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A 70-year-old man undergoing treatment for immunoglobulin G4-related disease developed a liver mass on computed tomography during routine imaging examination. The tumor was located in the hepatic S1/4 region, was 38 mm in size, and showed arterial enhancement on dynamic contrast-enhanced computed tomography. We performed a liver biopsy and diagnosed moderately differentiated hepatocellular carcinoma. The patient underwent proton beam therapy. The tumor remained unchanged but enlarged after 4 years. The patient was diagnosed with hepatocellular carcinoma recurrence and received hepatic arterial chemoembolization. However, 1 year later, the patient developed jaundice, and the liver tumor grew in size. Unfortunately, the patient passed away. Autopsy revealed that the tumor consisted of spindle-shaped cells exhibiting nuclear atypia and a fission pattern and tested positive for α-smooth muscle actin and vimentin. No hepatocellular carcinoma components were observed, and the patient was pathologically diagnosed with hepatic leiomyosarcoma. Next-generation sequencing revealed somatic mutations in CACNA2D4, CTNNB1, DOCK5, IPO8, MTMR1, PABPC5, SEMA6D, and ZFP36L1. Based on the genetic mutation, sarcomatoid hepatocarcinoma was the most likely pathogenesis in this case. This mutation is indicative of the transition from sarcomatoid hepatocarcinoma to hepatic leiomyosarcoma.
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BACKGROUND: Given the increasing health concerns for patients with inflammatory bowel disease (IBD), amidst the COVID-19 pandemic, we investigated the impact of the pandemic on the anxiety and behavioral changes in Japanese patients with IBD. METHODS: We analyzed 3032 questionnaires from patients with IBD, aged 16 years or older visiting 30 hospitals and 1 clinic between March 2020 and June 2021. The primary outcome was the score of the anxiety experienced by patients with IBD during the pandemic. RESULTS: Participants reported a median age of 44 years; 43.3% of the patients were women. Moreover, 60.6% and 39.4% were diagnosed with ulcerative colitis and Crohn's disease, respectively, with a median disease duration of 10 years. Participants indicated an average of disease-related anxiety score of 5.1 ± 2.5 on a ten-point scale, with a tendency to increase, 1 month after the number of infected persons per population increased. The top three causes for anxiety were the risk of contracting COVID-19 during hospital visits, SARS-CoV-2 infection due to IBD, and infection by IBD medication. Factors associated with anxiety were gender (women), being a homemaker, hospital visit timings, mode of transportation (train), use of immunosuppressive drugs, and nutritional therapy. Most patients continued attending their scheduled hospital visits, taking their medications, experienced the need for a family doctor, and sought guidance and information regarding COVID-19 from primary doctors, television, and Internet news. CONCLUSIONS: Patients with IBD experienced moderate disease-related anxiety due to the pandemic and should be proactively informed about infectious diseases to relieve their anxiety.
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COVID-19 , Enfermedades Inflamatorias del Intestino , Adulto , Femenino , Humanos , Masculino , Ansiedad/epidemiología , Ansiedad/etiología , COVID-19/epidemiología , Pueblos del Este de Asia , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/epidemiología , Enfermedades Inflamatorias del Intestino/terapia , PandemiasRESUMEN
BACKGROUND: Human cytomegalovirus (HCMV) colitis can be involved in active ulcerative colitis (UC) in patients refractory to steroid and immunosuppressive drugs. Histological examination with colonic biopsy specimens and antigenemia assays are the standard tests for diagnosing HCMV enterocolitis, and we have previously reported the usefulness of mucosal polymerase chain reaction (PCR) methods. However, the associations among histopathological tests, antigenemia assays, and mucosal PCR are unknown. METHODS: We retrospectively analyzed 82 UC patients who underwent mucosal biopsy from inflamed colonic tissues for histological evaluation and mucosal PCR to detect HCMV. We analyzed the relationships between the HCMV-DNA copy number in colonic mucosa and other HCMV tests. RESULTS: In total, 131 HCMV mucosal PCR tests from 82 UC patients were positive. The HCMV-DNA copy number was significantly higher in patients with positive immunohistochemistry (IHC) (p < 0.01) and was correlated with the number of positive cells for the antigenemia (C7-HRP, p < 0.01; C10/11, p < 0.01). Receiver operating characteristic curve analysis confirmed 1300 copies/µg of HCMV-DNA as the best diagnostic cut-off value to predict positive results of antigenemia (area under the curve = 0.80, 95% CI 0.68-0.93). HCMV-DNA copy number also correlated with the total UCEIS score (p = 0.013) and the bleeding score (p = 0.014). For each individual patient, a positive correlation between the change in total UCEIS score and HCMV-DNA copy number was observed (p = 0.040). CONCLUSION: The antigenemia assay and histopathological test with IHC were significantly associated with the HCMV-DNA copy number in colonic tissues. Moreover, endoscopic examination with the UCEIS can help diagnose the HCMV colitis in UC patients.
