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Glioblastoma (GBM) is a fatal human brain tumor of grade IV/4 by WHO classification, with a very poor prognosis. At the molecular level and clinical, GBM has at least two types, primary and secondary. Each has a different tumorigenesis and clinical presentation. In this chapter, some major molecular biomarkers and diagnostic hallmarks of GBM will be reviewed and discussed.

Background: Multifocal hepatocellular carcinoma (MF-HCC) accounts for >40% of HCCs, demonstrating a poor prognosis than single primary HCCs. Characterizing the dynamic changes of mutation signature along with clonal evolution, quantifying intrahepatic metastatic timing, and investigating the genetic structure in the preneoplastic stage underlying different subtypes of MF-HCC are important for understanding their molecular evolution and developing a precision management strategy. Methods: We conducted whole-exome sequencing in 74 tumor samples from spatially distinct regions in 35 resected tumor lesions and adjacent non-cancerous tissues in 11 patients with synchronous MF-HCCs, 15 histologically confirmed preneoplastic lesions and six samples from peripheral blood mononuclear cell. We also used the previously published MF-HCC cohorts (n=9) as an independent validation dataset. Results: We classified MF-HCCs into three subtypes, including intrahepatic metastasis, multicentric occurrence, and mixed intrahepatic metastasis and multicentric occurrence. The dynamic changes in mutation signatures between tumor subclonal expansions demonstrated varied etiologies underlying the clonal progression in different MF-HCC subtypes, especially the contribution of aristolochic acid exposure decreased along with subclonal expansions. The clonal evolution in intrahepatic metastasis exhibited an early metastatic seeding that occurred at 10-4–0.01 cm3 in primary tumor volume, below the limitation in clinical detection. These findings were validated in another independent cohort. In addition, for multicentric occurrence MF-HCC, mutational footprints in the preneoplastic lesions revealed common preneoplastic arising clones, evidently being ancestors of different tumor sites. Conclusion: Our study comprehensively characterized the dynamic mutational signature, early metastatic timing, and common preneoplastic clones in multicentric occurrence that characterized the varied tumor clonal evolutionary history underlying different subtypes of MF-HCC, and provided important implications for optimizing personalized clinical management for MF-HCC.

Objective The clinical significance of the YY1 gene mutation and expression in pancreatic neuroendocrine tumors (PNETs) remains unknown. Therefore, this study aimed to comprehensively analyze the somatic mutation of YY1 in the different subtypes of PNETs. Methods A total of 143 PNETs were assessed by Sanger sequencing to identify the somatic mutation of YY1 gene in various subtypes of PNETs. YY1 protein expression was examined in 103 PNETs by immunohistochemical staining and western blot. Gene mutation and its protein expression were correlated with clinicopathologic features. Results A recurrent mutation (chr14:100743807C>G) in the YY1 gene was identified in 15 of 83 insulinomas (18%) and in only 1 of 60 noninsulinoma PNETs (1.7%) (P = .0045). The YY1 mutation was not found in MEN1-associated insulinomas. The YY1 mutation in insulinomas was correlated with older age and lower serum glucose levels (age, 57 vs 42.5 years, P = .006; blood glucose, 25.2 vs 33.6 mg/dL, P = .008). YY1 protein expression was found in 100 of 103 PNETs, although expression was weaker in metastases than in localized tumors (P = .036). The stronger expression of YY1 protein was associated with favorable disease-free survival of patients with PNETs (log-rank, P = .011; n = 70). Multivariable statistical analysis showed that YY1 protein expression could be an independent predictor of prognosis. Conclusion The hotspot YY1 mutation mostly occurred in insulinomas and rarely in noninsulinoma PNETs. The stronger YY1 protein expression was correlated with the better prognosis of PNETs patients.

Temporal lobe epilepsy (TLE) is the most common form of adult epilepsy, frequently accompanied with cognitive deficits. The present study aims to investigate functional network alterations affected by cognitive impairments in drug-resistant TLE. Patients with drug-resistant TLE were divided into normal cognition (NC) and abnormal cognition (AC) groups based on their primary medical history and completed the Wechsler intelligence scale. Thirty-one patients in the NC group and 30 in the AC group had mean intelligence quotients (IQ) of 107 (96-137) and 71 (60-85), respectively. Eighteen controls were enrolled in the study. Graph theory analysis showed decreased alpha small world index (SWI) in the AC group compared to that in the NC group and controls. Increased SWI in the fast rhythm was observed in both TLE groups compared with controls. But the gamma SWI in the AC group declined and was significantly lower than in the NC group at 50–70 Hz. A lower IQ is associated with a decreased SWI in alpha and 50-70Hz. Spectral analysis revealed reduced alpha power and increased delta power in the TLE groups compared to the controls. Immunofluorescence analysis revealed more severe amyloid-β (Aβ) and phosphorylated Tau (p-Tau) loads in the resected hippocampus of the AC group than that of NC group. Cognitive deficits in drug-resistant TLE are associated with general EEG activity slowing, loss of efficiency in gamma connectivity, and increased Aβ and p-Tau expression. These alterations are potential markers and intervention targets for concomitant cognitive decline in drug-resistant epilepsy.

