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1.
Esophagus ; 20(2): 256-263, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36456753

RESUMEN

BACKGROUND: Endoscopic submucosal dissection (ESD) is a minimally invasive treatment for pharyngeal cancers. However, pharyngeal ESD is sometimes technically challenging because of the narrow and complex space in which to work. Traction is important to complete the procedure efficiently. Here, we report the technical details and efficacy of a new traction method for pharyngeal ESD using ring-shaped thread and grasping forceps. METHODS: We analyzed pharyngeal ESD performed between January 2016 and March 2021 at our Institute. We designated cases resected using ring-shaped threads "Group R" and those resected without ring-shaped threads as conventional "Group C", and compared the technical outcomes between them. Multivariate analysis and the inverse probability treatment weighting (IPTW) method using propensity scores were adjusted by confounding variables. RESULTS: We analyzed 89 lesions from 68 patients, of which 46 were in Group R and 43 in Group C. Median procedure time and median dissection speed were significantly shorter in Group R than C (37 min vs. 55 min, and 16.0 mm2/min vs. 7.0 mm2/min, respectively, both P < 0.05). These results were confirmed by both multivariate analysis and after IPTW adjustment. All lesions were resected en bloc, and the complete resection rate was not significantly different between Group R and C (91.3% vs. 79.1%, P = 0.14). There were no treatment-related adverse events in either group. CONCLUSIONS: The traction method using ring-shaped thread increases the efficiency of pharyngeal ESD. This simple new traction method should be a useful option for pharyngeal ESD.


Asunto(s)
Resección Endoscópica de la Mucosa , Tracción , Humanos , Resultado del Tratamiento , Resección Endoscópica de la Mucosa/efectos adversos , Resección Endoscópica de la Mucosa/métodos , Faringe/cirugía , Instrumentos Quirúrgicos
2.
Int J Clin Oncol ; 26(5): 922-932, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33730200

RESUMEN

BACKGROUND: Our aim is to evaluate the utility of liver function measured by modified albumin-bilirubin (mALBI) grade to predict eligibility for second-line therapies, including regorafenib and ramucirumab therapy, at initiation of sorafenib therapy for patients with hepatocellular carcinoma (HCC). METHODS: Participants in this retrospective, single-center study comprised 197 patients with sorafenib-treated HCC, Child-Pugh scores (CPs) 5-7 and performance status 0-1 treated between October 2009 and June 2019. The factors at initiation of sorafenib therapy, including mALBI grade and CPs, were analyzed with regard to second-line eligibility, regorafenib eligibility and ramucirumab eligibility, respectively. RESULTS: Proportions of eligibility for second-line therapies, regorafenib therapy and ramucirumab therapy were 48.7%, 35.5% and 18.3%. Modified ALBI grades 1 and 2a were contributing factors for second-line eligibility (odd ratios [OR] 16.7 and 5.6; 95% CI 6.5-43.3 and 2.6-12.2), regorafenib therapy (OR 13.9 and 6.9; 95% CI 5.6-34.4 and 2.9-16.2), and ramucirumab therapy (OR 9.5 and 4.8; 95% CI 2.9-30.8 and 1.6-14.4), with grade 2b defined as reference. Patients with mALBI grade 1 and CPs 5 exhibited especially high proportion of eligibility for regorafenib therapy (70.5%). In patients with mALBI grade 2b, those with CPs 5 displayed higher proportion of eligibility for second-line therapy and ramucirumab therapy (100% and 50%) than those with CPs 6 (31.8% and 11.4%). CONCLUSIONS: Modified ALBI grade in combination with CPs at the initiation of sorafenib therapy would be useful to predict eligibility for second-line therapies.

