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This paper presents the first version of clinical practice guidelines for intrahepatic cholangiocarcinoma (ICC) established by the Liver Cancer Study Group of Japan. These guidelines consist of 1 treatment algorithm, 5 background statements, 16 clinical questions, and 1 clinical topic, including etiology, staging, pathology, diagnosis, and treatments. Globally, a high incidence of ICC has been reported in East and Southeast Asian countries, and the incidence has been gradually increasing in Japan and also in Western countries. Reported risk factors for ICC include cirrhosis, hepatitis B/C, alcohol consumption, diabetes, obesity, smoking, nonalcoholic steatohepatitis, and liver fluke infestation, as well as biliary diseases, such as primary sclerosing cholangitis, hepatolithiasis, congenital cholangiectasis, and Caroli disease. Chemical risk factors include thorium-232, 1,2-dichloropropane, and dichloromethane. CA19-9 and CEA are recommended as tumor markers for early detection and diagnostic of ICC. Abdominal ultrasonography, CT, and MRI are effective imaging modalities for diagnosing ICC. If bile duct invasion is suspected, imaging modalities for examining the bile ducts may be useful. In unresectable cases, tumor biopsy should be considered when deemed necessary for the differential diagnosis and drug therapy selection. The mainstay of treatment for patients with Child-Pugh class A or B liver function is surgical resection and drug therapy. If the patient has no regional lymph node metastasis (LNM) and has a single tumor, resection is the treatment of choice. If both regional LNM and multiple tumors are present, drug therapy is the first treatment of choice. If the patient has either regional LNM or multiple tumors, resection or drug therapy is selected, depending on the extent of metastasis or the number of tumors. If distant metastasis is present, drug therapy is the treatment of choice. Percutaneous ablation therapy may be considered for patients who are ineligible for surgical resection or drug therapy due to decreased hepatic functional reserve or comorbidities. For unresectable ICC without extrahepatic metastasis, stereotactic radiotherapy (tumor size ≤5 cm) or particle radiotherapy (no size restriction) may be considered. ICC is generally not indicated for liver transplantation, and palliative care is recommended for patients with Child-Pugh class C liver function. [ABSTRACT FROM AUTHOR]

Liver damage caused by hepatitis B virus (HBV) infections is diffuse. Live medical images and FibroScan images show that it is inhomogeneous. Modeling and interpreting such phenomena are both important for theoretical research and practical application. The cellular neural networks (CNNs) introduced by Chua and Yang can model widely observed patterns in both nonbiological and biological media. The sawtooth and rectangle (SR) CNN introduced by Chua and colleagues is able to generate SR-shaped patterns for any random-input grayscale patterns, which are also similar to some chronic HBV-infected patients' liver B-scan images. This paper will mathematically study the dynamic behaviors of the SR CNN, numerically simulate the output images of the SR CNN, and biologically interpret the relationships between the output images of the SR CNN and the patterns in HBV-infected patients' liver B-scan images. Our research results show that the SR CNN may be used as a candidate for modeling liver infections. [ABSTRACT FROM AUTHOR]

Introduction: Hepatocellular carcinoma (HCC) is the sixth most commonly diagnosed cancer and the third leading cause of cancer death worldwide. While there has been rapid evolution in the treatment paradigm of HCC across the past decade, the extent to which these newly approved therapies are utilized in clinical practice in the real world is, however, unknown. The INSIGHT study was an investigator-initiated, multi-site longitudinal cohort study conducted to reflect real-world epidemiology and clinical practice in Asia-Pacific in the immediate 7-year period after the conclusion of the BRIDGE study. Methods: Data were collected both retrospectively (planned 30% of the total cohort size) and prospectively (planned 70%) from January 2013 to December 2019 from eligible patients newly diagnosed with HCC from 33 participating sites across 9 Asia-Pacific countries. Results: A total of 2,533 newly diagnosed HCC patients (1,052 in retrospective cohort and 1,481 in prospective cohort) were enrolled. The most common risk factor was hepatitis B in all countries except Japan, Australia, and New Zealand, where the prevalence of hepatitis C and diabetes were more common. The top three comorbidities reported in the INSIGHT study include cirrhosis, hypertension, and diabetes. We observe high heterogeneity in the first-line treatment recorded across countries and across disease stages, which significantly affects survival outcomes. Stratification by factors such as etiologies, tumor characteristics, the presence of extrahepatic metastases or macrovascular invasion, and the use of subsequent lines of treatment were performed. Conclusion: The INSIGHT study describes a wide spectrum of clinical management practices in HCC, where patient demographics, differential costs, and patient access to therapies may lead to wide geographical variations through the patient's treatment cycle, from diagnosis to clinical outcome. The high heterogeneity in patient outcomes demonstrates the need for more robust and clinical management strategies to be designed and adopted to bring about better patient outcomes. [ABSTRACT FROM AUTHOR]

Tumor lysis syndrome (TLS) is an oncologic emergency characterized by the destruction of tumor cells leading to an influx of large amounts of uric acid, potassium, and phosphorus into systemic circulation. It most often occurs after the initiation of cytotoxic therapy in high-grade lymphomas and leukemias; however, rarely it may occur spontaneously. The authors report a case of spontaneous tumor lysis causing electrolyte abnormalities and acute kidney injury in a patient with subsequently diagnosed large chronic lymphocytic leukemia tumor burden. Spontaneous TLS can be the first presentation of underlying malignancy; therefore, physicians should be aware of the associated findings. [ABSTRACT FROM AUTHOR]

Keloidal atypical fibroxanthoma (KAF) has recently been categorized as a variant of atypical fibroxanthoma. This paper will emphasize the importance of including KAF in both clinical and histological differential diagnosis of benign and malignant lesions which exhibit keloidal collagen and will also review the current literature on epidemiology, pathogenesis, histology, immunochemistry and treatments. [ABSTRACT FROM AUTHOR]

A patient presented with complaints of a sudden decrease in vision, ocular redness, and pain in the right eye. The patient had a history of clear lens extraction with intraocular lens (IOL) implantation for myopia 2 years previously. He had been prescribed topical steroids for episodes of inflammation that occurred repeatedly every 1–2 months. With a presumptive diagnosis of chronic endophthalmitis, a 23-G transconjunctival sutureless pars plana vitrectomy (PPV) with delivery of intravitreal antibiotics was performed the next day. Culture sensitivity testing of the vitreous sample indicated Pseudomonas stutzeri that was sensitive to ceftazidime and gentamicin. Two weeks later, the patient presented with sudden loss of vision and all the signs of recurrent endophthalmitis. 23-G transconjunctival sutureless PPV was performed along with removal of the posterior chamber IOL through a corneal incision. Complete resolution was only achieved after removal of the IOL, resulting in excellent visual recovery. Due to its chronic and fulminating nature, P. stutzeri can induce endophthalmitis and should be considered in the differential diagnosis. Aseptic measures are the best prevention. [ABSTRACT FROM AUTHOR]