Background Ectopic adrenocortical tissue is a lesion usually found incidentally during autopsy or inguinal surgery. Here, we demonstrate an extremely unusual case of intrahepatic adrenocortical adenoma which highly mimicks hepatocellular carcinoma (HCC) and brings challenges for clinicians and pathologists. The diagnostic pitfalls have been discussed in detail to provide clues for guiding differential diagnosis and future treatment. Case presentation A 44-year-old man was admitted into our hospital for evaluation of a hepatic mass identified during routine examination. Enhanced CT revealed its margin displayed apparent enhancement in arterial phase, but hypointensity in portal and delayed phase. HCC was suspected and partial hepatectomy was performed. Microscopically, cells were arranged in solid sheets. Most of the tumor cells were large, polygonal, had prominent nucleoli and were rich in eosinophilic cytoplasm. Pleomorphic nucleus was frequently found. Focally, smaller cells were found with small nuclei and granular cytoplasm. Immunohistochemically, tumor cells were negative for Arg-1, glypican-3 (GPC3), hepatocyte specific antigen (HSA), and positive for synaptophysin (Syn), α-inhibin, and Melan A. The Ki-67 index was 1 %. The final diagnosis was ectopic adrenocortical oncocytic adenoma and the patient was uneventful after the surgery. Conclusion Intrahepatic adrenocortical adenoma in the liver can hardly be diagnosed through radiology and little experience in pathology has been reported. In the present case, massive oncocytic changes and huge pleomorphism add greatly to the difficulties of making correct diagnosis. This lesion should be carefully kept in mind and a combination of markers is suggested for differentiating from HCC.

Background Sellar lesions with central diabetes insipidus have a wide range of causes, and diagnosis is relatively difficult. The indication and clinical value of biopsy are still controversial. Objective To describe the etiology, demographic characteristics, manifestations, laboratory tests and imaging findings of this disease and to explore the clinical value and safety of endoscopic transsphenoidal biopsy. Methods Retrospective analysis of 124 patients with sellar lesions and central diabetes insipidus who underwent endoscopic transsphenoidal biopsy at the Neurosurgery Department, Peking Union Medical College Hospital, from 2011 to 2019. Results The main etiology includes congenital diseases, inflammatory/infectious diseases and tumor diseases. The most common diseases were germ cell tumors, Langerhans cell histiocytosis, lymphocytic hypophysitis, and Rathke's cleft cysts. Except for the age at the time of biopsy of patients with tumor diseases, which was significantly lower than that of the other two, the other clinical manifestations of the three types of diseases were not significantly different. Among the 124 patients, biopsy was performed via an endoscopic transsphenoidal approach for 101 with intrasellarly available lesions or via an endoscopic extended transsphenoidal approach for 23 with intrasellarly unavailable lesions. 6 patients had central nervous system infections after surgery, and 3 had cerebrospinal fluid rhinorrhea, of which 2 were surgically repaired. These incidences were basically the same as those of classic surgery. 2 patients had worse visual acuity, 2 had worse visual field, and 2 had worse eye movement. Excepting one patient, all of whom have recovered after treatment. Conclusions Noninvasive examination is difficult for identifying the common causes of this type of disease. Endoscopic transsphenoidal biopsy is relatively safe and effective, helps doctors to select the best treatment for patients, and is worth promoting.

BACKGROUND: Cardiovascular involvement manifesting as arrhythmias has been confirmed in patients with coronavirus disease 2019 (COVID-19), so we aimed to explore the association between primary tachyarrhythmia and death in critically ill patients with COVID-19 in this retrospective study. METHODS: A total of 79 critically ill patients with COVID-19 were included. Demographic characteristics, clinical data (past history, vital signs, therapeutic management, and outcomes), and results of laboratory findings and cardiac investigations were collected. All statistical analyses were performed using SPSS 23.0 software (IBM, Armonk, NY, USA). RESULTS: The median age was 65±12 years, and 53 patients (67%) were male. A total of 57 (72%) patients died, and compared with survivors, these patients were older and had significantly higher Acute Physiology and Chronic Health Evaluation (APACHE) II score, Sequential Organ Failure Assessment (SOFA) score and fewer lymphocytes as well as higher heart rate (P