3.
BMC Gastroenterol ; 20(1): 371, 2020 Nov 09.
Artículo en Inglés | MEDLINE | ID: mdl-33167879

RESUMEN

BACKGROUND: Sarcopenia is a syndrome characterized by progressive and systemic decreases in skeletal muscle mass and muscle strength. The influence or prognosis of various liver diseases in this condition have been widely investigated, but little is known about whether sarcopenia and/or muscle mass loss are related to minimal hepatic encephalopathy (MHE). METHODS: To clarify the relationship between MHE and sarcopenia and/or muscle mass loss in patients with liver cirrhosis. METHODS: Ninety-nine patients with liver cirrhosis were enrolled. MHE was diagnosed by a neuropsychiatric test. Skeletal mass index (SMI) and Psoas muscle index (PMI) were calculated by dividing skeletal muscle area and psoas muscle area at the third lumbar vertebra by the square of height in meters, respectively, to evaluate muscle volume. RESULTS: This study enrolled 99 patients (61 males, 38 females). MHE was detected in 48 cases (48.5%) and sarcopenia in 6 cases (6.1%). Patients were divided into two groups, with or without MHE. Comparing groups, no significant differences were seen in serum ammonia concentration or rate of sarcopenia. SMI was smaller in patients with MHE (46.4 cm2/m2) than in those without (51.2 cm2/m2, P = 0.027). Similarly, PMI was smaller in patients with MHE (4.24 cm2/m2) than in those without (5.53 cm2/m2, P = 0.003). Skeletal muscle volume, which is represented by SMI or PMI was a predictive factor related to MHE (SMI ≥ 50 cm2/m2; odds ratio 0.300, P = 0.002, PMI ≥ 4.3 cm2/m2; odds ratio 0.192, P = 0.001). CONCLUSIONS: Muscle mass loss was related to minimal hepatic encephalopathy, although sarcopenia was not. Measurement of muscle mass loss might be useful to predict MHE.


Asunto(s)
Carcinoma Hepatocelular , Encefalopatía Hepática , Neoplasias Hepáticas , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/patología , Estudios de Casos y Controles , Femenino , Encefalopatía Hepática/epidemiología , Humanos , Incidencia , Cirrosis Hepática/complicaciones , Cirrosis Hepática/epidemiología , Cirrosis Hepática/patología , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Músculo Esquelético/patología
4.
Dig Endosc ; 32(1): 106-113, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31429986

RESUMEN

BACKGROUND AND AIM: In Japan, risk stratification after baseline colonoscopy is not widely accepted. We investigated the findings of baseline colonoscopies at 17 community practices and evaluated the risk of the incidence of advanced neoplasia over a 5-year period. METHODS: This retrospective cohort study enrolled 3115 subjects over 40 years of age who underwent baseline colonoscopies and had at least one repeated colonoscopy within 5 years. Each group was classified based on the endoscopic findings of the baseline colonoscopy: no neoplasia/diminutive polyp <5 mm (N/D); small adenoma <10 mm; advanced adenoma; invasive cancer, respectively. We examined the incidence of advanced neoplasia during these 5 years and investigated the relationship between the surveillance colonoscopy and newly detected advanced neoplasia. RESULTS: The small adenoma group did not show any significant increased risk as compared to the N/D group (hazard ratio [HR]: 0.799. 95% CI 0.442-1.443). There was a significantly increased risk in the advanced adenoma and invasive cancer groups (HR: 4.996, 95% CI 2.940-8.491, HR: 3.737, 95% CI 1.309-10.666). Cancer incidences during the study period were 0.18% in the N/D group, and 1.9% in the invasive cancer group, respectively. Undergoing surveillance colonoscopies twice within 5 years decreased the risk of advanced neoplasia. CONCLUSIONS: There was a close relationship between the endoscopic findings of baseline colonoscopies and subsequent advanced neoplasia development. Risk stratification for advanced neoplasia based on the baseline findings can serve as a useful index for determining the optimal interval and frequency of colonoscopies over a 5-year period.


