for 7 days. The effect of HGF on esophageal mucosal injury was investigated macroscopically and microscopically. The effect of HGF on epithelial cell proliferation and the expression of genes closely associated with the development of fibrosis were also examined. RESULTS: The administration of HGF for 7 days led to a significant reduction in the ulcerative area and enhanced the proliferation of esophageal epithelial cells. HGF treatment significantly decreased the fibrosis, and subsequently attenuated not only the foreshortening but also the narrowing of the esophagus. The expression levels of tissue inhibitor of metalloproteinase (TIMP)-1, -2, and matrix metalloproteinase (MMP)-2, -9 were significantly decreased among rats treated with HGF. CONCLUSION: HGF facilitates the repair of esophageal mucosal injury and may also ameliorate the esophageal fibrosis, possibly through enhanced re-epithelization.
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Doenças do Esôfago/tratamento farmacológico , Mucosa Esofágica/patologia , Fator de Crescimento de Hepatócito/farmacologia , Úlcera/tratamento farmacológico , Ácido Acético/toxicidade , Animais , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Doenças do Esôfago/induzido quimicamente , Doenças do Esôfago/patologia , Mucosa Esofágica/efeitos dos fármacos , Fibrose/tratamento farmacológico , Fator de Crescimento de Hepatócito/uso terapêutico , Humanos , Masculino , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico , Úlcera/induzido quimicamente , Úlcera/patologiaRESUMO
A 65-year-old man underwent subtotal gastrectomy for advanced gastric cancer. The histological type of the cancer was signet-ring cell carcinoma, and the clinical stage was stage IB (T2N0M0). Three years after surgery, the patient had the following symptoms:dysphagia, odynophagia, and weight loss. Esophageal endoscopy and esophagography revealed a circular stenosis covered with the normal mucosa between the middle esophagus and the esophagogastric junction. Histologically, the samples obtained by staging laparoscopy revealed signet-ring cell carcinoma. Tucker's criteria are an important tool for differentiating secondary achalasia from primary achalasia with clinical value. Therefore, we suggest that staging laparoscopy is useful for the histological diagnosis of recurrent gastric cancer.
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Acalasia Esofágica/diagnóstico , Laparoscopia , Recidiva Local de Neoplasia/diagnóstico , Neoplasias Gástricas/diagnóstico , Idoso , Junção Esofagogástrica , Humanos , MasculinoRESUMO
BACKGROUND AND AIM: There is a paucity of data on the diagnostic efficacy of liquid-based cytology (LBC) for pancreatic samples obtained by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). Using propensity score matching, we retrospectively analyzed the additional diagnostic value of LBC compared to a conventional Papanicolaou smear (CPS) for samples of solid pancreatic lesions obtained by EUS-FNA. METHODS: This cohort study included 126 matched patients who underwent initial EUS-FNA for solid pancreatic lesions between January 2009 and August 2014. CPS was used for cytology of EUS-FNA samples obtained until May 2012 (63 patients). Subsequently, LBC was used for cytological analysis (63 patients). Diagnostic yields of CPS and LBC for malignancy were compared. Risk factors for cytological misdiagnosis with LBC were investigated. RESULTS: Overall rate of malignancy was 86% after matching. LBC had higher diagnostic sensitivity and accuracy than CPS (96.6% vs 84.0%, P = 0.03; and 96.8% vs 87.3%, P = 0.05). LBC was significantly more sensitive for diagnosing pancreatic head lesions (96.4% vs 78.1%, P = 0.04). The sensitivity for pancreatic ductal adenocarcinoma (PDAC) with LBC was higher (98.1% vs 83.0%, P = 0.009). Multivariate analysis revealed that malignant tumors other than PDAC (P = 0.004) and lesion size ≤20 mm (P = 0.046) were risk factors for LBC misdiagnosis in all participants. CONCLUSIONS: For solid pancreatic lesions, LBC of EUS-FNA samples contributes to the diagnosis of malignancy. Malignant tumors other than PDAC and small tumors are difficult to diagnose using EUS-FNA and LBC.