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a rare inflammatory disorder featured by pontocerebellar dysfunctions and, in some cases, later cognitive disturbances. Here, we describe an atypical presentation of CLIPPERS, characterized by clinical onset with neuropsychiatric and cognitive symptoms. A 45-year-old man was referred to our Memory Clinic due to difficulties at work for over a month, caused by confusion and asthenia. Furthermore, insomnia and mood changes appeared. These disturbances were unresponsive to antipsychotic and antidepressant drugs. At admission, the patient presented also with severe cognitive impairment, urinary incontinence, ataxic gait, and limitation of lateral conjugate gaze. During the hospitalization, the patient underwent cerebrospinal fluid analysis, serum systemic autoimmune disorders laboratory research, neoplastic markers analysis, and brain MRI scan. The radiological and laboratory findings were compatible with the diagnosis of CLIPPERS. The sudden clinical and radiological improvement of the patient's conditions, after only a week of steroid therapy, further confirmed our clinical suspicion. The present case enhances the necessity to consider CLIPPERS in the differential diagnosis of pre-senile cognitive impairment, even in the absence of early pontocerebellar neurological signs. Before the spreading of the neuroinflammatory and degenerative processes, CLIPPERS represents one among the few possible reversible causes of cognitive decline. [ABSTRACT FROM AUTHOR]

Background: Combined hepatocellular-cholangiocarcinoma (cHCC-iCCA) is a rare type of primary liver cancer displaying characteristics of both hepatocytic and cholangiocytic differentiation. Summary: Because of its aggressive nature, patients with cHCC-iCCA exhibit a poorer prognosis than those with HCC. Surgical resection and liver transplantation may be considered curative treatment approaches; however, only a minority of patients are eligible at the time of diagnosis, and postoperative recurrence rates are high. For cases that are not eligible for surgery, locoregional and systemic therapy are often administered based on treatment protocols applied for HCC or iCCA. Owing to the rarity of this cancer, there are still no established standard treatment protocols; therefore, the choice of therapy is often personalized and guided by the suspected predominant component. Further, the genomic and molecular heterogeneity of cHCC-iCCA can severely compromise the efficacy of the available therapies. Key Messages: In the present review, we summarize the latest advances in cHCC-iCCA and attempt to clarify its terminology and molecular biology. We provide an overview of the etiology of cHCC-iCCA and present new insights into the molecular pathology of this disease that could contribute to further studies aiming to improve the patient outcomes through new systemic therapies. [ABSTRACT FROM AUTHOR]

The Breast Committee of the Arbeitsgemeinschaft Gynäkologische Onkologie (German Gynecological Oncology Group, AGO) presents the 2023 update of the evidence-based recommendations for the diagnosis and treatment of patients with locally advanced and metastatic breast cancer (mBC). [ABSTRACT FROM AUTHOR]

Background: MicroRNAs play an important role in the proliferation and migration of retinal endothelial cells in patients with hypertension and hypertensive retinopathy (HR). This study aimed to investigate the clinical value of miR-637 in HR and its role in retinal endothelial cell proliferation and migration. Methods: A total of 126 subjects were recruited for the study, including 42 patients with hypertension (male/female 25/17), 42 healthy individuals (male/female 20/22), and 42 cases with HR (male/female 20/22). Except SBP and DBP, there was no significant difference in other indexes among the three groups. Quantitative real-time PCR was used to detect the expression of miR-637. The receiver operating curve (ROC) was used for diagnosis value analysis. Logistic regression analysis was used to evaluate the relationship between miR-637 and HR. CCK-8 and Transwell were used to detect the effect of miR-637 on the proliferation and migration of human umbilical vein endothelial cells. Results: Compared with hypertensive patients, HR patients had the lowest expression of miR-637. The area under the curve of miR-637 detected by the ROC curve method is 0.892, which has the ability to distinguish hypertension and HR patients. Logistic regression analysis showed that miR-637 was an independent influencing factor in HR. Cell experiment results showed that overexpression of miR-637 significantly inhibited cell proliferation and migration, while downregulation of miR-637 had the opposite effect. Luciferase analysis showed that STAT3 was the target gene of miR-637. Conclusion: Our data indicate that miR-637 is a potential noninvasive marker for patients with HR. The action of miR-637 on STAT3 may inhibit the proliferation and migration of retinal endothelial cells, providing a possible target for the treatment of HR. [ABSTRACT FROM AUTHOR]

The Breast Committee of the Arbeitsgemeinschaft Gynäkologische Onkologie (German Gynecological Oncology Group, AGO) presents the 2022 update of the evidence-based recommendations for the diagnosis and treatment of patients with locally advanced and metastatic breast cancer. [ABSTRACT FROM AUTHOR]

Diverting stoma (DS) is widely created in colorectal surgery. High-output stoma (HOS) is a major complication of DS, which can lead to dehydration and thrombosis. Additionally, antiphospholipid syndrome (APS) is a risk factor for thrombosis, and it rarely occurs in men. Herein, we describe a case of multiple thromboses caused by chronic dehydration after HOS. A 48-year-old man visited our hospital with fever and lower abdominal pain; he was diagnosed with sigmoid diverticulitis. He underwent laparoscopic high anterior resection for relapsing diverticulitis and diverting ileostomy during the same operation. On postoperative day 1, an output of 3,000 mL/day was observed from the ileostomy. The stoma output exceeded 2,000 mL/day, which was diagnosed as HOS, and chronic dehydration persisted despite supplementation and restriction of oral water intake. Three months postoperatively, a computed tomography scan before ileostomy closure showed multiple thrombi in the inferior vena cava, right common iliac vein, and pulmonary artery. After antithrombotic therapy, ileostomy closure was performed. As lupus anticoagulant was positive twice and APS was diagnosed, antithrombotic therapy was changed from warfarin to direct oral anticoagulants. Thrombosis did not recur 6 months postoperatively. This is the first report of a case wherein APS was present in the background of thrombosis caused by HOS or chronic dehydration. It is important to be cautious about APS when there is thrombosis after HOS to select appropriate therapeutic agents. [ABSTRACT FROM AUTHOR]

Ewing sarcoma and primitive neuroectodermal tumors (ES/PNETs) are rare tumors that belong to a family of round-cell neuroectodermally derived tumors, and their optimal treatment remains a great challenge. This study presented a case of ES/PNET, arising in the esophagus of a 21-year-old female patient presented with progressive dysphagia. Computed tomography and endoscopic ultrasonography showed a well-defined, submucosal solid mass in the superthoracic esophagus. The accurate diagnosis after surgery was obtained through immunohistochemistry and genetic studies, namely the CD99 immunopositivity as well as the EWSR1/FLI1 gene rearrangement associated with t(11;22)(q24;q12) in tumor cells. The patient underwent localized tumor resection followed by chemotherapy and chest radiotherapy. The patient is doing well with no evidence of tumor recurrence or metastasis 18 months after surgery. Although the esophagus is a rare site for ES/pPNET, we can speculate that the treatment protocol of ES/pPNET should include multi-agent chemotherapy, surgery, and local radiotherapy in order to improve the prognosis based on our report. [ABSTRACT FROM AUTHOR]