Asunto(s)
Colonoscopía/estadística & datos numéricos , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/epidemiología , Lesiones Precancerosas/diagnóstico , Lesiones Precancerosas/epidemiología , Adenoma/diagnóstico , Adenoma/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Pólipos del Colon/diagnóstico , Pólipos del Colon/epidemiología , Femenino , Humanos , Incidencia , Japón/epidemiología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo
6.
In Vivo ; 38(3): 1465-1469, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38688629

RESUMEN

BACKGROUND/AIM: The long-term use of proton pump inhibitors (PPIs) has been reported to be strongly associated with the development of fundic gland polyps (FGPs). Conversely, a few cases of gastric hyperplastic polyps (GHPs) associated with PPI use have been reported. We experienced a case of PPI-associated multiple GHPs with uncontrollable bleeding. CASE REPORT: A 64 year old man with a history of rheumatoid arthritis presented to the hospital with complaints of vertigo and black stools. Blood tests revealed anemia and hypoproteinemia. Esophagogastroduodenoscopy (EGD) showed blood and black residue accumulated in the stomach. The source of the bleeding was multiple hyperplastic polyps. Bleeding could be stopped even with fasting, and total blood transfusions amounted to 28 units of RBCs were required in 18 days. After the cessation of PPI, EGD showed that the polyps had almost disappeared. Pathological diagnosis of resected polyp was hyperplastic polyp, which was characterized by capillary hyperplasia and edema. Gastrin receptors were over-expressed in the foveolar epithelium and not in the capillaries. Methotrexate (MTX)-induced portal hypertensive gastroenteropathy was revealed during follow-up. We consider that the effect of portal hypertension may have caused the capillary hyperplasia. CONCLUSION: Although PPI-related polyps are usually fundic gland polyps and do not cause life-threatening adverse events, we experienced PPI-related GHPs in which hemostasis was difficult to control.


Asunto(s)
Pólipos Adenomatosos , Inhibidores de la Bomba de Protones , Humanos , Masculino , Inhibidores de la Bomba de Protones/efectos adversos , Persona de Mediana Edad , Hiperplasia , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/inducido químicamente , Hemorragia Gastrointestinal/diagnóstico , Neoplasias Gástricas/complicaciones , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Neoplasias Gástricas/diagnóstico , Pólipos/patología , Pólipos/diagnóstico , Pólipos/inducido químicamente , Endoscopía del Sistema Digestivo
7.
Clin J Gastroenterol ; 17(2): 244-252, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38193986

RESUMEN

BACKGROUND: Chronic intestinal pseudo-obstruction (CIPO) is a rare intestinal disorder characterized by impaired propulsion of the digestive tract and associated with symptoms of intestinal obstruction, despite the absence of obstructive lesions. CIPO includes several diseases. However, definitive diagnosis of its etiology is difficult only with symptoms or imaging findings. CASE PRESENTATION: A 56-year-old man was referred to our hospital due to a 3-year history of continuous abdominal distention. Imaging, including computed tomography of the abdomen, and endoscopy revealed marked dilatation of the entire small intestine without any obstruction point. Therefore, he was diagnosed with CIPO. Since medical therapy didn't improve his symptoms, enterostomy and percutaneous endoscopic gastro-jejunostomy were performed. These procedures improved abdominal symptoms. However, he required home central venous nutrition due to dehydration. The pathological findings of full-thickness biopsies of the small intestine taken during surgery revealed decreased number and degeneration of ganglion cells in the normal plexus. These findings led to a final diagnosis of CIPO due to acquired isolated hypoganglionosis (AIHG). CONCLUSIONS: Here, we report the case of a patient with CIPO secondary to adult-onset AIHG of the small intestine. Since AIHG cannot be solely diagnosed using clinical findings, biopsy is important for its diagnosis.


