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2.
Kurume Med J ; 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38233185

RESUMO

Adenoid cystic carcinoma (ACC) is a major histological type of salivary gland cancer but an uncommon form of vulvar cancer. Salivary gland ACC occasionally dedifferentiates into high-grade carcinoma, resulting in poor prognoses. The dedifferentiated component is usually a poorly differentiated cribriform or solid carcinoma, whereas squamous cell carcinoma (SCC) is exceptional. Herein, we report the case of a 78-year-old woman with vulvar ACC, including an SCC component. She presented with a vulvar nodule that had been present for 30 years and increased in size over the past few years. Magnetic resonance imaging showed a ball-like mass with high intensity on T1-weighted images and high intensity with non-uniformity on T2-weighted images. Considering the systemic and social conditions, the tumor was maximally resected without lymphadenectomy. Histologically, the tumor was composed of a marginal ACC component with a central SCC component. Stage IB vulvar cancer, which was assumed to originate from the Bartholin's gland, was diagnosed. She has survived over 2 years without additional treatments after the surgery. In this case, we assumed that slowly progressive indolent ACC could be dedifferentiated to high- grade SCC. According to our review of available literature, dedifferentiation of vulvar ACC with a high-grade SCC component has not been specifically documented. Although the nature of dedifferentiated vulvar cancer is unclear, it should be noted that high-grade dedifferentiation can occur in long-lasting vulvar masses.

3.
J Cardiol Cases ; 29(1): 50-54, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38188325

RESUMO

Sinus of Valsalva aneurysm (SVA) is a rare cardiac anomaly that commonly originates from the right or noncoronary sinuses and rarely from the left sinus. SVA is usually diagnosed in the setting of clinical sequelae of a rupture. We herein report a case of an unruptured left SVA presenting as acute myocardial infarction. A 54-year-old woman with a history of radical operation for patent ductus arteriosus in childhood was transferred to our hospital. An electrocardiogram indicated extensive myocardial ischemia with ST elevation. Urgent coronary angiography was performed but was unable to identify the left coronary artery. Subsequent aortography and computed tomography revealed a large SVA originating from the left sinus and compressing the left coronary artery. The patient died after approximately one month of intensive care, including mechanical circulatory support and coronary artery bypass grafting. Autopsy confirmed that the left main coronary trunk was stretched and compressed by the SVA and revealed unexpected atherosclerosis in the left anterior descending artery. Although a left SVA is an extremely rare anomaly, it occasionally provokes fatal myocardial infarction. Since an SVA might hinder performing percutaneous coronary intervention, cardiac surgery should be considered when myocardial ischemia is recognized. Learning objective: We herein report a case of an unruptured left sinus of Valsalva aneurysm (SVA) with acute myocardial infarction. Urgent percutaneous coronary intervention (PCI) was unsuccessful, as the left coronary artery was compressed by the SVA. The patient died after intensive care, including coronary artery bypass grafting (CABG). SVA, especially from the left sinus, is extremely rare but occasionally provokes myocardial infarction by compressing the coronary arteries. Because SVA might hinder PCI, CABG should be considered when myocardial ischemia is recognized.