Introduction: Obesity is a major risk factor for metabolic disorders in children. Therefore, it is particularly important to study the abnormal regulation of circulating miR-24-3p in obese children and its predictive value for metabolic syndrome. Methods: Serum samples were obtained from children with obesity (n = 45), obese children with metabolic syndrome (n = 52), and healthy controls (n = 50). The expression levels of miR-24-3p were detected by reverse transcription quantitative PCR. The ROC curve was used to evaluate the diagnostic value of miR-24-3p. Pearson's correlation analysis was performed to evaluate the relationship between serum miR-24-3p and different clinical parameters. Logistic regression analysis was used to evaluate the relationship between miR-24-3p and obesity with metabolic syndrome in children. Results: The expression of miR-24-3p was the highest in obese children with metabolic syndrome. ROC results showed that miR-24-3p had the ability to distinguish healthy individuals from obese children (area under the curve [AUC] = 0.951) and can predict the occurrence of metabolic syndrome for obese children (AUC = 0.890). The expression level of miR-24-3p was positively correlated with body mass index (r = 0.817, p < 0.001), fasting blood glucose (r = 0.798, p < 0.001), triglycerides (r = 0.773, p < 0.001), systolic blood pressure (r = 0.746, p < 0.001), and diastolic blood pressure (r = 0.623, p < 0.001), respectively. Logistic regression analysis showed that miR-24-3p was an independent influence factor for the occurrence of metabolic syndrome in obese children. Discussion/Conclusion: MiR-24-3p is a potential noninvasive marker for children with obesity and has predictive value for the occurrence of metabolic syndrome. [ABSTRACT FROM AUTHOR]

TAFRO syndrome is defined by the presence of thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis/renal dysfunction (R), and organomegaly (O) and can be seen with idiopathic multicentric Castleman disease (iMCD) or as an isolated process without iMCD. Although the diagnosis of iMCD in patients with TAFRO can be challenging to make, iMCD should remain high on the differential diagnosis. Similar to iMCD, the pathophysiology of TAFRO is not well understood but is thought to be related to hypercytokinemia, with interleukin (IL)-6 playing a pivotal role. Anti-IL-6 monoclonal antibody therapy is an effective treatment modality for iMCD, but to date, there is no clear guidance on treatment of TAFRO in the absence of definitive diagnosis of iMCD, leading to suboptimal management and high morbidity. We report a case of TAFRO syndrome and demonstrate benefit with the empiric use of anti-IL-6 antibody therapy in the context of delayed diagnosis of iMCD. [ABSTRACT FROM AUTHOR]

Autoimmune encephalitis (AE) is a group of inflammatory brain diseases that are characterized by prominent neuropsychiatric symptoms. Early therapeutic intervention is important for AE. Therefore, without waiting for autoantibody test results, clinicians must consider the possibility of AE based solely on clinical symptoms and conventional test results. The case described herein is of antibody-negative encephalitis with abnormalities shown only by EEG, which contributed to the diagnosis and treatment. The patient, a 20-year-old woman, showed autonomic seizures in addition to movement disorders, psychiatric symptoms, and cognitive dysfunction, which worsened subacutely. Her seizures and movement disorders were not responsive to antiepileptic medications. Results obtained from MRI and cerebrospinal fluid (CSF) were normal; EEG findings showed repeated spikes in the right temporal area, with changes over time. Based on the clinical course and EEG, along with administered immunotherapy, which resolved seizures, movement disorders, and psychiatric symptoms, we suspected AE. For diagnosis of AE and for evaluating treatment responsiveness, EEG was useful. Results indicate that EEG can assist clinicians even with AE cases for which MRI and CSF findings are normal. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study was to retrospectively evaluate the prevalence of reported and unreported potentially important incidental findings (PIFs) in consecutive nonenhanced abdominal CTs performed specifically for renal colic in the urgent setting.Methods: One radiologist, blinded to the finalized report, retrospectively re-evaluated nonenhanced abdominal CTs performed from January to December 2017 on adult patients from the emergency department with the specific request of urgent evaluation for renal colic, searching for PIFs.Results: The CTs of 312 patients were included in the study. Thirty-eight findings were reported in 38 different CTs, whereas the re-evaluation added 47 unreported findings in 47 different CTs, adding to total of 85 findings (27%). The difference in the proportion of reported and unreported PIFs between the original report and re-evaluation was significant (p < 0.001). No significant difference was found between the age of patients with and without reported findings. The proportion of potentially important findings did not vary significantly among the 3 shifts in the original report and in re-evaluation. The most frequent findings, both reported and unreported, were pleural effusion, lymphadenopathies, and liver nodules.Conclusions: Potentially important additional findings are frequently present in urgent nonenhanced abdominal CTs performed for renal colic, and many are not described in the finalized reports. Radiologists should take care not to underreport PIFs even in the urgent setting because of the possible consequences on the patient's health and in order to avoid legal issues, while at the same time satisfying the need for timely and efficient reporting. [ABSTRACT FROM AUTHOR]

Lupus miliaris disseminatus faciei (LMDF) and granulomatous rosacea are 2 distinct inflammatory dermatoses with overlapping clinical features: reddish-yellow papular eruptions localized on the central face. Consequently, LMDF can easily be misdiagnosed as granulomatous rosacea or vice versa. Because delayed treatment in LMDF may increase chances of permanent scar formation, accurate diagnosis is important. We therefore analyzed published literature and case studies to organize the essential features differentiating LMDF from granulomatous rosacea. In addition, we report each case of LMDF and granulomatous rosacea for direct comparison. [ABSTRACT FROM AUTHOR]

We report a case of ulcerative lupus vulgaris (LV) in a unique site, which facilitated the detection of internal organ tuberculosis (TB). A 68-year-old Japanese man presented with a reddish ulcerated painless lesion on his right wrist that had initially appeared 4 weeks earlier as a nontender nodule. There was no recent history of fever, weight loss, or cough. The results of tissue culture, PCR, and contrast-enhanced chest computed tomography were consistent with the diagnosis of ulcerative LV with underlying pulmonary TB and tuberculous lymphadenitis. The patient was started on anti-TB therapy. After 1 month of therapy, epithelialization of the ulcer was noted. [ABSTRACT FROM AUTHOR]

Celiac disease is an immune-mediated disease, affecting multiple systems and organs including several dermatological conditions. Morphea, or localized scleroderma, is also an immune-mediated condition, in which an association with celiac disease has not thus far been recognized. We present an interesting case report of a 10-year-old child with a recent diagnosis of celiac disease presenting with morphea. Following treatment and adherence to a gluten-free diet, the morphea rapidly resolved. We suggest a possible relationship between the two entities and give a brief review of the relevant literature. We suggest that morphea might be one of the many dermatological manifestations of celiac disease, with possible implications for the need to screen patients with morphea for celiac disease. [ABSTRACT FROM AUTHOR]