Asunto(s)
Obstrucción Intestinal , Seudoobstrucción Intestinal , Masculino , Adulto , Humanos , Persona de Mediana Edad , Seudoobstrucción Intestinal/etiología , Seudoobstrucción Intestinal/cirugía , Seudoobstrucción Intestinal/diagnóstico , Dilatación Patológica , Atrofia Muscular , Intestino Delgado/cirugía , Enfermedad Crónica
8.
Biochem Biophys Res Commun ; 430(2): 757-62, 2013 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-23206702

RESUMEN

Differentiation of placental trophoblast stem (TS) cells to trophoblast giant (TG) cells is accompanied by transition from a mitotic cell cycle to an endocycle. Here, we report that Cdh1, a regulator of the anaphase-promoting complex/cyclosome (APC/C), negatively regulates mitotic entry upon the mitotic/endocycle transition. TS cells derived from homozygous Cdh1 gene-trapped (Cdh1(GT/GT)) murine embryos accumulated mitotic cyclins and precociously entered mitosis after induction of TS cell differentiation, indicating that Cdh1 is required for the switch from mitosis to the endocycle. Furthermore, the Cdh1(GT/GT) TS cells and placenta showed aberrant expression of placental differentiation markers. These data highlight an important role of Cdh1 in the G2/M transition during placental differentiation.


Asunto(s)
Proteínas de Ciclo Celular/fisiología , Diferenciación Celular/fisiología , Puntos de Control de la Fase G2 del Ciclo Celular/fisiología , Células Madre/citología , Trofoblastos/citología , Complejos de Ubiquitina-Proteína Ligasa/metabolismo , Ciclosoma-Complejo Promotor de la Anafase , Animales , Proteínas Cdh1 , Proteínas de Ciclo Celular/genética , Diferenciación Celular/genética , Femenino , Puntos de Control de la Fase G2 del Ciclo Celular/genética , Puntos de Control de la Fase M del Ciclo Celular/genética , Puntos de Control de la Fase M del Ciclo Celular/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Placenta/citología , Embarazo
9.
DEN Open ; 3(1): e163, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36176350

RESUMEN

Objectives: Endoscopic submucosal resection with band ligation (ESMR-L) and endoscopic submucosal dissection (ESD) are both standard endoscopic resection methods for rectal neuroendocrine tumors (NETs) <10 mm in size. However, there is no definitive consensus on which is better. Here, we compared the efficacy of ESMR-L and ESD for small rectal NETs. Methods: This was a multicenter retrospective cohort study including 205 patients with rectal NETs who underwent ESMR-L or ESD. Treatment outcomes were compared by univariate analysis, multivariate analysis, and inverse probability treatment weighting (IPTW) using propensity scores. Subgroup analysis evaluated the impact of the endoscopist's experience on the technical outcome. Results: Eighty-nine patients were treated by ESMR-L and 116 by ESD. The R0 resection rate was not significantly different between the two (90% vs. 92%, p = 0.73). The procedure time of ESMR-L was significantly shorter than for ESD (17 min vs. 52 min, p < 0.01) and the hospitalization period was also significantly shorter (3 days vs. 5 days, p < 0.01). These results were confirmed by multivariate analysis and also after IPTW adjustment. The procedure time of ESD was significantly prolonged by a less-experienced endoscopist (49 min vs. 70 min, p = 0.02), but that of ESMR-L was not affected (17 min vs. 17 min, p = 0.27). Conclusions: For small rectal NETs, both ESMR-L and ESD showed similar high complete resection rates. However, considering the shorter procedure time and shorter hospitalization period, ESMR-L is the more efficient treatment method, especially for less-experienced endoscopists.