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Colitis Ulcerosa , Infecciones por Citomegalovirus , Humanos , Colitis Ulcerosa/patología , Estudios Retrospectivos , Inmunohistoquímica , ADN Viral , Infecciones por Citomegalovirus/complicaciones , Infecciones por Citomegalovirus/diagnóstico , Citomegalovirus/genética , Reacción en Cadena de la Polimerasa/métodos , Mucosa Intestinal/patologíaRESUMEN
Immunoglobulin G4-related disease (IgG4-RD) is a systemic inflammatory disease characterized by the infiltration of IgG4-positive plasma cells and fibrosis in organs throughout the body. IgG4-RD involvement in the gastrointestinal (GI) tract (IgG4-related GI disease; IgG4-GID) is rare, and the disease concept remains unclear. Generally, IgG4-GID has been reported with morphological changes, including ulcers, strictures, and submucosal tumors. Here, we report a case of IgG4-GID with persistent diarrhea and abdominal pain in which typical endoscopic findings were absent. This case suggests the unidentified clinical features of IgG4-GID.
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We report a case in which multidisciplinary treatment was effective for hepatocellular carcinoma (HCC) with cranial and skeletal muscle metastases. A 55-year-old male with HCC received sorafenib for lung metastases. He was admitted to our hospital due to the skull metastasis detected by fluorodeoxyglucose positron emission tomography (FDG-PET). The patient underwent resection for skull metastasis. After the surgical treatment, he was treated with sorafenib again. Eight months after craniectomy, FDG-PET showed FDG uptake in the semimembranosus and semitendinosus muscles. Histopathological examination of the muscle biopsy revealed HCC muscle metastasis. Sorafenib treatment was discontinued. The investigational new drug (tegafur-gimeracil-oteracil) and tegafur-uracil were used for the treatment. These treatments proved to be ineffective as the lung metastases enlarged and new metastases appeared on the mediastinal lymph nodes and dura cava. The patient was unable to walk due to the enlarged thigh muscle metastases. Sorafenib was re-administered, which reduced the enlargement of the lung and mediastinal lymph nodes. Dural metastases were treated with resection and radiotherapy. Additional radiation therapy to the thigh muscles relieved the patient from pain experienced during walking. Sorafenib treatment was continued for the next 3 years. The patient survived for 4 years after the skull resection.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Neoplasias Pulmonares , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/terapia , Drogas en Investigación/uso terapéutico , Fluorodesoxiglucosa F18/uso terapéutico , Humanos , Neoplasias Hepáticas/patología , Neoplasias Pulmonares/secundario , Masculino , Persona de Mediana Edad , Músculo Esquelético/diagnóstico por imagen , Músculo Esquelético/patología , Cráneo/patología , Sorafenib/uso terapéutico , Tegafur/uso terapéuticoRESUMEN
Immunotherapy using anti-programmed death 1 ligand 1 (PD-L1) antibodies has shown clinical efficacy against hepatocellular carcinoma (HCC) and is recognized as the first-line treatment for unresectable HCC. PD-L1 expression is affected by various cytokines produced by immune cells in the tumor microenvironment; however, there is limited information about the effects of cytokine interactions on PD-L1 expression. In this study, we examined how cytokines induce PD-L1 expression in HCC cells. Both interferon gamma (IFN-γ) and interleukin 1 beta (IL-1ß) induced PD-L1 expression, and the two cytokines enhanced PD-L1 expression in combination compared to that when administered alone. The Janus kinase/signal transducer and activator of transcription signaling pathway activated by IFN-γ is the major pathway of PD-L1 expression. The increase in interferon regulatory factor 1 expression and IFN-γ receptor expression induced by IL-1ß was associated with the synergistic effect of IFN-γ and IL-1ß on PD-L1 expression. These findings strongly indicate that IFN-γ and IL-1ß affect the mechanism underlying immune resistance in HCC cells.