The Clinical Practice Manual for Hepatocellular Carcinoma was published based on evidence confirmed by the Evidence-based Clinical Practice Guidelines for Hepatocellular Carcinoma along with consensus opinion among a Japan Society of Hepatology (JSH) expert panel on hepatocellular carcinoma (HCC). Since the JSH Clinical Practice Guidelines are based on original articles with extremely high levels of evidence, expert opinions on HCC management in clinical practice or consensus on newly developed treatments are not included. However, the practice manual incorporates the literature based on clinical data, expert opinion, and real-world clinical practice currently conducted in Japan to facilitate its use by clinicians. Alongside each revision of the JSH Guidelines, we issued an update to the manual, with the first edition of the manual published in 2007, the second edition in 2010, the third edition in 2015, and the fourth edition in 2020, which includes the 2017 edition of the JSH Guideline. This article is an excerpt from the fourth edition of the HCC Clinical Practice Manual focusing on pathology, diagnosis, and treatment of HCC. It is designed as a practical manual different from the latest version of the JSH Clinical Practice Guidelines. This practice manual was written by an expert panel from the JSH, with emphasis on the consensus statements and recommendations for the management of HCC proposed by the JSH expert panel. In this article, we included newly developed clinical practices that are relatively common among Japanese experts in this field, although all of their statements are not associated with a high level of evidence, but these practices are likely to be incorporated into guidelines in the future. To write this article, coauthors from different institutions drafted the content and then critically reviewed each other's work. The revised content was then critically reviewed by the Board of Directors and the Planning and Public Relations Committee of JSH before publication to confirm the consensus statements and recommendations. The consensus statements and recommendations presented in this report represent measures actually being conducted at the highest-level HCC treatment centers in Japan. We hope this article provides insight into the actual situation of HCC practice in Japan, thereby affecting the global practice pattern in the management of HCC. [ABSTRACT FROM AUTHOR]

Many reports have described a high incidence of acute kidney injury (AKI) among patients with COVID-19. Acute tubular necrosis has been reported to be the most common damage in these patients, probably due to hemodynamic instability. However, other complex processes may be involved, related to the cytokine storm and the activation of innate and adaptive immunity. Here, we describe a patient who developed an antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis with rapidly progressive glomerulonephritis and lung involvement and an antiphospholipid syndrome soon after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. After viral pneumonia was excluded by bronchoalveolar lavage, the patient has been treated with rituximab for amelioration of kidney function and resolution of thrombosis without any adverse event. We conclude that COVID-19 may trigger autoimmune diseases including ANCA-associated vasculitis. Thus, this diagnosis should be taken in consideration in COVID-19 patients, especially when they develop AKI with active urinary sediment. In addition, considering the relationship between these 2 diseases, SARS-CoV-2 infection should be excluded in all patients with a new diagnosis ANCA-associated vasculitis before starting immunosuppressive therapy. [ABSTRACT FROM AUTHOR]

Lymphatic-venous malformations (LVMs) are development defects that result in abnormal connections between the lymphatic and venous systems. The authors describe a 7-weeks-old female infant who presented with a right orbital LVM extending to the ipsilateral cheek and subconjunctiva of the right eye, intracranial developmental venous anomalies in the right cerebellum, and a significant right eye intraocular retinal vascular malformation. Since orbital LVM is usually diagnosed in infancy or childhood, pediatric ophthalmologists should actively look for intraocular vascular malformations as such findings can poorly affect a patient's vision. [ABSTRACT FROM AUTHOR]

Pregnancy with choriocarcinoma is a rare tumor. It is rare for neonates to survive the third trimester. This article reports the clinical data of a live fetal pregnancy with choriocarcinoma complicated by brain and lung metastases. The patient was admitted to the hospital for "menopause 28 weeks + 5 days, dizziness with nausea and vomiting 2 days." After 5 hours of admission, the patient had sudden convulsions, urinary incontinence, and coma. A head computed tomography (CT) examination in the emergency department revealed a cerebral hemorrhage in the right occipital lobe and broke into the ventricular system with brain herniation. She was immediately transferred to the intensive care unit for the emergency cesarean section and intracerebral hematoma removal. A postoperative CT scan revealed that the tumor in the upper lobe of the right lung was considered lung cancer, with multiple metastases in both lungs. Postoperative pathology was metastatic choriocarcinoma tissue seen in the blood clot. Based on the pathological diagnosis of choriocarcinoma, a chemotherapy regimen was developed with 2 courses of EP regimen and 8 courses of combined EMA-CO chemotherapy regimen. The patients were followed up for 2 years and ultimately resolved. [ABSTRACT FROM AUTHOR]

Eccrine porocarcinoma is a rare malignant cutaneous tumor with high rates of extracutaneous spread, and its diagnosis and management can be quite challenging. This is a case of an 82-year-old woman presenting with an asymptomatic and chronic pubic skin lesion for whom the work-up required many investigations and procedures to confirm the diagnosis of metastatic eccrine porocarcinoma. Indeed, the patient underwent a wide local excision of the skin lesion, imaging with an FDG-PET scan, a colonoscopy, and two inguinal node dissections. As illustrated in this case, surgery should always be considered to achieve disease remission. Other treatments such as chemotherapy and radiotherapy have also been reported in the literature without clear standard guidelines. [ABSTRACT FROM AUTHOR]

Generalized weakness in the pediatric and adolescent population is caused by many disorders that affect the neuromuscular axis. As next-generation sequencing (NGS) is becoming of high yield in replacing more invasive procedures, that is, muscle and nerve biopsy, more previously undiagnosed diseases of the muscles are now labeled with specific pathogenicity. A 16-year-old-girl diagnosed with nemaline myopathy but previously was misdiagnosed with congenital myasthenia and put-on unnecessary medications. Clinicians should be aware of congenital diseases that affect the muscles and know the importance of the NGS in reaching the correct diagnosis more so when there is a history of consanguinity. [ABSTRACT FROM AUTHOR]

Frontotemporal dementia (FTD) is a neuropsychiatric pathology characterized by dysfunctions in the frontal lobe of the brain, especially in planning, execution, and inhibition tasks, with an inability to make decisions and handle different sequences, also affecting the temporal lobe. The patient presents alterations to store, consolidate, and recall information. These neurocognitive deficits are accompanied by neurobehavioral disorders such as depression, anxiety, and apathy that contribute to the worsening of the quality of life, with a high impact on the individual, social, and family level. To identify the neurobehavioral disorders and neurocognitive deterioration that present a patient diagnosed with FTD: clinical case of low incidence and prevalence disease in Colombia. A 40-year-old man, with progressive deterioration of his immediate verbal memory, low verbal fluency, aberrant motor behavior, sexual impulsivity, alterations in his executive functions, especially in planning tasks, decision-making, and inhibition was found to have a lesser degree of affectation in his visuospatial functioning and visuoconstructive abilities. It was found that the patient presents a severe dysexecutive syndrome associated with a clinical picture of FTD, correlated with an inability to process and recall information, accompanied by disorders such as depression, anxiety, and apathy. It is necessary to generate a functional neurorehabilitation plan that aims to improve the quality of life in these patients. In the same way, it is necessary to create new lines of research and intervention that have the purpose to create a greater field of heuristics or new questions in this type of neurodegenerative pathologies. [ABSTRACT FROM AUTHOR]

The increased use of immune-checkpoint inhibitors to treat various types of cancer has increased the incidence of immune-related adverse events (irAEs). Hepatic irAEs are frequent and can lead to serious conditions. Among the various types of hepatic irAEs reported to date, bile duct injury has been shown refractory to steroid treatment. This study describes 2 patients with hepatic irAEs manifesting as intrahepatic bile duct injury. Immunostaining with antibodies to both CD8 and cytokeratin-7 was useful for the diagnosis, and both patients were refractory to steroid treatment. Prompt diagnosis and active immunosuppressive therapies are required in such cases. [ABSTRACT FROM AUTHOR]