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Carcinoma/patologia , Citodiagnóstico , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Neoplasias Pancreáticas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Pontuação de Propensão , Estudos RetrospectivosRESUMO
Human neutrophil peptides (HNPs) not only have antimicrobial properties, but also exert multiple immunomodulatory effects depending on the concentration used. We have previously demonstrated that the intraperitoneal administration of high-dose HNP-1 (100 µg/day) aggravates murine dextran sulfate sodium (DSS)-induced colitis, suggesting a potential pro-inflammatory role for HNPs at high concentrations. However, the role of low physiological concentrations of HNPs in the intestinal tract remains largely unknown. The aim of this study was to examine the effects of low concentrations of HNPs on intestinal inflammation. We first examined the effects of the mild transgenic overexpression of HNP-1 in DSS-induced colitis. HNP-1 transgenic mice have plasma HNP-1 levels similar to the physiological concentrations in human plasma. Compared to wild-type mice treated with DSS, HNP-1 transgenic mice treated with DSS had significantly lower clinical and histological scores, and lower colonic mRNA levels of pro-inflammatory cytokines, including interleukin (IL)-1ß and tumor necrosis factor (TNF)-α. We then injected low-dose HNP-1 (5 µg/day) or phosphate-buffered saline (PBS) intraperitoneally into C57BL/6N and BALB/c mice administered DSS. The HNP-1-treated mice exhibited significantly milder colitis with reduced expression levels of pro-inflammatory cytokines compared with the PBS-treated mice. Finally, we examined the in vitro effects of HNP-1 on the expression of cytokines associated with macrophage activation. Low physiological concentrations of HNP-1 did not significantly affect the expression levels of IL-1ß, TNF-α, IL-6 or IL-10 in colonic lamina propria mononuclear cells activated with heat-killed Escherichia coli, suggesting that the anti-inflammatory effects of HNP-1 on murine colitis may not be exerted by direct action on intestinal macrophages. Collectively, our data demonstrated a biphasic dose-dependent effect of HNP-1 on DSS-induced colitis: an amelioration at low concentrations and an aggravation at high concentrations. Low concentrations of HNPs may contribute to the maintenance of intestinal homeostasis.
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Anti-Inflamatórios/farmacologia , Colite/etiologia , Colite/patologia , alfa-Defensinas/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Colite/tratamento farmacológico , Colite/metabolismo , Citocinas/metabolismo , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Expressão Gênica , Predisposição Genética para Doença , Humanos , Mediadores da Inflamação , Injeções Intraperitoneais , Masculino , Camundongos , Camundongos Transgênicos , alfa-Defensinas/sangue , alfa-Defensinas/genéticaRESUMO
Metabolic syndrome based on insulin resistance (IR) and hypertension is a risk factor for advanced liver disease and cardiovascular disease in patients with nonalcoholic steatohepatitis (NASH). The present study investigated the effects of severe hypertension induced by a highsalt (HS) diet and antihypertensive therapy on the pathophysiological condition of spontaneously hypertensive rats (SHRs) with steatohepatitis. Steatohepatitis was induced using a choline-deficient, L-amino acid-defined diet (CDAA). Male SHRs (7weekold) were randomly divided into five groups: Those receiving 6 weeks of standard chow with a normal salt concentration, followed by an additional 8 weeks of standard chow or CDAA with a normal salt concentration (control and CDAA groups, respectively); and those receiving 6 weeks of standard chow with HS, followed by CDAA with HS for an additional 8 weeks, with or without the antihypertensive agents, amlodipine (Aml) or hydralazine. In the CDAA and CDAA+HS groups, blood pressure was significantly correlated with serum levels of insulin, fasting blood glucose and homeostasis model assessment (HOMA)IR. Antihypertensive therapy ameliorated the elevated glucose, insulin and HOMAIR. Furthermore, the increased levels of serum interleukin (IL)6 following the CDAA+HS diet were attenuated by antihypertensive therapy. The serum levels of IL10 were increased by antihypertensive therapy, and the decrease in the proportion of splenic CD4+CD25+forkhead box P3+ T cells observed following the CDAA+HS diet tended to be restored by Aml. In conclusion, antihypertensive therapy improved glucose metabolism and imbalances in cytokine expression in the rat model of hypertension with steatohepatitis, suggesting that antihypertensive therapy acting through immunological factors may be beneficial for patients with metabolic syndrome-associated NASH.