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Eosinophilic cholangiopathy (EC) presents with thickening and stenosis of the bile duct wall that is histologically characterized by eosinophil infiltration. The diagnosis is often difficult. We herein report a patient who had been followed up with a diagnosis of primary sclerosing cholangitis but had a final diagnosis of EC based on eosinophilia, histological findings of bile duct and liver biopsy specimens, and a review of a previous surgical specimen of the gallbladder. Antigen tests, isolation from her house, and accidental re-exposure to the antigen revealed that the causative antigen was the mite Dermatophagoides pteronyssinus.
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Colangitis Esclerosante , Colangitis , Eosinofilia , Hipersensibilidad , Ácaros , Animales , Conductos Biliares/patología , Colangitis/diagnóstico , Colangitis Esclerosante/diagnóstico , Colangitis Esclerosante/patología , Diagnóstico Diferencial , Eosinofilia/diagnóstico , Eosinofilia/patología , Femenino , HumanosRESUMEN
The number of patients with inflammatory bowel disease (IBD) is increasing worldwide. Endoscopy is the gold standard to assess the condition of IBD. The problem with this procedure is that the burden and cost on the patient are high. Therefore, the identification of a reliable biomarker to replace endoscopy is desired. Biomarkers are used in various situations such as diagnosis of IBD, evaluation of disease activity, prediction of therapeutic effect, and prediction of relapse. C-reactive protein and fecal calprotectin have a lot of evidence as objective biomarkers of disease activity in IBD. The usefulness of the fecal immunochemical test, serum leucine-rich glycoprotein, and urinary prostaglandin E major metabolite have also been reported. Herein, we comprehensively review the usefulness and limitations of biomarkers that can be used in daily clinical practice regarding IBD. To date, no biomarker is sufficiently accurate to replace endoscopy; however, it is important to understand the characteristics of each biomarker and use the appropriate biomarker at the right time in daily clinical practice.
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RATIONALE: Mixed neuroendocrine non-neuroendocrine neoplasm (MiNEN) is a rare tumor. MiNEN of the gallbladder (GB) with pancreaticobiliary maljunction (PMJ) is extremely rare. The origin of MiNEN of the GB remains unknown; the biliary tract normally lacks neuroendocrine cells. MiNEN of the GB has a poor prognosis; because of its rarity, no treatment or management guidelines have been established yet. PATIENT CONCERNS: A 47-year-old male presenting with right hypochondrial pain and malaise for 3 months was referred to our hospital for further management. DIAGNOSIS: The neuron-specific enolase level was increased. Contrast-enhanced computed tomography revealed a mass of 70âmm in size with unclear boundaries in the liver. The GB was surrounded by this mass, narrowing the lumen of the GB. Many swollen lymph nodes were observed in the hepatoduodenal ligament. Endoscopic retrograde cholangiopancreatography revealed a PMJ with a non-dilated biliary duct. A percutaneous biopsy was performed on the liver mass, and the pathological findings were neuroendocrine carcinoma (NEC) (small cell type). We diagnosed a NEC of the GB, T3N1M0, stage IIIB (Union for International Cancer Control, 7th edition). INTERVENTIONS: Because of advanced lymph node metastasis, we considered this tumor difficult to cure solely by surgical intervention. After initial chemotherapy consisting of cisplatin and irinotecan, a marked reduction in both tumor and lymph node sizes enabled conversion surgery. The pathological diagnosis of the resected tumor was MiNEN consisting of NEC and adenocarcinoma. The primary lesion was the adenocarcinoma occupying the luminal side of the GB. As a postsurgical treatment, the patient received additional irradiation therapy to the common hepatic duct and liver stump because of positive surgical margins. OUTCOMES: At 13âmonths postoperatively, computed tomography findings revealed the appearance of a hypervascular liver tumor, and laboratory data showed increased serum neuron-specific enolase levels. Chemotherapy was unsuccessful, leading to the death of the patient 36âmonths from the date of diagnosis. LESSONS: There are several reports on the development of MiNEN of the GB. In our case, a PMJ-related adenocarcinoma of the GB transdifferentiated into NEC. Further accumulation of cases is necessary to establish a treatment strategy for MiNEN of the GB.