Background: The objective was to explore the discordance in the expression of the estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 between primary and recurrent/metastatic lesions in patients with early stage breast cancer as well as the prognostic impact.Method: Patients with early-stage primary breast cancer and confirmed recurrence/metastasis at Peking Union Medical College Hospital between January 2005 and August 2018 were screened. The details of discordance in each parameter between primary and recurrent/metastatic lesions and progression were recorded. Regression and survival analysis were applied to determine the association and clinical impact of the discordance.Results: We evaluated 75 patients. The discordance rate of ER, PR, HER2, and Ki-67 expression was 9.3, 14.7, 14.7, and 21.5%, respectively. Additionally, 66.7, 11.8, 14.3, and 0% of patients with Luminal A, Luminal B, HER2, and triple-negative primary tumors presented with a different subtype for the recurrent/metastatic tumors, respectively. No statistical difference in progression-free survival was observed according to the subtype of the recurrent or metastatic breast cancer (p > 0.05). Among 69 patients for whom treatment was adjusted after recurrence or metastasis, 66 patients remained recurrence-free during the follow-up period.Conclusion: For patients with early-stage breast cancer, the ER, PR, HER2, and Ki-67 expression profile for recurrent/metastatic tumors does not always match that of the primary tumor. After adjusting treatment according to the receptor expression in recurrent/metastatic lesions, most patients remained progression-free during the follow-up period.

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Isocitrate dehydrogenase (IDH) mutation, telomerase reverse transcriptase (TERT) promoter mutation and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status are diagnostic, prognostic, predictive and therapeutic biomarkers for primary diffuse gliomas, and this study aimed to explore the relationship between choline (CHO) positron emission tomography (PET) parameters and these molecular alterations. Twenty-eight patients who were histopathologically diagnosed with primary diffuse glioma and underwent presurgical CHO PET/CT were retrospectively analyzed, and IDH, TERT and MGMT alterations were examined. The volume of interest (VOI) was semiautomatically defined based on standardized uptake value (SUV) thresholds, and 5 traditional CHO parameters, namely, SUVmax, SUVmean, metabolic tumor volume (MTV), total lesion CHO uptake (TLC) and tumor-to-normal contralateral cortex activity ratio (T/N ratio), were calculated. Wilcoxon rank-sum tests and receiver operating characteristic (ROC) curves were applied to evaluate the differences and performances of the CHO parameters, and their capability to stratify patient prognosis was also evaluated. All 5 parameters were significantly higher in IDH-wildtype gliomas than in IDH-mutant gliomas (p = 0.0001–0.037), and SUVmax, SUVmean, TLC and the T/N ratio exhibited good performances in distinguishing the IDH status (areas under the ROC curve (AUCs) 0.856–0.918, accuracies 0.857–0.893) as well as stratifying patient prognosis. Although the differences and performances of the traditional parameters in distinguishing diverse TERT and MGMT statuses were moderate in the whole population, the T/N ratio and TLC displayed certain predictive value in discriminating the TERT status in the IDH-mutant and IDH-wildtype subgroups (p = 0.028–0.048, AUCs 0.857–0.860, accuracies 0.800–0.917, respectively). Traditional CHO PET parameters are capable of distinguishing IDH but not TERT or MGMT alterations in the whole population. In accordance with the clinical understanding of TERT promoter mutations, the T/N ratio and TLC can also discriminate the TERT status in IDH subgroups.

Objective: Chromosomal 1p/19q co-deletion is recognized as a diagnostic, prognostic, and predictive biomarker in lower grade glioma (LGG). This study aims to construct a radiomics signature to non-invasively predict the 1p/19q co-deletion status in LGG. Methods: Ninety-six patients with pathology-confirmed LGG were retrospectively included and randomly assigned into training (n = 78) and validation (n = 18) dataset. Three-dimensional contrast-enhanced T1 (3D-CE-T1)-weighted magnetic resonance (MR) images and T2-weighted MR images were acquired, and simulated-conventional contrast-enhanced T1 (SC-CE-T1)-weighted images were generated. One hundred and seven shape, first-order, and texture radiomics features were extracted from each imaging modality and selected using the least absolute shrinkage and selection operator on the training dataset. A 3D-radiomics signature based on 3D-CE-T1 and T2-weighted features and a simulated-conventional (SC) radiomics signature based on SC-CE-T1 and T2-weighted features were established using random forest. The radiomics signatures were validated independently and evaluated using receiver operating characteristic (ROC) curves. Tumors with IDH mutations were also separately assessed. Results: Four radiomics features were selected to construct the 3D-radiomics signature and displayed accuracies of 0.897 and 0.833, areas under the ROC curves (AUCs) of 0.940 and 0.889 in the training and validation datasets, respectively. The SC-radiomics signature was constructed with 4 features, but the AUC values were lower than that of the 3D signature. In the IDH-mutated subgroup, the 3D-radiomics signature presented AUCs of 0.950–1.000. Conclusions: The MRI-based radiomics signature can differentiate 1p/19q co-deletion status in LGG with or without predetermined IDH status. 3D-CE-T1-weighted radiomics features are more favorable than SC-CE-T1-weighted features in the establishment of radiomics signatures.