Introduction: BK virus (BKV) infection in renal transplant (RT) recipients can cause hemorrhagic cystitis, transient renal dysfunction, and BKV nephropathy (BKVN). The prevalence and significance of BKV in RT recipients remain to be clarified in the Iranian population. The purpose of this review is to summarize the overall prevalence of BKV infection in RT recipients from previously published studies in Iran. Methods: We systematically reviewed articles through a comprehensive search of the main electronic and Persian national databases up to November 2019. Results: The overall pooled prevalence of BKV infection among the Iranian population was 23% (95% CI; 15–33%). Comparing these studies revealed that the prevalence of BKV in plasma samples ranges from 3 to 40%, in renal biopsies 1–13%, and in urine samples 10–49%. Due to substantial heterogeneity among reported studies (I2 = 93%, p < 0.01), random-effect meta-analysis was performed. BKV infection rate was slightly higher in women than men (16%, p = 0.04 vs. 14%, p < 0.01, respectively). The majority of the studies employed real-time PCR (24%, I2 = 93, p < 0.01) and analyzed plasma samples alone or in combination with other types of specimens. BKV prevalence from 5 cities among the Iranian population showed a higher prevalence rate in Guilan. Conclusion: Our analysis provides a preliminary estimate of the epidemiology of BKV infection in RT recipients in Iran. These results arouse a need for more epidemiological studies of BKV infection in different unanalyzed regions in Iran. Early detection of BKV in RT recipients helps timely nephropathy diagnosis and prevents graft loss. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a clinically heterogeneous disease, with chameleon presentations and several mimics. Considering the poor prognosis of ALS, their precise and timely identification is pivotal. Affection of the cervical spine represents one potential source of ALS mimics that should never be missed, since it is potentially treatable. We hereby present 5 cases initially diagnosed as ALS but eventually found to have different kinds of cervical spine affection, from a common compressive myelopathy to a rare space-occupying cystic fluid collection. [ABSTRACT FROM AUTHOR]

Background: Primary liver cancer, around 90% are hepatocellular carcinoma in China, is the fourth most common malignancy and the second leading cause of tumor-related death, thereby posing a significant threat to the life and health of the Chinese people. Summary: Since the publication of Guidelines for Diagnosis and Treatment of Primary Liver Cancer (2017 Edition) in 2018, additional high-quality evidence has emerged with relevance to the diagnosis, staging, and treatment of liver cancer in and outside China that requires the guidelines to be updated. The new edition (2019 Edition) was written by more than 70 experts in the field of liver cancer in China. They reflect the real-world situation in China regarding diagnosing and treating liver cancer in recent years. Key Messages: Most importantly, the new guidelines were endorsed and promulgated by the Bureau of Medical Administration of the National Health Commission of the People's Republic of China in December 2019. [ABSTRACT FROM AUTHOR]

Trichoblastomas (TBs) are extremely rare, benign hair germ tumors that can mimic basal cell carcinoma (BCC). They usually arise on the head or neck and have a potential for malignant transformation, albeit it is rare. We report a case of giant TB on the forehead of a 75-year-old otherwise healthy woman. Since the age of 20 she reported a bulge on her forehead, in which a superficial-looking wound had now developed. Initially a dermatologist biopsied the tumor suspecting a BCC, which the histological analyses confirmed. The patient was then referred to the Department of Plastic Surgery for complete excision of the carcinoma, including the large frontal bulge. Surprisingly, the concluding pathology report changed the diagnosis from a BCC to a TB. Current management of most skin lesions relies on the histopathological subtype of a single punch biopsy. Many benign and malignant dermatological entities may mimic BCC, and therefore misdiagnosis can lead to either unnecessary excision or delayed treatment of metastatic disease. Mimics may include various types of nonneoplastic processes, benign adnexal tumors, including TB, or cutaneous carcinomas with basaloid features. A single punch biopsy is not always adequate in making the correct diagnosis. Although it is considered the gold standard, the clinical assessment is just as important. Due to its potential for malignant transformation, it is recommended to excise TB with negative margins. [ABSTRACT FROM AUTHOR]

This case report describes the unusual presentation of a globe subluxation following long-term high-dose oral steroid treatment for myasthenia gravis (MG). The patient presented initially with fluctuating vertical diplopia. Auto-antibodies against the acetylcholine receptor were weakly positive, confirming the diagnosis of MG. After initial treatment with pyridostigmine, the disease evolved to generalized MG. Plasmapheresis and high-dose steroids were started subsequently. As a side effect of this treatment the patient gained about 30 kg in weight and developed steroid myopathy and a prominent cushingoid facies with bilateral exophthalmos. A year after his initial diagnosis he experienced a spontaneous globe subluxation on the left eye. He was able to immediately reposition the globe manually himself. Four months later a new subluxation occurred. Because of these aforementioned severe side effects of the steroid treatment, the methylprednisolone was tapered and replaced by tacrolimus. After about 6 weeks the patient went into remission. We believe, that the spontaneous globe subluxations were caused by a weakness of the extraocular muscles in combination with a significant gain of intraorbital fat tissue, both induced by cumulative, excessive steroids. Steroids are often necessary in the treatment of MG; however, most of the time a high dose of 64 mg is not needed for ocular MG and especially the continuation of a dose of 58 mg or more for a long period is not recommended. Careful follow-up is obligatory to timely recognize side effects. In case of severe side effects or the need for long-term treatment, the use of other immunosuppressive therapies should be considered. Extra care and caution is recommended in patients who are anatomically predisposed with proptosis. [ABSTRACT FROM AUTHOR]

Bowen's disease is a squamous cell carcinoma in situ that commonly develops on the trunk, arms, or legs and has not spread beyond the top layer of skin. It seldom develops on the nipple. We report a patient who presented with Bowen's disease of the nipple and had a concurrent breast cancer identified in the ipsilateral breast after careful examination. Histopathological examination of the surgical specimen after mastectomy confirmed the diagnoses. [ABSTRACT FROM AUTHOR]

Tumor lysis syndrome (TLS) is a hemato-oncological emergency characterized by metabolic and electrolyte imbalances which are associated with disintegrating tumor cells. The syndrome is frequently observed when starting cytotoxic treatment of hematological malignancies, while the incidence of spontaneous tumor lysis prior to the start of tumor therapy is rare. Here, we present a case of spontaneous TLS in a male patient who was referred with unspecific symptoms and suspected metastatic malignancy. He developed acute renal failure before the diagnosis of a high-grade B-cell lymphoma (double hit lymphoma) and start of therapy. Although the course of TLS would have required intensive care, the patient rejected such treatment for personal reasons and died soon after the discontinuation of therapy. The case emphasizes the life-saving relevance of early detection and appropriate treatment of TLS. It also demonstrates the importance of actively screening for TLS, primarily in patients with malignant diseases and high tumor load, even if they are not receiving cytotoxic therapy. [ABSTRACT FROM AUTHOR]