10.
J Clin Med ; 12(9)2023 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-37176572

RESUMEN

BACKGROUND: Mediterranean fever (MEFV) gene mutations are responsible for familial Mediterranean fever (FMF) and associated with other inflammatory diseases. However, the effects of MEFV gene mutations on intestinal Behçet's disease (BD) are unknown. In this study, we investigated these mutations and clinical features in patients with intestinal BD. METHODS: MEFV gene analysis was performed in 16 patients with intestinal BD, 10 with BD without intestinal lesions, and 50 healthy controls. Clinical features of patients with intestinal BD were retrospectively assessed. RESULTS: The rates of MEFV gene mutations in patients with intestinal BD, BD without intestinal lesions, and healthy controls were 75%, 50%, and 38%, respectively. Only 2 of 12 patients with intestinal BD harboring MEFV gene mutations (17%) were controlled without immunosuppressive treatment, while 8 patients (67%) required therapy with tumor necrosis factor (TNF) inhibitors. Among patients with intestinal BD without MEFV gene mutations (four patients), three (75%) were controlled by the administration of 5-aminosalicylic acid with or without colchicine, and one (25%) required TNF inhibitors. All patients who underwent intestinal resection had MEFV gene mutations. Immunohistochemical analysis and in situ hybridization with interleukin-1ß (IL-1ß) showed a high expression of IL-1ß only in injured areas, suggesting that IL-1ß may be involved in the formation of ulcers in patients with intestinal BD carrying MEFV gene mutations. CONCLUSION: Mutations in the MEFV gene may be associated with intestinal lesions of BD and refractoriness to treatment.

11.
Am J Pathol ; 179(3): 1471-82, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21787741

RESUMEN

Gestational choriocarcinoma is a malignant trophoblastic tumor. The development of novel molecular-targeted therapies is needed to reduce the toxicity of current multiagent chemotherapy and to treat successfully the chemoresistant cases. The molecular mechanisms underlying choriocarcinoma tumorigenesis remain uncharacterized, however, and appropriate choriocarcinoma animal models have not yet been developed. In this study, we established a choriocarcinoma model by inoculating mice with induced-choriocarcinoma cell-1 (iC³-1) cells, generated from HTR8/SVneo human trophoblastic cells retrovirally transduced with activated H-RAS (HRASV12). The iC³-1 cells exhibited constitutive activation of the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) pathways and developed into lethal tumors in all inoculated mice. Histopathological analysis revealed that the tumors consisted of two distinct types of cells, reminiscent of syncytiotrophoblasts and cytotrophoblasts, as seen in the human choriocarcinoma. The tumors expressed HLA-G and cytokeratin (trophoblast markers) and hCG (a choriocarcinoma marker). Comparative analysis of gene expression profiles between iC³-1 cells and parental HTR8/SVneo cells revealed that iC³-1 cells expressed matrix metalloproteinases, epithelial-mesenchymal transition-related genes, and SOX3 at higher levels than parental trophoblastic cells. Administration of SOX3-specific short-hairpin RNA decreased SOX3 expression and attenuated the tumorigenic activity of iC³-1 cells, suggesting that SOX3 overexpression might be critically involved in the pathogenesis of choriocarcinoma. Our murine model represents a potent new tool for studying the pathogenesis and treatment of choriocarcinoma.


Asunto(s)
Coriocarcinoma/etiología , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Neoplasias Uterinas/etiología , Animales , Línea Celular Tumoral , Transformación Celular Neoplásica , Coriocarcinoma/metabolismo , Femenino , Humanos , Ratones , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Trasplante de Neoplasias , Fosfatidilinositol 3-Quinasas/metabolismo , Embarazo , Factores de Transcripción SOXB1/metabolismo , Transducción Genética , Trasplante Heterólogo , Neoplasias Uterinas/metabolismo
12.
Nihon Shokakibyo Gakkai Zasshi ; 109(7): 1236-42, 2012 Jul.
Artículo en Japonés | MEDLINE | ID: mdl-22790629

RESUMEN

A 29-year-old pregnant woman was referred to our hospital with suspected acute pancreatitis. On admission, the serum levels of pancreatic enzyme, total cholesterol and triglyceride were markedly elevated, which suggesting acute pancreatitis with hyperlipidemia. Treatment consisted of continuous hemodiafiltration, LDL apheresis, heparin and insulin combination therapy. On the 24th day of hospitalization, a cesarean section delivery resulted in the birth of a healthy infant. We reported a case of hyperlipidemia-induced acute pancreatitis in a woman with second trimester pregnancy, where multidisciplinary treatment was quite effective.