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Anti-Hipertensivos/farmacologia , Resistência à Insulina , Interleucina-10/sangue , Interleucina-6/sangue , Hepatopatia Gordurosa não Alcoólica/metabolismo , Animais , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Biomarcadores , Glicemia/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Quimiocina CCL2/metabolismo , Dieta , Modelos Animais de Doenças , Hipertensão/complicações , Hipertensão/fisiopatologia , Insulina/sangue , Insulina/metabolismo , Masculino , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Ratos , Ratos Endogâmicos SHR , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismoRESUMO
BACKGROUND/AIM: Fecal markers have recently been found to provide convenient and noninvasive assessment of intestinal inflammation in inflammatory bowel disease (IBD). In this study, we examined the clinical significance of fecal human neutrophil peptides (F-HNP) in the evaluation of IBD disease activity. METHODS: This study enrolled 70 patients with IBD, consisting of 45 patients with ulcerative colitis (UC), 25 patients with Crohn's disease (CD), and 11 non-IBD controls. Stools samples were evaluated for the association between F-HNP concentration and disease and endoscopic activity in each group and the correlation between F-HNP and fecal calprotectin (F-CP) concentrations. RESULTS: Median F-HNP levels were as follows: UC: 25.6 ng/ml; CD: 20.1 ng/ml; and non-IBD controls: 4.9 ng/ml. F-HNP levels were significantly higher in each IBD group, especially in the UC group, than in the control group. In the UC group, both F-HNP and F-CP levels were significantly higher during active disease compared to the remission phase. Both markers were significantly correlated with the Mayo endoscopic score, although the correlation was stronger for F-HNP than for F-CP (r = 0.66 vs. r = 0.54). CONCLUSION: F-HNP is a noninvasive marker that is useful for evaluating UC endoscopic activity.
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Colite Ulcerativa/diagnóstico , Doença de Crohn/diagnóstico , Fezes/química , Complexo Antígeno L1 Leucocitário/análise , alfa-Defensinas/análise , Adolescente , Adulto , Idoso , Biomarcadores/análise , Estudos de Casos e Controles , Criança , Colite Ulcerativa/sangue , Colite Ulcerativa/metabolismo , Colonoscopia , Doença de Crohn/sangue , Doença de Crohn/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Adulto JovemAssuntos
Divertículo/complicações , Enteroscopia de Duplo Balão/métodos , Duodenopatias/terapia , Adesivo Tecidual de Fibrina/uso terapêutico , Perfuração Intestinal/terapia , Ácido Poliglicólico/uso terapêutico , Adesivos Teciduais/uso terapêutico , Duodenopatias/complicações , Humanos , Perfuração Intestinal/complicações , Masculino , Pessoa de Meia-IdadeRESUMO
Human neutrophil peptides (HNPs) are antimicrobial peptides produced predominantly by neutrophils. We have previously reported that HNP 1-3 levels are increased in the sera and plasma of patients with active ulcerative colitis. The increased expression of interleukin-8 (IL-8) has also been demonstrated in the colonic mucosa of patients with active ulcerative colitis. HNPs induce IL-8 in lung epithelial cells and monocytes through the P2Y6 signaling pathway. However, the association between HNPs and IL-8 in the intestinal mucosa has not yet been investigated. In the present study, we investigated the effects of HNP-1 on the production of IL-8 by human intestinal epithelial cells and the underlying signaling mechanisms. We observed a significant increase in IL-8 expression in the human colon carcinoma cell line, Caco-2, following treatment with HNP-1. The non-selective P2 receptor antagonists, suramin and pyridoxal phosphate-6-azo (benzene-2,4-disulfonic acid) tetrasodium salt hydrate (PPADS), significantly blocked the HNP-1-induced expression of IL-8 in the Caco-2 cells. The P2Y6-specific antagonist, MRS2578, led to a significant