Although ovarian cancer often presents as a widespread disease, metastases to the breast and/or axillary lymph nodes are a very rare event, accounting for only 0.03–0.6% of all breast cancers. Its early recognition and accurate distinction from primary breast cancer are of crucial importance to choose an adequate systemic therapy over unnecessary surgeries. We presented the case of a 53-year-old woman who was diagnosed with breast metastases 2 years after the diagnosis of advanced primary serous ovarian cancer. The patient underwent primary cytoreductive surgery and platinum-based chemotherapy in combination with bevacizumab, followed by bevacizumab maintenance for 18 months. After 2 years of negative follow-ups, the disease unexpectedly spread to the left breast and axillary lymph nodes. No axillary lymph node dissection or breast surgery was performed. The patient received axillary radiotherapy and multiple chemotherapy lines: gemcitabine/cisplatin, liposomal doxorubicin, topotecan, olaparib/cediranib, paclitaxel, and cisplatin. Unfortunately, none of these treatments improved her prognosis and she died 3 years after the disease recurrence. Ovarian cancer metastasis to the breast reveals a disseminated disease with a poor prognosis. Currently, no valid treatment options are available as the disease shows multidrug chemoresistance. In the era of precision medicine, the characterization of genetic and molecular markers may play a role in offering new promising targeted therapies. [ABSTRACT FROM AUTHOR]

Pseudoachalasia, also known as secondary achalasia, is a rare clinical condition mimicking idiopathic achalasia but unrelated to primary loss of nitrergic innervation. It has mostly been attributed to malignancy infiltrating the oesophageal wall, but several other benign underlying pathologies have been reported. Because of similar manometric appearance, high-resolution manometry (HRM) of the oesophagus alone cannot distinguish between idiopathic achalasia and pseudoachalasia. Misdiagnosis can result in ineffective treatment by dilatation or even more invasive therapy. This is the first case-report of pseudoachalasia secondary to oesophageal deviation resulting from mediastinal shift and left atrial enlargement following prior left lower lobectomy. HRM, the gold standard for the diagnosis of achalasia, confirmed the incomplete relaxation of the lower oesophageal sphincter (LES) in absence of normal oesophageal peristalsis. However, additional workup with CAT scan and cardiac ultrasound identified an anatomical shift by the extrinsic mass effect resulting from the atrial enlargement, but without contrast retention at the LES. [ABSTRACT FROM AUTHOR]

Background: Iron deficiency (ID) and ID anemia (IDA) are common in the member states of the Gulf Cooperation Council (GCC). The unique genetic and lifestyle factors of the patient population in the region have necessitated the development of recommendations to help educate health-care professionals on appropriate diagnosis and management of ID/IDA.Methods: A panel of regional experts, including gastroenterologists and hematologists with expertise in the treatment of IDA, was convened to develop regional practice recommendations for ID/IDA. After reviewing the regional and international literature, the expert panel developed consensus recommendations for screening, diagnosis, and treatment of patients with IDA in the GCC region.Results: The recommendations proposed were customized to the patient population keeping in view the increasingly recognized burden of coeliac disease, high fertility and obesity rates, high prevalence of alpha- and beta-thalassemia traits, and poor tolerance and low treatment compliance with oral iron therapy.Conclusions: This consensus statement proposes recommendations for screening, diagnosis, and treatment of IDA in the GCC region. [ABSTRACT FROM AUTHOR]

Objective: In this retrospective single institution study, we investigated the clinicopathologic features and treatment characteristics of 90 patients with congenital corneal opacities (CCO) (117 eyes) who were 3 years and younger and treated at our hospital.Subject and Methods: We reviewed the clinical data of patients with CCO who presented for the first time for treatment at our hospital between January 1, 2017, and December 31, 2017. CCO were classified using the "STUMPED" (Sclerocornea, Tears in Descement's membrane, Metabolic, Peters, Endothelial dystrophy and Dermoid) method and confirmed by pathological examination. -Results: Seventy percent of the patients had unilateral CCO. Iridocorneal adhesions (61 eyes, 52.1%) and cataracts (22 eyes, 18.8%) were the 2 most common ocular abnormalities. Systemic abnormalities were present in 5 patients (5.6%), including growth retardation (4 patients) and congenital brain defects (1 patient). Eighty-five eyes (72.6%) underwent penetrating keratoplasty (PK), and lamellar keratoplasty (LK) was performed in 30 (25.6%) eyes. Forty-seven (95.9%) eyes with Peters anomaly and all 16 eyes with sclerocornea received PK, and all 24 eyes with dermoids were treated with LK.Conclusion: Our study demonstrates that CCO has varied manifestations in infants and young children in China. A thorough medical history, careful clinical examination, and the use of accessory examinations such as ultrasound biomicroscopy are critical for the accurate diagnosis and classification of CCO and to provide guidance on therapeutic choices. [ABSTRACT FROM AUTHOR]

Background: Gastrointestinal stromal tumors occur frequently. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is performed commonly for diagnosis. However, the success rate of histological diagnosis is insufficient when the submucosal tumor (SMT) is small. Recently, another technique, mucosal cutting biopsy (MCB) has been reported. The aim of this study is to evaluate the efficacy and safety of MCB. Method: Between January 2012 and August 2018, MCB and EUS-FNA were performed 16 and 31 times for diagnosing gastric SMT. The diagnostic rate, the rate of successful immunohistochemistry, and the safety were reviewed. Difficult locations for EUS-FNA were also evaluated. Results: The mean SMT sizes measured on MCB and EUS-FNA were 21.2 and 36.2 mm. The diagnostic rates of MCB and EUS-FNA were almost the same (88 vs. 81%), but successful immunohistochemistry was significantly higher in the MCB group (93 vs. 59%, p = 0.03). In the subgroup of SMTs < 20 mm, the successful histological diagnosis rate from EUS-FNA was relatively low. There were no complications. Failures of EUS-FNA were more frequent in the middle third of the stomach. Conclusions: MCB was an effective procedure for diagnosing gastric SMT, especially in the case of small SMTs located at the middle third of the stomach. [ABSTRACT FROM AUTHOR]

Background/Aims: Colorectal cancer (CRC) is the third most commonly diagnosed malignancy and the second leading cause of cancer-related deaths worldwide. Thus, methods for early diagnosis of CRC are urgently needed. We aimed to identify potential long non-coding RNAs (lncRNAs) in circulatory exosomes that may serve as biomarkers for the detection of early-stage CRC. Methods: Exosomes from the plasma of CRC patients (n = 50) and healthy individuals (n = 50) were isolated by ultracentrifugation, followed by extraction of total exosomal RNAs using TRIzol reagent. Microarray analysis was used for exosomal lncRNA profiling in the two groups, and real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to determine the expression level of lncRNAs in all patients and healthy subjects. Results: The expression of six lncRNAs (LNCV6_116109, LNCV6_98390, LNCV6_38772, LNCV_108266, LNCV6_84003, and LNCV6_98602) was found to be significantly up-regulated in CRC patients compared with that in healthy individuals by qRT-PCR. The receiver operating characteristic curve was used to verify their diagnostic accuracy. The values of the area under the curve for these lncRNAs were 0.770 (LNCV6_116109), 0.7500 (LNCV6_98390), 0.6500 (LNCV6_38772), 0.6900 (LNCV_108266), 0.7500 (LNCV6_84003), and 0.7200 (LNCV6_98602). Conclusion: Our study suggested that the expression of these six exosomal lncRNAs (LNCV6_116109, LNCV6_98390, LNCV6_38772, LNCV_108266, LNCV6_84003, and LNCV6_98602) was significantly up-regulated in the plasma of CRC patients, and that they may serve as potential non-invasive biomarkers for early diagnosis of CRC. [ABSTRACT FROM AUTHOR]