Asunto(s)
Hiperlipidemias/complicaciones , Pancreatitis/etiología , Complicaciones del Embarazo , Enfermedad Aguda , Adulto , Cesárea , Femenino , Humanos , Hiperlipidemias/terapia , Recién Nacido , Masculino , Pancreatitis/terapia , Embarazo
13.
Case Rep Gastroenterol ; 16(3): 637-645, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36605731

RESUMEN

Esophageal neuroendocrine neoplasms are extremely rare, and their prognosis is poor. Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) are even more rare and are defined as tumors consisting of neuroendocrine carcinoma and either adenocarcinoma or squamous cell carcinoma. We report a rare case featuring endoscopic submucosal dissection (ESD) for an esophageal MiNEN, arising from the ectopic gastric mucosa in the lower thoracic esophagus. A 92-year-old male patient was referred to this hospital for investigation of an esophageal tumor. An endoscopic examination revealed a 10 mm elevated lesion, with 8 mm flat areas on the anal side, within the ectopic gastric mucosa located in the lower thoracic esophagus. ESD was carried out, and a histopathological examination revealed a tubular adenocarcinoma composed of differentiated neuroendocrine cells. Immunohistochemical staining was positive for synaptophysin and negative for chromogranin A. The labeling index of Ki-67 was more than 80%. Based on these results, we diagnosed the lesion as an esophageal MiNEN, arising in the ectopic gastric mucosa of the esophagus. The patient remains alive, without recurrence of cancer, 24 months after ESD.

14.
Hepatol Commun ; 6(5): 1198-1212, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-34837478

RESUMEN

Advanced hepatocellular carcinoma (HCC) remains a highly lethal malignancy, although several systemic therapeutic options are available, including sorafenib (SFN), which has been one of the standard treatment agents for almost a decade. As early prediction of response to SFN remains challenging, biomarkers that enable early prediction using a clinically feasible method are needed. Here, we report that the serum secretory form of clusterin (sCLU) protein and its related predictive index are potential beneficial biomarkers for early prediction of SFN response. Using high-throughput screening and subsequent multivariate analysis in the derivation cohort, we found that changes in the concentrations of CLU, vascular cell adhesion molecule-1 (VCAM1), and α-fetoprotein were significantly associated with response to SFN. Furthermore, we confirmed that an increase in CLU serum level 1 month after treatment initiation was significantly associated with shorter progression-free survival. In addition, "NR-index," which comprises these proteins, was evaluated as a tool for accurately predicting the efficacy of SFN and confirmed in the validation cohort. We also established SFN-resistant HepG2 cells (HepG2-SR) and found that sCLU significantly increased in HepG2-SR cells compared with normal HepG2 cells, and confirmed that HepG2-SR cells treated with SFN were resistant to apoptosis. The mechanism underlying activation of sCLU expression in acquired SFN resistance involves aberrant signaling and expression of Akt, mammalian target of rapamycin (mTOR), and a nutrient-related transcription factor, sterol regulatory element binding protein 1c (SREBP-1c). Furthermore, the PI3K and mTOR inhibitor BEZ235 markedly decreased sCLU expression in HepG2-SR cells. Conclusion: These results suggest that measurement of sCLU serum levels and the sCLU-related NR-index are promising clinical tools for the early prediction of SFN response in HCC. Additionally, sCLU-overexpressing HCC might be susceptible to mTOR inhibition.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Biomarcadores , Carcinoma Hepatocelular/tratamiento farmacológico , Clusterina/metabolismo , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Sorafenib/farmacología , Serina-Treonina Quinasas TOR/uso terapéutico
15.
Cancer Sci ; 102(5): 967-74, 2011 May.
Artículo en Inglés | MEDLINE | ID: mdl-21255192