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Neoplasias de la Vesícula Biliar/complicaciones , Tumores Neuroendocrinos/complicaciones , Mala Unión Pancreaticobiliar/complicaciones , Colangiopancreatografia Retrógrada Endoscópica , Neoplasias de la Vesícula Biliar/patología , Neoplasias de la Vesícula Biliar/terapia , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Tumores Neuroendocrinos/patología , Tumores Neuroendocrinos/terapia , Fosfopiruvato Hidratasa/sangreRESUMEN
Objective The change in serum lipid levels by direct-acting antiviral (DAA) treatment for chronic hepatitis C varies depending on the type of DAA. How the lipid level changes induced by glecaprevir-pibrentasvir (G/P) treatment contribute to the clinical outcome remains unclear. We conducted a prospective observational study to evaluate the effectiveness of G/P treatment and the lipid level changes. Methods The primary endpoint was a sustained virologic response at 12 weeks (SVR12). The total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels and LDL-C/HDL-C (L/H) ratio were measured every two weeks. Patients This study included 101 patients. Seventeen cases of liver cirrhosis and nine cases of DAA retreatment were registered. The G/P treatment period was 8 weeks in 74 cases and 12 weeks in 27 cases. Results SVR12 was evaluated in 96 patients. The rate of achievement of SVR12 in the evaluable cases was 100%. We found significantly elevated TC and LDL-C levels over the observation period compared to baseline. The serum levels of HDL-C did not change during treatment but were significantly increased after treatment compared to baseline. The L/H ratio was significantly increased two weeks after the start of treatment but returned to the baseline after treatment. Conclusion The primary endpoint of the SVR12 achievement rate was 100%. G/P treatment changed the serum lipid levels. Specifically, the TC and LDL-C levels increased during and after treatment, and the HDL-C levels increased after treatment. G/P treatment may be associated with a reduced thrombotic risk. Therefore, validation in large trials is recommended.
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Antivirales , Hepatitis C Crónica , Ácidos Aminoisobutíricos , Antivirales/uso terapéutico , Bencimidazoles , HDL-Colesterol , LDL-Colesterol , Ciclopropanos , Genotipo , Hepacivirus , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Lactamas Macrocíclicas , Leucina/análogos & derivados , Prolina/análogos & derivados , Pirrolidinas , Quinoxalinas , SulfonamidasRESUMEN
Familial Mediterranean fever (FMF) in gastrointestinal involvement has been considered rare, but resent reports suggest that FMF causes enterocolitis which is similar endoscopic findings to inflammatory bowel disease. The clinical characteristics and endoscopic findings of FMF with enterocolitis remain unclear. Here, we report a case of an FMF patient who had enterocolitis with stricture of the terminal ileum whose endoscopic and clinical features mimicked Crohn's disease. A 23-year-old man who was diagnosed with FMF 10 years ago presented with abdominal pain and diarrhea. Colonoscopy showed terminal ileitis and aphthous colitis; however, these findings, including the histopathology, did not confirm Crohn's disease. Therefore, we diagnosed FMF with enterocolitis and administered anti-interleukin-1ß monoclonal antibody (canakinumab). The patient's symptoms improved with treatment, but after 1 year, lower abdominal pain recurred. Colonoscopy revealed a stricture of the terminal ileum. Endoscopic balloon dilation relieved his symptoms. At present, he has been followed up without surgical treatment by endoscopic balloon dilation every 6 month. Clinicians should be aware that FMF accompanied with enterocolitis may resemble Crohn's disease.