4.
Trop Med Health ; 52(1): 2, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38163868

RESUMO

BACKGROUND: Artificial intelligence-based computer-aided detection (AI-CAD) for tuberculosis (TB) has become commercially available and several studies have been conducted to evaluate the performance of AI-CAD for pulmonary tuberculosis (TB) in clinical settings. However, little is known about its applicability to community-based active case-finding (ACF) for TB. METHODS: We analysed an anonymized data set obtained from a community-based ACF in Cambodia, targeting persons aged 55 years or over, persons with any TB symptoms, such as chronic cough, and persons at risk of TB, including household contacts. All of the participants in the ACF were screened by chest radiography (CXR) by Cambodian doctors, followed by Xpert test when they were eligible for sputum examination. Interpretation by an experienced chest physician and abnormality scoring by a newly developed AI-CAD were retrospectively conducted for the CXR images. With a reference of Xpert-positive TB or human interpretations, receiver operating characteristic (ROC) curves were drawn to evaluate the AI-CAD performance by area under the ROC curve (AUROC). In addition, its applicability to community-based ACFs in Cambodia was examined. RESULTS: TB scores of the AI-CAD were significantly associated with the CXR classifications as indicated by the severity of TB disease, and its AUROC as the bacteriological reference was 0.86 (95% confidence interval 0.83-0.89). Using a threshold for triage purposes, the human reading and bacteriological examination needed fell to 21% and 15%, respectively, detecting 95% of Xpert-positive TB in ACF. For screening purposes, we could detect 98% of Xpert-positive TB cases. CONCLUSIONS: AI-CAD is applicable to community-based ACF in high TB burden settings, where experienced human readers for CXR images are scarce. The use of AI-CAD in developing countries has the potential to expand CXR screening in community-based ACFs, with a substantial decrease in the workload on human readers and laboratory labour. Further studies are needed to generalize the results to other countries by increasing the sample size and comparing the AI-CAD performance with that of more human readers.

5.
Medicine (Baltimore) ; 102(45): e35343, 2023 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-37960817

RESUMO

BACKGROUND: Lactobacillales including L mesenteroides have beneficial effects on human health, including improvement of psychological status and alleviation of allergic rhinitis. In mice, L mesenteroides subsp. strain NTM048 (NTM048) increased intestinal s-IgA. In humans, however, the effects of NTM048 on s-IgA secretion have been unclear. STUDY: This 16-week trial was performed using a double-blind, placebo-controlled, parallel group design. We aimed to establish whether Leuconostoc mesenteroides subsp. strain NTM048 increases the secretion of s-IgA in saliva. Forty healthy adults and forty patients with Japanese cedar pollinosis were recruited. Participants took either 2 test capsules including NTM048 (1010 CFU/day), or 2 placebo capsules per day, for 16 weeks. They were asked to collect their saliva and answered POMS2, a questionnaire about psychological status. The patients also answered questions about nasal symptoms. Blood samples were collected from the patients with Japanese Cedar pollinosis. Stool samples were collected at the start and on the last day of the trial. RESULTS: All subjects completed the trial. It was conducted during the season when Japanese cedar pollen is most scattered. Serum concentration of Japanese cedar pollen-specific IgE was > 2.0 UA/mL in patients with Japanese cedar pollinosis. The amount of s-IgA in saliva was not increased by NTM048 in overall subjects, and Japanese cedar pollen-specific IgE was not changed by NTM048 in patients with Japanese cedar pollinosis. The symptom of nasal blockage was improved by NTM048 12 weeks after the start of trial. post hoc analysis indicated a positive correlation between improving psychological status and the increase in occupation ratio of lactobacillus including NTM048. CONCLUSION: The amount of s-IgA in saliva was not increased by NTM048, but nasal blockage was improved by it. Psychological status might be improved if dosage of NTM048 is raised to the degree that NTM048 might be increased in the intestinal tract.


Assuntos
Leuconostoc mesenteroides , Obstrução Nasal , Rinite Alérgica Sazonal , Adulto , Humanos , Animais , Camundongos , Rinite Alérgica Sazonal/tratamento farmacológico , Japão , Imunoglobulina E , Imunoglobulina A/uso terapêutico
6.
Gan To Kagaku Ryoho ; 50(9): 1001-1004, 2023 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-37800297