RESUMEN

Various key cell cycle components, especially G0/G1 regulators, have effects not only on cell proliferation but also on cell differentiation. Cdh1, one of the co-activators that maintain anaphase-promoting complex/cyclosome activity, plays a crucial role in the mitotic phase, but has recently been identified as a G0/G1 regulator, suggesting that the role of Cdh1 in cell differentiation. Here, we generated Cdh1 conditional gene-trap mice to examine Cdh1 functions in adult tissues by overcoming the embryonic lethality of Cdh1 homozygous gene-trap mice. We focused on the hematopoietic system and found that Cdh1-deficient mice exhibited a general decrease in mature lineage progenitor cells and a significant increase in short-term hematopoietic stem cells. This phenomenon became conspicuous by irradiation shortly after Cdh1 downregulation, suggesting that Cdh1 regulates the pool sizes of the hematopoietic stem cells and mature lineage progenitor cells by protecting cells from genotoxic stress. We also found that the irradiation-induced G2/M checkpoint was defective in Cdh1-deficient BM cells, causing the loss of stem/progenitor cells. This is the first report revealing Cdh1 function in adult hematopoiesis and showing a role of Cdh1 in a G2/M checkpoint regulation in vivo.


Asunto(s)
Proteínas de Ciclo Celular/metabolismo , Diferenciación Celular , Linaje de la Célula , Hematopoyesis/fisiología , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/metabolismo , Animales , Proteínas Cdh1 , Proteínas de Ciclo Celular/genética , División Celular , Fase G2 , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , ARN Mensajero/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
16.
PLoS One ; 16(1): e0245211, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33481809

RESUMEN

Risk stratification by index colonoscopy is well established for first surveillance endoscopy, but whether the previous two colonoscopies affect the subsequent advanced neoplasias has not been established. Therefore, the subsequent risk based on the findings of the index and first surveillance colonoscopies were investigated. This retrospective, cohort study was conducted in two clinics and included participants who had undergone two or more colonoscopies after index colonoscopy. High-risk was defined as advanced adenoma (≥ 1 cm, or tubulovillous or villous histology, or high-grade dysplasia). Based on the findings of the index and first surveillance colonoscopies, patients were classified into four categories: category A (both colonoscopy findings were normal), category B (no high-risk findings both times), category C (one time high-risk finding), and category D (high-risk findings both times). The incidence of subsequent advanced neoplasia was examined in each category. A total of 13,426 subjects were included and surveyed during the study periods. The subjects in category D had the highest risk of advanced neoplasia (27.4%, n = 32/117). The subjects in category A had the lowest risk (4.0%, n = 225/5,583). The hazard ratio for advanced neoplasia of category D compared to category A was 9.90 (95% Confidence interval 6.82-14.35, P<0.001). Classification based on the findings of index and first surveillance colonoscopies more effectively stratifies the risk of subsequent advanced neoplasia, resulting in more proper allocation of colonoscopy resources after two consecutive colonoscopies.


Asunto(s)
Adenoma/diagnóstico por imagen , Colonoscopía , Neoplasias Colorrectales/diagnóstico , Detección Precoz del Cáncer , Adenoma/epidemiología , Anciano , Neoplasias Colorrectales/epidemiología , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Medición de Riesgo
17.
World J Gastrointest Endosc ; 13(10): 491-501, 2021 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-34733409