but partial decrease in IL-8 expression, suggesting that P2 receptors in addition to P2Y6 are involved in the HNP-1-induced production of IL-8 by Caco-2 cells. In agreement with this finding, HNP-1 also significantly increased IL-8 production in the P2Y6-negative human colon cancer cell line, HT-29, and this increase was blocked by treatment with suramin and PPADS. HNP-1 significantly increased the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK) in the HT-29 cells. However, the HNP-1-induced production of IL-8 was suppressed by the ERK1/2 inhibitor, U0126, but not by the p38 MAPK inhibitor, SB203580. In conclusion, our data demonstrate that HNP-1 induces IL-8 production not only through P2Y6, but also through additional P2 receptors via an ERK1/2-dependent mechanism in intestinal epithelial cells.
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Interleucina-8/biossíntese , Mucosa Intestinal/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Receptores Purinérgicos P2/metabolismo , alfa-Defensinas/farmacologia , Células CACO-2 , Humanos , Isotiocianatos/farmacologia , Tioureia/análogos & derivados , Tioureia/farmacologiaRESUMO
Endoscopic submucosal dissection (ESD) enables wider tumor resection compared with endoscopic mucosal resection and en bloc resection of superficial esophageal neoplasms. However, ESD may cause difficult-to-treat stricture of the esophagus, and therefore, prediction of and measures against postoperative esophageal stricture are critical. The aim of this study was to evaluate the effect of ESD on superficial esophageal neoplasms and identify risk factors associated with esophageal stricture after ESD.This study included 165 lesions in 120 patients with superficial esophageal neoplasms, including cancer and neoplasia, who underwent ESD from 2009 to 2013.The complete resection rate of superficial esophageal neoplasms by ESD was 90.9%. After ESD, 22 subjects (18.3%) had symptomatic esophageal stricture, 12 (10.0%) had aspiration pneumonia of grade 2, and 7 (5.8%) had mediastinal emphysema of grade 2. Comparison of the 22 subjects with stricture with the 98 subjects without stricture showed significant differences in the rate of resection of >75% of the esophageal circumference, rate of whole circumference resection, and the required time for resection. The tumor size and the size of the resected tissue sample also differed between the 2 groups. The groups did not differ in age, sex, alcohol intake, and smoking; location, macroscopic, and histological tumor findings; chest pain; or use of anticoagulants for comorbidities. In multivariate analysis, tumor size and whole circumference resection were independent risk factors for stricture. Furthermore, in 45 subjects with resection of >75% of the esophageal circumference, whole resection of the esophagus was the only independent risk factor for stricture.This study suggests that ESD has a strong therapeutic effect on superficial esophageal neoplasms; however, a greater extent of resection of the esophagus increases the risk of postoperative esophageal stricture. Preventive measures against development of postoperative stricture require further study.
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Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/cirurgia , Estenose Esofágica/etiologia , Esofagoscopia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de RiscoRESUMO
An 89-year-old man was admitted to our hospital for thorough investigation of refractory diabetes mellitus, which revealed primary squamous cell carcinoma of the duodenum. After two courses of chemotherapy, follow-up esophagoduodenogastroscopy and duodenal biopsy showed no evidence of tumor. No findings were suggestive of recurrence of the primary lesion 19 months after starting chemotherapy. This case suggests that chemotherapy including TS-1 may be effective for treating unresectable primary squamous cell carcinoma of the duodenum.
Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Duodenais/tratamento farmacológico , Silicatos/uso terapêutico , Titânio/uso terapêutico , Idoso de 80 Anos ou mais , Neoplasias Duodenais/patologia , Duodenoscopia , Humanos , Masculino , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Hepatocyte growth factor (HGF) is essential for epithelial restitution, a process in which epithelial cells rapidly migrate to cover desquamated epithelium after mucosal injury in the gastrointestinal tract. In this study, we aimed to elucidate the molecular mechanisms of the HGF-mediated reconstitution of gastric epithelial structures by analyzing the expression and subcellular dynamics of tight junction proteins. METHODS: We treated human gastric epithelial MKN74 cells with HGF, and examined the effects of HGF on cell migration and proliferation, and the expression and subcellular dynamics of tight junction proteins; as well, we investigated the effect of HGF on paracellular permeability to macromolecules (using fluorescein isothiocyanate [FITC]-dextran). RESULTS: HGF significantly stimulated the migration of MKN74 cells, but not their proliferation, in a dose-dependent manner. HGF did not affect the expression of tight junction proteins, including claudin-1, -3, -4 and -7; occludin; and zonula occludens (ZO)-1. However, fluorescence immunostaining revealed that, in the cell membrane, the levels of ZO-1, but not those of occludin or claudin-4, were transiently decreased 1 h after HGF treatment. The results were further confirmed by western blotting: HGF reduced the amount of ZO-1 protein in the cell membrane fraction concomitantly with an increase in cytoplasmic ZO-1. Furthermore, HGF reduced the interaction between ZO-1 and occludin, and induced the tyrosine phosphorylation of occludin, whereas the phosphorylation status of ZO-1 was not affected by exposure to HGF. Despite a decrease in the ZO-1/occludin interaction, HGF did not affect paracellular permeability to macromolecules. CONCLUSIONS: HGF alters the subcellular localization of ZO-1, probably through the tyrosine phosphorylation of occludin, which may induce cell dispersion during epithelial restitution.
Assuntos
Mucosa Gástrica/efeitos dos fármacos , Fator de Crescimento de Hepatócito/farmacologia , Proteína da Zônula de Oclusão-1/metabolismo , Membrana Celular/metabolismo , Permeabilidade da Membrana Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Claudina-4/metabolismo , Citoplasma/metabolismo , Relação Dose-Resposta a Droga , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Mucosa Gástrica/citologia , Mucosa Gástrica/metabolismo , Fator de Crescimento de Hepatócito/administração & dosagem , Humanos , Ocludina/metabolismo , Fosforilação/efeitos dos fármacos , Células Tumorais CultivadasRESUMO
Hepatic steatosis (HS) has a negative effect on liver regeneration, but different pathophysiologies of HS may lead to different outcomes. Male Sprague-Dawley rats were fed a high fructose (66% fructose; H-fruc), high fat (54% fat; H-fat), or control chow diet for 4 weeks. Based on hepatic triglyceride content and oil red O staining, HS developed in the H-fruc group, but was less severe compared to the H-fat group. Hepatic mRNA expression levels of fatty acid synthase and fructokinase were increased and those of carnitine palmitoyltransferase-1 and peroxisome proliferator-activated receptor-α were decreased in the H-fruc group compared to the H-fat group. Liver regeneration after 70% partial hepatectomy (PHx) was evaluated by measuring the increase in postoperative liver mass and PCNA-positive hepatocytes, and was impaired in the H-fruc group compared to the H-fat and control groups on days 3 and 7. Serum levels of tumor necrosis factor-α, interleukin-6 and hepatocyte growth factor did not change significantly after PHx. In contrast, serum TGF-ß1 levels were slightly but significantly lower in the control group on day 1 and in the H-fat group on day 3 compared to the level in each group on day 0, and then gradually increased. However, the serum TGF-ß1 level did not change after PHx in the H-fruc group. These results indicate that impairment of liver regeneration after PHx in HS is related to the cause, rather than the degree, of steatosis. This difference may result from altered metabolic gene expression profiles and potential dysregulation of TGF-ß1 expression.