RESUMO

The patient was an elderly man in his early 80s who was admitted to our hospital due to anemia and tarry stools. An upper gastrointestinal endoscopy revealed a type 2 tumor in the second portion of the duodenum. An endoscopic biopsy revealed poorly differentiated adenocarcinoma. We performed a pancreaticoduodenectomy because neither lymphadenopathy nor distant metastases were found. Macroscopic findings revealed that the lesion was mainly in the second portion of the duodenum, and there was no evidence of invasion of the main pancreatic duct, the bile duct, or the ampulla of Vater. Histologically, the tumor was composed of atypical cells with polymorphic or spindle-shaped nuclei proliferating in a scattered fashion, and immunohistological examinations showed weakly positive results for cytokeratin(CK)AE1/AE3 and CK20 and positive results for vimentin but negative results for CK7. The tumor was diagnosed as undifferentiated carcinoma of the duodenum(pT4N0M0, pStage ⅡB). The patient recovered enough to be discharged and was followed up without postoperative adjuvant chemotherapy. He maintained recurrence-free survival for 27 months, after which lymph node and lung metastases reoccurred. This is a rare case of undifferentiated carcinoma of the duodenum treated by curative resection with a relatively favorable prognosis.


Assuntos
Adenocarcinoma , Ampola Hepatopancreática , Carcinoma , Neoplasias do Ducto Colédoco , Humanos , Masculino , Adenocarcinoma/cirurgia , Ampola Hepatopancreática/cirurgia , Carcinoma/cirurgia , Neoplasias do Ducto Colédoco/patologia , Duodeno/patologia , Pancreatectomia , Pancreaticoduodenectomia , Idoso de 80 Anos ou mais
7.
Lancet Reg Health West Pac ; 36: 100770, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37547037

RESUMO

The Western Pacific has one of the fastest-growing older adult populations globally, and tuberculosis (TB) remains one of the foremost infectious causes of disease and death in the region. Older adults are at higher risk of TB due to immunosenescence, comorbidities, and increased institutionalisation. Atypical symptoms and reduced access to health services may delay care-seeking and TB diagnosis, while co-morbidity and increased risk of adverse drug reactions complicate TB treatment. Post-TB sequelae and socioeconomic challenges may decrease the quality of life after TB treatment completion. Despite their high disease burden and special challenges, there is a lack of regionally coordinated policies and guidelines to manage TB among older adults. Routine TB screening at aged-care facilities, age-friendly infrastructure and services, awareness of atypical TB features, integration of TB and non-communicable diseases services, and person-centred approaches to treatment support could improve TB management among older adults. Addressing these challenges and adopting the best practices identified should inform policy formulation and implementation. Funding: This project was funded by 1) the World Health Organization Regional Office for the Western Pacific, with financial contributions from the Government of the Republic of Korea through the Korean Disease Control and Prevention Agency and the Government of Japan through the Ministry of Health, Labour and Welfare, and 2) NUS Start-up Grant. The funders had no role in the paper design, collection, analysis, and interpretation of data and in writing of the paper.

9.
Cureus ; 15(5): e39138, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37332423

RESUMO

Few cases of acute respiratory distress syndrome (ARDS) in severe fever with thrombocytopenia syndrome (SFTS) have been treated with venovenous extracorporeal membrane oxygenation (VV-ECMO), and its role remains unclear. A 73-year-old Japanese woman presented with multiple organ failure (MOF) due to SFTS, including liver, neural, hematologic, renal, and ARDS. VV-ECMO for refractory hypoxemia under lung-protective ventilation with prone positioning led to gradual respiratory improvement, and she was successfully weaned on the 19th day of hospitalization. However, she died from persistent MOF on the 60th day of hospitalization. VV-ECMO contributed to recovery from ARDS but not from the ultimate cause of death, i.e., MOF. SFTS could have variable MOFs with different disease trajectories, which influence the decision for VV-ECMO.