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Colitis , Enfermedad de Crohn , Fiebre Mediterránea Familiar , Dolor Abdominal , Adulto , Colonoscopía , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/diagnóstico , Fiebre Mediterránea Familiar/complicaciones , Fiebre Mediterránea Familiar/diagnóstico , Humanos , Masculino , Adulto JovenRESUMEN
Although primarily a respiratory illness, several studies have shown that COVID-19 causes elevation of liver enzymes and various gastrointestinal (GI) symptoms. The aim of this study was to undertake a systematic review and meta-analysis to determine whether the presence of gastrointestinal (GI) symptoms contributed toward COVID-19 severity, and identify the GI symptoms characteristic of severe COVID-19. We conducted a literature search of PubMed from December 1, 2019, to June 30, 2020, and identified all reports with GI symptoms reported. A meta-analysis comparing the severity of COVID-19 with the presence of liver enzyme elevation and GI symptoms was performed using RevMan version 5.4. Pooled data from 15,305 unique reverse transcriptase-polymerase chain reaction positive COVID-19 patients from 44 studies were analyzed. We found that the severe COVID-19 patients significantly had abdominal pain compared to the non-severe COVID-19 patients (OR = 2.70, 95% CI 1.17-6.27, Z = 2.32, p = 0.02, I2 = 0%) by analyzed 609 patients of 4 studies who reported both abdominal pain and COVID-19 severity. However, there was no significant difference in the incidence of diarrhea, nausea, or vomiting between the two groups. Thus, this systematic review and meta-analysis demonstrated that abdominal pain could be characteristic of severe COVID-19 infections. Compared with other viral infections that primarily infect the respiratory system, patients with COVID-19 have a slightly lower frequency of diarrheal symptoms with abdominal pain. However, to confirm this, further studies with COVID-19 patients across various countries and ethnicities are required.
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COVID-19/complicaciones , Enfermedades Gastrointestinales/epidemiología , Hígado/enzimología , Dolor Abdominal/etiología , COVID-19/fisiopatología , Diarrea/epidemiología , Diarrea/virología , Enfermedades Gastrointestinales/virología , Humanos , Hígado/virología , Náusea/epidemiología , Náusea/virología , Índice de Severidad de la Enfermedad , Vómitos/epidemiología , Vómitos/virologíaRESUMEN
We demonstrate a case, in which endoscopic ultrasonography-guided fine-needle biopsy (EUS-FNB) was useful for determining the diagnosis of lesions of retroperitoneal fibrosis. In our case, accessing the retroperitoneal lesions by conventional percutaneous biopsy procedures was not feasible due to the difficulty of avoiding the inferior vena cava and ureter. We believe that our case demonstrates a unique approach for performing histological analysis in a challenging case.
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The relevance of endoscopic monitoring of ulcerative colitis (UC) has been translated into the new concept of "mucosal healing (MH)" as the therapeutic goal to achieve because a large amount of scientific data have revealed the favorable prognostic value of a healed mucosa in determining the clinical outcome of UC. Recent interest in MH has skewed toward not only endoscopic remission but also histological improvement (so called histological MH). However, we should recognize that there have been no prospectively validated endoscopic scoring systems of UC activity in previous clinical trials. Artificial intelligence (AI)-assisted endoscopy has been developed for gastrointestinal cancer surveillance. Recently, several AI-assisted endoscopic systems have been developed for assessment of MH in UC. In the future, the development of a new endoscopic scoring system based on AI might standardize the definition of MH. Therefore, "The road to an exact definition of MH in the treatment of UC has begun only now".
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Colitis Ulcerosa , Inteligencia Artificial , Colitis Ulcerosa/diagnóstico por imagen , Colonoscopía , Endoscopía , Humanos , Mucosa Intestinal , Índice de Severidad de la Enfermedad , Cicatrización de HeridasRESUMEN
Autophagy refers to the process involving the decomposition of intracellular components via lysosomes. Autophagy plays an important role in maintaining and regulating cell homeostasis by degrading intracellular components and providing degradation products to cells. In vivo, autophagy has been shown to be involved in the starvation response, intracellular quality control, early development, and cell differentiation. Recent studies have revealed that autophagy dysfunction is implicated in neurodegenerative diseases and tumorigenesis. In addition to the discovery of certain disease-causing autophagy-related mutations and elucidation of the pathogenesis of conditions resulting from the abnormal degradation of selective autophagy substrates, the activation of autophagy is essential for prolonging life and suppressing aging. This article provides a comprehensive review of the role of autophagy in health, physiological function, and autophagy-related disease.