Background/Aims: This study presents an analysis of the sonographic and laboratory parameters of solitary kidney in Wilms tumour survivors (TWs) and compares these parameters with those of healthy individuals. Methods: Fifty-three TWs who completed treatment for Wilms tumour and 44 healthy individuals were enrolled. The study protocol consisted of completing a medical history, sonographic examination of the solitary kidney, estimation of glomerular filtration rate (eGFR) by the Schwartz or MDRD formulas, albumin urine excretion and BP measurement. Results: Sonographic signs of kidney damage were observed in 22 (41,5%) TWs. The most frequently detected abnormalities are hyperechoic rings around renal pyramids (28,3% TWs). Hypertrophy of the solitary kidney occurred in 71,7% of cases. The mean volume of the solitary kidney was 77% of the sum of the two kidney volumes in the control group. The median eGFR in the TWs group was 117 with 25Q-105,5, 75Q-130 ml/min/1,73 m2 vs 131,8 with 25Q-124, 75Q-140 ml/min/1,73 m2 in the control group (p=0,000). Six TWs (11,3%) had a value of eGFR below 90 ml/min/1,73 m2. Increased urine albumin excretion (> 30 mg/g) was observed in 7 TWs (13,2%) and in 3 (6,8%) individuals in the control group. Conclusion: Ultrasonographic abnormalities in solitary kidney of TWs are frequent. The most frequently detected abnormalities are hyperechoic rings around renal pyramids. Sonographic examination of TWs ought to be performed not only to detect tumour recurrence but also to assess the signs of kidney damage and their progression. [ABSTRACT FROM AUTHOR]

Background/Aims: Kidney renal clear cell carcinoma (KIRC) is one of the most fatal malignancies due to late diagnosis and poor treatment. To improve its prognosis, a screening for molecular biomarkers of KIRC is urgently needed. Long non-coding RNAs (lncRNAs) play important roles in tumorigenesis and prognosis of cancers. However, it is not clear whether lncRNAs can be used as molecular biomarkers in predicting the survival of KIRC patients. Methods: In this study, our aim was to identify lncRNAs/mRNAs signatures and their prognostic values in KIRC. The aberrant expression profile of mRNAs and lncRNAs in 529 KIRC tissues and 72 adjacent non-tumor pancreatic tissues were obtained from the Cancer Genome Atlas (TCGA). A weighted gene co-expression network analysis (WGCNA) of two key lncRNAs was constructed. We constructed an aberrant lncRNA-mRNA-miRNA ceRNA network in CESC. In addition, Gene Ontology (GO) and KEGG pathway analysis were performed. Results: Using lncRNA/mRNA expression profiling data, the overall analysis revealed that two novel lncRNA signatures (DNM1P35 and MIR155HG) and several mRNAs were found to be significantly correlated with KIRC patient's overall analysis. Based on the target gene of the two lncRNA in co-expression network, the GO and KEGG analysis were also performed. A dysregulated lncRNA-related ceRNA network was also observed. Conclusion: These results suggested that the two novel lncRNAs signatures may act as independent prognostic biomarkers for predicting the survival of KIRC patient. [ABSTRACT FROM AUTHOR]

Objective: This study assessed whether or not a simple biochemical parameter, serum thyrotropin (TSH), within the reference range can predict the likelihood of thyroid malignancy in subjects undergoing fine-needle aspiration biopsy (FNAB) for thyroid nodules.Subjects and Methods: This cross-sectional study evaluated 236 patients without overt thyroid dysfunction who were not on levothyroxine therapy. They underwent FNAB of the thyroid nodules at the Clementino Fraga Filho University Hospital between 2011 and 2012. The reference range and serum TSH quartiles were determined according to age-specific values for serum TSH and then compared between the cases with benign thyroid nodular disease and differentiated thyroid carcinoma (DTC) based on surgical pathology reports.Results: Of the 236 patients, 201 (85.1%) underwent a surgical procedure (thyroidectomy) and 89/236 (44.3%) had DTC. The mean TSH concentrations were 2.09 ± 1.15 mU/L in benign patients versus 2.73 ± 1.33 mU/L in cases of DTC (p < 0.01). As TSH increased from quartiles 1 to 4, the frequency of a malignant diagnosis also increased progressively from 22% in quartile 1 to 65% in the last quartile (p ≤ 0.001).Conclusion: Thyrotropin levels were positively associated with the diagnosis of DTC in thyroid nodules. [ABSTRACT FROM AUTHOR]

Background/Aims: Unlike other organs, which only have one set of capillary network, the renal microvasculature consists of two sets of capillary network series connected by efferent arterioles. Angiotensin II constricts the efferent glomerular artery. Hence, renal tumor blood flow (BF) distribution may be different from tumors in other organs. This study aims to investigate the effects of angiotensin II on the hemodynamics of intrarenal VX2 tumors using perfusion computed tomography(CT). Methods: Twenty-four male New Zealand white rabbits were randomly divided into three groups: groups A (blank controls), group B (negative controls), and group C (angiotensin II-treated animals). Group B and C were established to the model of intrarenal VX2 tumors. Furthermore, perfusion CT of the kidney was performed in each group. Prior to perfusion CT scan in group C, the mean arterial blood was elevated to 150-160 mmHg by angiotensin II. The BF, blood volume (BV), mean transit time (MTT), capillary permeabilitysurface area product (PS), and relative permeability-surface area product (RPS) of tumors and renal tissues were calculated. Results: Compared with normal renal cortex tissues in group A, the BF, BV and PS values of tumors in group B were significantly lower, MTT was prolonged and RPS increased. Compared with group B, only the RPS of these tumors increased from 83.23 ± 29.17% to 120.94 ± 31.84% by angiotensin II infusion. Angiotensin II significantly increased the RPS value of the renal cortex distant from the tumor (CDT) and the right renal cortex (RRC). Conclusions: Perfusion CT can accurately observe the influence of angiotensin II on normal and tumor BF in kidneys. This clarifies the effect of angiotensin II on intrarenal tumor hemodynamics. [ABSTRACT FROM AUTHOR]

Background/Aims: Since the function of microRNA (miR)-210 in non-small cell lung cancer (NSCLC) remains unclear, we aimed to explore the clinical significance of miR-210 in NSCLC. Methods: NSCLC-related data from 1673 samples on Gene Expression Omnibus and 1090 samples on The Cancer Genome Atlas were obtained and analyzed. The expression level of miR-210 was validated via real-time quantitative PCR analysis with 125 paired clinical samples. A meta-analysis was performed to generate a comprehensive understanding of miR-210 expression and its clinical significance in NSCLC. In addition, bioinformatics analysis was also conducted to reveal the potential underlying mechanism of miR-210 action in NSCLC. Results: miR-210 expression was consistently elevated in NSCLC solid tissue samples. However, its expression was controversial in easily obtained body fluids (i.e., blood, plasma, and serum). Moreover, an overall pooled meta-analysis implied a comparatively higher level of miR-210 expression in NSCLC cancerous tissue than in normal control tissue (P < 0.001). In addition, a meta-analysis of outcome revealed a significant diagnostic capacity of miR-210 in NSCLC by detecting its expression in serum and sputum (area under the summary receiver operating characteristic curve 0.82 and 0.81, respectively). miR-210 overexpression was associated with poor progression-free survival (PFS) in NSCLC and was negatively related to overall survival and disease-free survival. Bioinformatic gene enrichment and annotation analyses showed that the target genes of miR-210 were greatly enriched in cell adhesion and plasma membrane, and three pathways were considered to be the main functional circuits of miR-210: renin secretion, the cGMP-PKG signaling pathway, and cell adhesion molecules. Conclusion: In NSCLC, miR-210 expression was elevated and overexpression indicated poor PFS. Expression level of miR-210 in serum and sputum showed significant diagnostic value for NSCLC. [ABSTRACT FROM AUTHOR]