10.
Eur J Trauma Emerg Surg ; 49(5): 2215-2224, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37300696

RESUMO

PURPOSE: The rate of surgical site infection (SSI) after surgery for secondary peritonitis is very high. This study investigated the relationship between intraoperative procedures of emergency surgery for nonappendiceal perforation peritonitis and deep incisional or organ-space SSI. METHODS: This prospective, two-center observational study included patients aged ≥ 20 years who underwent emergency surgery for perforation peritonitis between April 2017 and March 2020. We compared patients with deep incisional or organ-space SSI (Group S) to patients without SSIs or with superficial incisional SSIs (Group C). Thereafter, we evaluated the association between intraoperative technical variables and deep incisional or organ-space SSI using a multivariate logistic regression model. All multivariate analyses were adjusted for potentially relevant risk factors (e.g., age, body mass index, diabetes, smoking habit, and National Nosocomial Infection Surveillance risk index). RESULTS: Of the 75 participants, 14 were in Group S and 61 were in Group C. The use of a wound protector device was significantly associated with decreased odds of deep incisional or organ-space SSI (adjusted odds ratios [AOR], 0.017; 95% confidence intervals [CI] 0.0014-0.19, p = 0.0011). A 1000 ml increase in intra-abdominal lavage with normal saline was significantly associated with increased odds of deep incisional or organ-space SSI (AOR: 1.28, 95% CI 1.02-1.61, p = 0.033). CONCLUSION: Wound protector devices should be used in emergency surgery for nonappendiceal perforation peritonitis. Excessive intra-abdominal lavage with normal saline for peritonitis may have unsatisfactory benefits and increases the incidence of deep incisional or organ-space SSI.


Assuntos
Peritonite , Infecção da Ferida Cirúrgica , Humanos , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/prevenção & controle , Infecção da Ferida Cirúrgica/etiologia , Estudos Prospectivos , Solução Salina , Fatores de Risco , Incidência , Peritonite/prevenção & controle , Peritonite/cirurgia , Estudos Retrospectivos
11.
J Intensive Care ; 11(1): 20, 2023 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-37198714

RESUMO

BACKGROUND: Postoperative delirium in intensive care is common and associated with mortality, cognitive impairment, prolonged hospital stays and high costs. We evaluate whether a nurse-led orientation program could reduce the incidence of delirium in the intensive care unit after cardiovascular surgery. METHODS: In this retrospective cohort study, we enrolled patients admitted to the intensive care unit for planned cardiovascular surgery between January 2020 and December 2021. A nurse-led orientation program based on a preoperative visit was routinely introduced from January 2021. We assessed the association between these visits and postoperative delirium in the intensive care unit. We also assessed predictors of postoperative delirium with baseline and intraoperative characteristics. RESULTS: Among 253 patients with planned cardiovascular surgery, 128 (50.6%) received preoperative visits. Valve surgery comprised 44.7%, coronary surgery 31.6%, and aortic surgery 20.9%. Cardiopulmonary bypass use and transcatheter surgery were 60.5% and 12.3%, respectively. Incidence of delirium was lower in patients that received preoperative visits, and median hospital stay was shorter than in those without visits (18 patients [14.1%] vs 34 patients [27.2%], P < 0.01; 14 days vs 17 days, P < 0.01). After adjusting predefined confounders, preoperative visits were independently associated with decreased incidence of delirium (adjusted odds ratio [aOR] 0.45; 95% confidence interval [95% CI] 0.22-0.84). Other predictors of delirium were higher European System for Cardiac Operative Risk Evaluation II score and lower minimum intraoperative cerebral oxygen saturation. CONCLUSIONS: A preoperative nurse-led orientation program was associated with reduction of postoperative delirium and could be effective against postoperative delirium after cardiovascular surgery. Trial registration UMIN Clinical Trial Registry no. UMIN000048142. Registered 22, July, 2022, retrospectively registered, https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000054862 .