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Autofagia , Enfermedad , Animales , Salud , Humanos , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Modelos BiológicosRESUMEN
The inflammasome is an intracellular molecular complex, which is mainly involved in innate immunity. Inflammasomes are formed in response to danger signals, associated with infection and injury, and mainly regulate the secretion of interleukin-1ß and interleukin-18. Inflammasome dysregulation is known to be associated with various diseases and conditions, and its regulatory mechanisms have become of great interest in recent years. In the colon, inflammasomes have been reported to be associated with autophagy and the microbiota, and their dysregulation contributes to colitis and. However, the detailed role of inflammasomes in inflammatory bowel disease is still under debate because the mechanisms that regulate the inflammasome are complex and the inflammasome components and cytokines show seemingly contradictory multiple effects. Herein, we comprehensively review the literature on inflammasome functioning in the colon and describe the complex interactions of the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome components with inflammatory cytokines, autophagy, and the microbiota in experimental colitis models and patients with inflammatory bowel disease.
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Colitis/inmunología , Colitis/patología , Inflamasomas/inmunología , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Animales , Colitis/metabolismo , Humanos , Inflamasomas/metabolismoRESUMEN
Patients with chronic inflammatory bowel diseases are at an increased risk of developing colitis-associated cancer (CAC). Chronic inflammation positively correlates with tumorigenesis. Similarly, the cumulative rate of incidence of developing CAC increases with prolonged colon inflammation. Immune signaling pathways, such as nuclear factor (NF)-κB, prostaglandin E2 (PGE2)/cyclooxygenase-2 (COX-2), interleukin (IL)-6/signal transducer and activator of transcription 3 (STAT3), and IL-23/T helper 17 cell (Th17), have been shown to promote CAC tumorigenesis. In addition, gut microbiota contributes to the development and progression of CAC. This review summarizes the signaling pathways involved in the pathogenesis following colon inflammation to understand the underlying molecular mechanisms in CAC tumorigenesis.
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Neoplasias del Colon/inmunología , Disbiosis/complicaciones , Enfermedades Inflamatorias del Intestino/complicaciones , Animales , Neoplasias del Colon/etiología , Ciclooxigenasa 2/metabolismo , Citocinas/metabolismo , Progresión de la Enfermedad , Disbiosis/inmunología , Microbioma Gastrointestinal , Humanos , Enfermedades Inflamatorias del Intestino/inmunología , Factor de Transcripción STAT3/metabolismo , Transducción de Señal , Células Th17/metabolismoRESUMEN
Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus (the human herpesvirus 5) and an opportunistic pathogen that primarily infects HIV-positive and other immuno-compromised patients. Retrospective studies in the field of inflammatory bowel disease (IBD) have suggested a relationship between a concomitant colonic HCMV infection and poor outcomes in patients with an ulcerative colitis (UC) due to the presence of HCMV in surgical specimens of patients with a toxic megacolon or a steroid-resistant UC. Therefore, gastroenterologists have focused on the contribution of HCMV infections in the exacerbation of UC. Numerous studies have addressed the benefits of treating colonic HCMV reactivation in UC using an antiviral treatment. However, its clinical relevance remains uncertain as only a few prospective studies have assessed the direct relationship between clinical outcomes and the viral load of HCMV in colonic tissues. HCMV reactivation can be triggered by inflammation according to fundamental research studies. Thus, optimal control of intestinal inflammation is essential for preventing an HCMV reactivation in the intestinal mucosa. Indeed, several reports have indicated the effectiveness of an anti-tumor necrosis factor-alpha (TNFα) treatment in patients with an active UC and concomitant HCMV infections. In this review, we describe the mechanism of HCMV reactivation in UC cases and discuss the current issues regarding diagnosis and treatment of HCMV infections in UC patients.