Background/Aims: The association between the genetic polymorphisms located in either the exon or untranslated region of MTHFR and the risk of human atherosclerosis has been welldocumented. This study analyzed MTHFR polymorphisms at the 3'-untranslated region for association with risk and outcome of atherosclerosis in a Chinese Han population. Methods: The hospital based case-control study was conducted with 500 patients and 600 healthy volunteers as control enrolled. The genotyping was conducted by using Taqman probe. The potential interaction was predicted by multiple bioinformatics analysis. The relative expression of MTHFR was detected by qRT-PCR. Further confirmation was determined by dual-luciferase assay. The plasma homocysteine levels were assayed by ELISA. Results: Cigarette smoking, alcohol consumption, diabetes, hypertension and low levels of serum high-density lipoprotein-C were associated with an increased risk of developing ischemic stroke. MTHFR rs915014 AG and GG genotypes were significantly associated with increased risk of rs915014 compared with the GG genotype. The qRT-PCR confirmed that MTHFR rs915014 AG or GG genotypes could facilitate miR-2861 binding leading to decreased MTHFR levels in cells. In addition, patients carrying the MTHFR rs915014 AG or GG genotypes were associated with accumulation of circulating tHcy volume and a poor atherosclerosis consequence. Conclusions: This study demonstrates that the MTHFR rs915014 is associated with increased risk of atherosclerosis and might be a shot term outcome biomarker for atherosclerosis patients. [ABSTRACT FROM AUTHOR]

Background/Aims: Circular RNAs (circRNAs), a novel class of noncoding RNAs, have been found to be dysregulated in various cancers. However, the clinical application value of these circRNAs in digestive system cancers remains to be clarified. We aimed to comprehensively explore the potential role of circRNAs as diagnostic indicators in digestive system malignancies. Methods: Relevant studies were systematically retrieved from PubMed, Web of Science and the Cochrane Library. The data that were required to complete 2 × 2 contingency tables were obtained from the included studies. Stratified analyses by cancer type, sample size and publication year were performed. Results: Thirteen studies with 2,276 individuals were included in the meta-analysis. The pooled sensitivity and specificity of circRNAs in the diagnosis of digestive system malignancy were 0.72 [95% confidence interval (CI): 0.65-0.77] and 0.77 (95% CI: 0.72-0.81), respectively. The overall positive likelihood ratio was 3.09 (95% CI: 2.64-3.62), and the overall negative likelihood ratio was 0.37 (95% CI: 0.31-0.44). The pooled diagnostic odds ratio was 8.38 (95% CI: 6.86-10.25), and the overall area under the curve was 0.81 (95% CI: 0.77-0.84), indicating good discriminative ability of circRNAs as biomarkers for digestive system malignancy. Conclusion: circRNAs distinguish patients with digestive system cancer from controls with relatively high diagnostic accuracy. circRNAs may be used as potential biomarkers for the diagnosis of digestive system malignancy. [ABSTRACT FROM AUTHOR]

Background/Aims: Diffuse large B-cell lymphoma (DLBCL) is an aggressive disease, and is the most common type of lymphoma in adults. Although significant progress in treatment has been made using chemotherapy combinations, there exist a large amount of relapse or refractory cases. Thus, effective clinical biomarkers for DLBCL are urgently needed. Our study aims to explore the predictive significance of using the immune response to tumor burden ratio [defined as the lymphocyte to monocyte ratio (LMR)/lactate dehydrogenase (LDH) levels] in 184 DLBCL patients and the potential mechanism underlying the use of the LMR to tumor burden ratio in predicting patient survival. Methods: The correlation between serum LDH levels and tumor levels assessed by PET-CT was determined using Spearman's correlation analysis. Clinical data from 184 DLBCL patients was assessed using receiver operating characteristic curve analysis and survival analysis. The potential correlation between tumor burden and lymphocytes or monocytes was analyzed by immunohistochemical staining, flow cytometry, and ELISA analysis of patient samples. In addition, we performed in vitro studies to further determine the effects of tumor burden on the anti-tumor activity of T lymphocytes. Results: We observed that serum LDH was an excellent surrogate marker of tumor burden in DLBCL patients, and that the ratio of LMR to LDH was an independent prognostic biomarker capable of predicting survival in DLBCL patients. Further analysis showed that a high tumor burden was correlated with decreased Ki67 expression in T cells, either in the solid tumor tissue or in the circulating blood. In addition, based on an in vitro co-culture study, a higher tumor burden led to the suppression of the anti-tumor response of T cells. Furthermore, we found that a higher tumor burden was correlated with the differentiation of monocytes to tumor associated macrophages in the tumor micro-environment. Both results demonstrate the importance of considering both the immune system and tumor burden for prognostic analysis. Conclusion: Our study has identified a novel clinical biomarker, namely, the immune response to tumor burden ratio, that can be used to distinguish survival outcomes in DLBCL patients, and demonstrated the potential mechanism underlying the use of this biomarker, that incorporates both the immune system and tumor burden, for use in future clinical applications. [ABSTRACT FROM AUTHOR]

Background/Aims: Circular RNAs (circRNAs), a novel class of noncoding RNAs, have been found to be dysregulated in various cancers. However, the clinical application value of these circRNAs in digestive system cancers remains to be clarified. We aimed to comprehensively explore the potential role of circRNAs as diagnostic indicators in digestive system malignancies. Methods: Relevant studies were systematically retrieved from PubMed, Web of Science and the Cochrane Library. The data that were required to complete 2 × 2 contingency tables were obtained from the included studies. Stratified analyses by cancer type, sample size and publication year were performed. Results: Thirteen studies with 2,276 individuals were included in the meta-analysis. The pooled sensitivity and specificity of circRNAs in the diagnosis of digestive system malignancy were 0.72 [95% confidence interval (CI): 0.65-0.77] and 0.77 (95% CI: 0.72-0.81), respectively. The overall positive likelihood ratio was 3.09 (95% CI: 2.64-3.62), and the overall negative likelihood ratio was 0.37 (95% CI: 0.31-0.44). The pooled diagnostic odds ratio was 8.38 (95% CI: 6.86-10.25), and the overall area under the curve was 0.81 (95% CI: 0.77-0.84), indicating good discriminative ability of circRNAs as biomarkers for digestive system malignancy. Conclusion: circRNAs distinguish patients with digestive system cancer from controls with relatively high diagnostic accuracy. circRNAs may be used as potential biomarkers for the diagnosis of digestive system malignancy. [ABSTRACT FROM AUTHOR]