12.
Ann Med Surg (Lond) ; 85(4): 645-649, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37113907

RESUMO

Colorectal perforation with systemic peritonitis requires prompt surgical attention, and damage control surgery (DCS) is performed in patients with severe injuries. This study aimed to retrospectively investigate the efficacy of DCS in patients with colonic perforation. Materials and Methods: From January 2013 to December 2019, 131 patients with colorectal perforation underwent emergency surgery at our hospital. Among these, 95 patients required postoperative intensive care unit management and were included in this study; of these patients, 29 (31%) underwent DCS, and 66 (69%) underwent primary abdominal closure (PC). Results: Patients who underwent DCS had significantly higher Acute Physiology and Chronic Health Evaluation II (23.9 [19.5-29.5] vs. 17.6 [13.7-22]; P<0.0001) and Sequential Organ Failure Assessment (SOFA) (9 [7-11] vs. 6 [3-8]; P<0.0001) scores than did those who underwent PC. The initial operation time was significantly shorter for DCS than for PC (99 [68-112] vs. 146 [118-171]; P<0.0001). The 30-day mortality and colostomy rates were not significantly different between the two groups. Conclusions: The results suggest that DCS is useful in the management of acute generalized peritonitis caused by colorectal perforation.

13.
J Cardiol Cases ; 27(4): 137-140, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37012923

RESUMO

Adult T-cell leukemia/lymphoma (ATLL) is a mature peripheral T-cell neoplasm caused by human T-cell leukemia virus type I (HTLV-1) infection. Besides the oncogenic property, HTLV-1 causes HTLV-1-associated myelopathy/tropical spastic paraparesis and certain inflammatory diseases via a complex host immune response to latent virus infection. Cardiac involvement of ATLL is rare, with the majority of cases being disclosed in postmortem autopsy in patients with advanced subtypes. We herein report the case of a 64-year-old female patient with indolent chronic ATLL with severe mitral regurgitation. Although the condition of ATLL was stable, dyspnea on exertion gradually progressed over the course of three years and echocardiography revealed marked thickening of the mitral valve. Finally, the patient experienced hemodynamic collapse with atrial fibrillation and underwent surgical valve replacement. The removed mitral valve was grossly edematous and swollen. A histological examination revealed a granulomatous reaction mimicking the active phase of rheumatic valvulitis, with the infiltration of ATLL cells that were immunohistochemically positive for CD3, CD4, FoxP3, HLA-DRα, and CCR4. The postoperative course was uneventful, with the exception that Sjögren's syndrome was noted. The history of rheumatic fever was unclear, and such unique valvular pathology was presumably related to autoimmune mechanisms associated with HTLV-1 infection. Learning objective: We report a case of chronic adult T-cell leukemia/lymphoma (ATLL) with isolated valvular infiltration with a unique histology of granulomatous reaction. Human T-cell leukemia virus type I infection may accelerate autoimmune reactions and cardiac inflammation, irrespective of indolent clinical subtype. Among ATLL cases, possible progression of valvular insufficiency and heart failure in patients with cardiac symptoms should be carefully evaluated.

14.
BMC Musculoskelet Disord ; 24(1): 314, 2023 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-37087444

RESUMO

BACKGROUND: This study aimed to determine the feasibility of ultrasonography in the assessment of cervical vertebral artery (VA) injury as an alternative to computed tomography angiography (CTA) in the emergency room. METHODS: We analyzed 50 VAs from 25 consecutive patients with cervical spine injury that had been admitted to our emergency room. Ultrasonography and CTA were performed to assess the VA in patients with cervical spine injury. We examined the sensitivity and specificity of ultrasonography compared with CTA. RESULTS: Among these VAs, six were occluded on CTA. The agreement between ultrasonography and CTA was 98% (49/50) with 0.92 Cohen's Kappa index. The sensitivity, specificity, and positive and negative predictive values of ultrasonography were 100%, 97.7%, 85.7%, and 100%, respectively. In one case with hypoplastic VA, the detection of flow in the VA by ultrasonography differed from detection by CTA. Meanwhile, there were two cases in which VAs entered at C5 transverse foramen rather than at C6 level. However, ultrasonography could detect the blood flow in these VAs. CONCLUSIONS: Ultrasonography had a sensitivity of 100% compared with CTA in assessment of the VA. Ultrasonography can be used as an initial screening test for VA injury in the emergency room.