RESUMEN

BACKGROUND: In recent years, with the growing availability of image-enhanced gastrointestinal endoscopy, gastroenterologists have contributed to the early detection of pharyngeal squamous cell carcinomas (SCC). AIM: To clarify the clinical characteristics of pharyngeal SCCs detected by gastrointestinal endoscopy. METHODS: This is a retrospective cohort study conducted in a single-center, a university hospital in Japan. We retrospectively assessed the clinical records of 522 consecutive patients with oropharyngeal or hypopharyngeal SCC who were examined in our hospital between 2011 and 2018. The lesions were classified into two groups: Group GE (detected by gastrointestinal endoscopy) and Group non-GE (detected by means other than gastrointestinal endoscopy). The clinical characteristics were compared between the two groups. Continuous data were compared using the Mann-Whitney U test. Pearson's χ 2 test or Fisher's exact test was used to analyze the categorical data and compare proportions. The Kaplan-Meier method was used to estimate the cumulative patient survival rates. RESULTS: In our study group, the median age was 65 years and 474 patients (90.8%) were male. One hundred and ninety-six cases (37.5%) involved the oropharynx and 326 cases (62.5%) involved the hypopharynx. Three hundred and ninety-five cases (75.7%) had some symptoms at the time of diagnosis. One hundred and forty-five (27.8%) cases had concurrent ESCC or a history of ESCC. One hundred and sixty-four (31.4%) cases were detected by gastrointestinal endoscopy and classified as Group GE. The proportions of asymptomatic cases, cTis-1 cases and cases with no lymph node metastasis were significantly higher in Group GE than Group non-GE (61.6% vs 7.3%, P < 0.001, 32.9% vs 12.0%, P < 0.001 and 69.5% vs 19.0%, P < 0.001). Endoscopic laryngo-pharyngeal surgery or endoscopic submucosal dissection were performed in only 0.6% of the lesions in Group non-GE but in 21.3% of the lesions in Group GE (P < 0.001). Overall survival was significantly longer in Group GE than in Group non-GE (P = 0.018). The 2-year and 4-year survival rates were 82.5% and 70.7% in Group GE, and 71.5% and 59.0% in Group non-GE, respectively. CONCLUSION: Gastrointestinal endoscopy plays an important role in the early detection and improving the prognosis of pharyngeal SCCs.

18.
Intern Med ; 59(20): 2499-2504, 2020 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-32581160

RESUMEN

Immune checkpoint inhibitors can affect any organ, including the salivary glands. A case of Sjögren's syndrome (SjS) induced by nivolumab for the treatment of gastric cancer is herein presented. Nivolumab treatment caused marked tumor shrinkage, but xerostomia developed after two cycles. It took 3 months after symptom onset to confirm the diagnosis of SjS. Prednisolone and pilocarpine hydrochloride did not relieve the symptoms. SjS is a relatively rare immune-related adverse event that might sometimes be overlooked. Since SjS can severely impair a patient's quality of life, oncologists should not miss any signs of salivary gland hypofunction and cooperate with specialists for SjS.


Asunto(s)
Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Nivolumab/efectos adversos , Nivolumab/uso terapéutico , Síndrome de Sjögren/inducido químicamente , Síndrome de Sjögren/tratamiento farmacológico , Neoplasias Gástricas/tratamiento farmacológico , Femenino , Humanos , Pilocarpina/uso terapéutico , Prednisolona/uso terapéutico , Glándulas Salivales/fisiopatología , Síndrome de Sjögren/inmunología , Neoplasias Gástricas/complicaciones , Neoplasias Gástricas/inmunología , Xerostomía/inducido químicamente
19.
Case Rep Gastroenterol ; 14(1): 103-109, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32231510

RESUMEN

Although most immune-related adverse events (irAEs) secondary to immune checkpoint inhibitors can be managed with immunosuppressive therapies; they can induce reactivation of infectious diseases, including cytomegalovirus (CMV). Here, we show a case of CMV enterocolitis during steroid therapy for an irAE. A 77-year-old man with unresectable malignant melanoma was treated with ipilimumab. He suffered from immune-related colitis (irColitis) and was treated with methylprednisolone. Although corticosteroids initially improved his symptoms, CMV reactivation occurred and colitis was exacerbated. Antiviral therapy improved his symptoms without augmenting the immunosuppressive therapy. CMV colitis should be considered when a patient with irColitis shows resistance to immunosuppressive therapy.

20.
Radiol Case Rep ; 13(3): 709-712, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30050596

RESUMEN

We describe a case of small bowel Crohn's disease in which dual-energy computed tomography enterography using dual-layer spectral detector scanner contributed to quantitative assessment, and provided a higher degree of confidence pertaining to the diagnosis. Dual-layer spectral detector computed tomography enables retrospective analysis including virtual monochromatic imaging, iodine mapping, and determining the effective atomic number Z with routine scan protocols. These advanced parametric dual-energy imaging holds promising potential as an imaging biomarker for diagnosis, risk-stratification, monitoring of disease progression and therapy, and outcome prediction.

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