Assuntos
Lesões do Pescoço , Traumatismos da Coluna Vertebral , Humanos , Artéria Vertebral/diagnóstico por imagem , Artéria Vertebral/lesões , Angiografia/métodos , Ultrassonografia , Vértebras Cervicais/lesões , Serviço Hospitalar de Emergência
15.
Surg Case Rep ; 9(1): 46, 2023 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-36961559

RESUMO

BACKGROUND: Patients on long-term dialysis are prone to hemorrhagic complications, particularly uremic bleeding, but gallbladder hemorrhage is rare, even in patients on dialysis. There have been occasional reports of a Dieulafoy lesion being a cause of gastrointestinal hemorrhage, but its occurrence within the gallbladder is quite rare. This report describes a case of gallbladder hemorrhage from a Dieulafoy lesion in a patient on hemodialysis that was diagnosed early and successfully treated by laparoscopic cholecystectomy. CASE PRESENTATION: The patient was a 68-year-old woman on long-term hemodialysis with end-stage renal failure who presented with epigastralgia and back pain. There was no history of trauma or oral administration of antiplatelet or anticoagulant agents. There were no signs of an inflammatory reaction or hyperbilirubinemia. Contrast-enhanced computed tomography revealed a slightly hyperdense area in the distended gallbladder and extravasation within the gallbladder lumen but no gallstones. A severe atherosclerotic lesion was also found. She was diagnosed to have gallbladder hemorrhage and emergency laparoscopic cholecystectomy was performed. Although the postoperative course was complicated by drug fever, she was discharged on postoperative day 10 in a satisfactory condition. Histology revealed hemorrhagic ulceration with an exposed blood vessel accompanied by abnormal arteries in the submucosa. Arteriosclerosis with eccentric intimal hyperplasia in a small-sized artery was also seen. The diagnosis was gallbladder hemorrhage from a Dieulafoy lesion. CONCLUSIONS: A Dieulafoy lesion should be kept in mind as a cause of gallbladder hemorrhage in a patient with severe arteriosclerosis and a bleeding diathesis, particularly if on dialysis, and treated as early as possible.

16.
BMC Public Health ; 23(1): 370, 2023 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-36810018

RESUMO

BACKGROUND: The Western Pacific Region has one of the fastest-growing populations of older adults (≥ 65 years) globally, among whom tuberculosis (TB) poses a particular concern. This study reports country case studies from China, Japan, the Republic of Korea, and Singapore reflecting on their experiences in managing TB among older adults. FINDINGS: Across all four countries, TB case notification and incidence rates were highest among older adults, but clinical and public health guidance focused on this population was limited. Individual country reports illustrated a range of practices and challenges. Passive case finding remains the norm, with limited active case finding (ACF) programs implemented in China, Japan, and the Republic of Korea. Different approaches have been trialled to assist older adults in securing an early diagnosis, as well as adhering to their TB treatment. All countries emphasised the need for person-centred approaches that include the creative application of new technology and tailored incentive programs, as well as reconceptualisation of how we provide treatment support. The use of traditional medicines was found to be culturally entrenched among older adults, with a need for careful consideration of their complementary use. TB infection testing and the provision of TB preventive treatment (TPT) were underutilised with highly variable practice. CONCLUSION: Older adults require specific consideration in TB response policies, given the burgeoning aging population and their high TB risk. Policymakers, TB programs and funders must invest in and develop locally contextualised practice guidelines to inform evidence-based TB prevention and care practices for older adults.


Assuntos
Tuberculose Latente , Tuberculose , Humanos , Idoso , Tuberculose/epidemiologia , Incidência , Singapura , Envelhecimento
17.
Acute Med Surg ; 10(1): e823, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36844679

RESUMO

Background: Angioembolization for traumatic pancreaticoduodenal artery injury with unstable circulation, which characteristically requires a prolonged procedure time, does not yet have a standardized strategy for damage control interventional radiology. Case Presentation: We encountered two cases of rare traumatic pancreaticoduodenal artery injury wherein the patients were saved by a multidisciplinary team with a shared goal of clinical success, rather than the procedural success of angioembolization. Both patients treated with angioembolization had residual pseudoaneurysm or faint extravasation in the pancreaticoduodenal artery arcade. We prioritized critical care with preemptive plasma transfusion and aggressive blood pressure control, and planned repeat angiography. The patients showed no clinical signs of rebleeding or pseudoaneurysm based on computed tomography during follow-up. Conclusion: Our findings suggest that the permissive untreated pseudoaneurysm concept can be useful in developing damage control interventional radiology strategies for trauma cases with challenging time limitations, such as traumatic pancreaticoduodenal artery injury with circulatory collapse.

18.
Cell Mol Gastroenterol Hepatol ; 15(1): 99-119, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36210625

RESUMO

BACKGROUND & AIMS: Signal transducer and activator of transcription 3 (STAT3) is known as a pro-oncogenic transcription factor. Regarding liver carcinogenesis, however, it remains controversial whether activated STAT3 is pro- or anti-tumorigenic. This study aimed to clarify the significance and mechanism of STAT3 activation in hepatocellular carcinoma (HCC). METHODS: Hepatocyte-specific Kras-mutant mice (Alb-Cre KrasLSL-G12D/+; KrasG12D mice) were used as a liver cancer model. Cell lines of hepatoma and stromal cells including stellate cells, macrophages, T cells, and endothelial cells were used for culture. Surgically resected 12 HCCs were used for human analysis. RESULTS: Tumors in KrasG12D mice showed up-regulation of phosphorylated STAT3 (p-STAT3), together with interleukin (IL)-6 family cytokines, STAT3 target genes, and connective tissue growth factor (CTGF). Hepatocyte-specific STAT3 knockout (Alb-Cre KrasLSL-G12D/+ STAT3fl/fl) downregulated p-STAT3 and CTGF and suppressed tumor progression. In coculture with stromal cells, proliferation, and expression of p-STAT3 and CTGF, were enhanced in hepatoma cells via gp130/STAT3 signaling. Meanwhile, hepatoma cells produced CTGF to stimulate integrin/nuclear factor kappa B signaling and up-regulate IL-6 family cytokines from stromal cells, which could in turn activate gp130/STAT3 signaling in hepatoma cells. In KrasG12D mice, hepatocyte-specific CTGF knockout (Alb-Cre KrasLSL-G12D/+ CTGFfl/fl) downregulated p-STAT3, CTGF, and IL-6 family cytokines, and suppressed tumor progression. In human HCC, single cell RNA sequence showed CTGF and IL-6 family cytokine expression in tumor cells and stromal cells, respectively. CTGF expression was positively correlated with that of IL-6 family cytokines and STAT3 target genes in The Cancer Genome Atlas. CONCLUSIONS: STAT3 is activated by CTGF-mediated tumor-stroma crosstalk to promote HCC progression. STAT3-CTGF positive feedback loop could be a therapeutic target.


Assuntos
Carcinoma Hepatocelular , Fator de Crescimento do Tecido Conjuntivo , Neoplasias Hepáticas , Fator de Transcrição STAT3 , Animais , Humanos , Camundongos , Carcinogênese , Carcinoma Hepatocelular/genética , Fator de Crescimento do Tecido Conjuntivo/genética , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Receptor gp130 de Citocina/metabolismo , Células Endoteliais , Interleucina-6/metabolismo , Neoplasias Hepáticas/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Fator de Transcrição STAT3/metabolismo
19.
Spine Surg Relat Res ; 6(5): 464-471, 2022 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-36348683

RESUMO

Introduction: Massive hemothorax due to thoracic vertebral fractures (MHTVF) is a potentially lethal condition; however, its epidemiological and clinical data have been rarely described. Thus, in this study, we aimed to evaluate the incidence, predictive factors, and clinical features of MHTVF. Methods: This retrospective cohort study enrolled 202 consecutive patients (136 male and 66 female patients) with thoracic vertebral fractures treated at our institute between January 2009 and December 2019. Their mean age was 60.7 (range, 17-90) years. Unstable fractures accounted for 57.4% (n=116) of the total fractures. The patients were then divided into MHTVF and non-MHTVF groups. We assessed the following MHTVF-associated factors: sex, age, history of medical conditions, anticoagulation/antiplatelet drug use, injury severity score, anatomical distribution of levels of the vertebral fractures, fracture type, and presence or absence of diffuse idiopathic skeletal hyperostosis (DISH) fracture. Results: In total, eight patients (six men and two women) with a mean age of 68.9 years (range, 22-85 years) were determined to exhibit MHTVF. The incidence of MHTVF in patients with unstable thoracic spinal fractures was 6.9%, whereas none of those with stable spinal fractures exhibited MHTVF. Factors like type B (p=0.049) and DISH (p=0.017) fractures were noted to be significantly associated with the MHTVF. Three patients experienced shock upon arrival, whereas two exhibited delayed shock. Chest tube insertion and/or emergency thoracotomy was performed. The survival rate was 100.0%. Conclusions: MHTVF is not rare. Because type B and DISH fractures are identified as predictive factors of MHTVF, it must be carefully treated to avoid preventable death even after hospitalization in patients with these thoracic fractures.

20.
Cancer Sci ; 113(12): 4311-4326, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36074525

RESUMO

Cancer cachexia, a paraneoplastic syndrome characterized by ongoing skeletal muscle mass loss, is accompanied by adipose tissue loss and strongly affects chemotherapy endurance. Our aim was to detect a serum marker reflecting pancreatic cancer cachexia and predicting subsequent loss of muscle mass and adipose tissue, focusing on adipose tissue-secreted proteins. Murine-derived pancreatic cancer cells were orthotopically injected into the mouse pancreatic tail. After 3 weeks, RNA sequencing of perigonadal fat and orthotopic tumors was carried out. We analyzed stocked sera and clinical data of metastatic pancreatic cancer patients who received chemotherapy. Perigonadal fat weight/body weight decreased in mice with orthotopic tumors compared to those without tumors. By RNA sequencing and real-time PCR validation, pentraxin 3 (PTX3) was identified as a secreted protein-encoded gene whose expression was significantly higher in the perigonadal fat of mice with orthotopic tumors than in that of mice without orthotopic tumors and was least expressed in orthotopic tumors. Serum PTX3 levels correlated with PTX3 mRNA levels in perigonadal fat and were higher in mice with orthotopic tumors than in those without tumors. In 84 patients diagnosed with metastatic pancreatic cancer, patients with high serum PTX3 levels showed a greater visceral fat loss/month and skeletal muscle mass index (SMI) decrease/month than those with low serum PTX3 levels. High serum PTX3 was an independent risk factor for visceral fat loss, decreased SMI, and poor prognosis. High serum PTX3 in pancreatic cancer patients predicts visceral fat and muscle mass loss and major clinical outcomes of cancer cachexia.


Assuntos
Gordura Intra-Abdominal , Neoplasias Pancreáticas , Camundongos , Animais , Gordura Intra-Abdominal/metabolismo , Gordura Intra-Abdominal/patologia , Caquexia/etiologia , Neoplasias Pancreáticas/genética , Tecido Adiposo , Biomarcadores/metabolismo , Músculos/metabolismo , Músculo Esquelético/patologia , Neoplasias Pancreáticas
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