Background To explore the feasibility of diffusion-weighted imaging (DWI) metrics to predict the histologic subtypes and genetic status of gliomas (e.g., IDH, MGMT, and TERT) noninvasively. Methods One hundred and eleven patients with pathologically confirmed WHO grade II-IV gliomas were recruited retrospectively. Apparent diffusion coefficient (ADC) values were measured in solid parts of gliomas on co-registered T2-weighted images and were compared with each other in terms of WHO grading and genotypes using t-tests. Receiver operating characteristic analysis was performed to assess the diagnostic performances of ADC. Subsequently, multiple linear regression was used to find independent variables, which can directly affect ADC values. Results The values of overall mean ADC (omADC) and normalized ADC (nADC) of high grade gliomas and IDH wildtype gliomas were lower than low grade gliomas and IDH mutated gliomas (P Conclusion DWI metrics can predict glioma grading and IDH mutation noninvasively, but have limited use in detecting TERT mutation and MGMT methylation.

The objective of this study was to investigate the correlation between the amount of blood flow in the area of neovascularization within a carotid atherosclerotic plaque by superb microvascular imaging (SMI) and the microvessel density (MVD) determined by histopathological staining. Twenty-eight carotid atherosclerotic plaques were detected by SMI in 28 patients who underwent carotid endarterectomy. SMI was graded according to the visual methods as follows: grade I: no appearance of neovascularization within the plaque; grade II: punctate neovascularization; grade III: one or two linear neovascularizations within the plaque; and grade IV: multiple (> 2) linear neovascularizations throughout the plaque. The neovascularization density was determined by the CD31 complex staining method. There was a significant correlation between the density of neovascularization in histopathologic plaques and the blood flow grade found by SMI ( r = 0.788, p < 0.001). A significant difference was observed in SMI blood flow grade between the symptomatic and asymptomatic groups (χ2 = 2.634, p = 0.036). The MVD of plaques in the symptomatic group was significantly higher than that in the asymptomatic group ( t = 2.530, p = 0.018). The SMI-based classification was positively correlated with plaque thickness. SMI, which is a new nonultrasound contrast-enhanced imaging method, can effectively evaluate neovascularization in carotid atherosclerotic plaques and can be used as a novel method for the clinical prediction of stroke risk.

Extracorporeal cardiac shock wave therapy (CSWT) has been used to treat patients with severe coronary heart disease and cardiac failure with good results; however, the safety of this treatment is still controversial. Its safety in clinical setting and on microstructures has been confirmed, but the influence of shock wave on the ultrastructures of myocardial cells is not clear. In this study, 12 Sprague-Dawley rats were randomly divided into control (NC) and CSWT therapy (NC+SW) groups. The heart rate, blood pressure, serum troponin I (TNI), and cardiac ultrasound were evaluated, and the myocardial inflammatory responses and fibrosis changes were compared. The samples were observed by transmission electron microscopy to evaluate the changes in myocardial tissue ultrastructure. The CSWT had no significant influence on rat hemodynamics indices and serum TNI, did not affect left ventricular function, and did not cause myocardial inflammatory response and fibrosis changes. The scores of myocardial ultrastructure damage in the NC and NC+SW groups were 1.39 ± 0.982 and 2.42 ± 1.009, respectively ( P = .103). The CSWT did not cause significant additional damage to myocardial ultrastructures. The safety of CWST has been preliminarily proved at the clinical, microstructure, and ultrastructure levels, but its long-term safety needs further exploration.

Telomerase reverse transcriptase (TERT) promoter mutation status is an important biomarker for the precision diagnosis and prognosis prediction of lower grade glioma (LGG). This study aimed to construct a radiomic signature to noninvasively predict the TERT promoter status in LGGs. Eighty-three local patients with pathology-confirmed LGG were retrospectively included as a training cohort, and 33 patients from The Cancer Imaging Archive (TCIA) were used as for independent validation. Three types of regions of interest (ROIs), which covered the tumor, peri-tumoral area, and tumor plus peri-tumoral area, were delineated on three-dimensional contrast-enhanced T1 (3D-CE-T1)-weighted and T2-weighted images. One hundred seven shape, first-order, and texture radiomic features from each modality under each ROI were extracted and selected through least absolute shrinkage and selection operator. Radiomic signatures were constructed with multiple classifiers and evaluated using receiver operating characteristic (ROC) analysis. The tumors were also stratified according to IDH status. Three radiomic signatures, namely, tumoral radiomic signature, tumoral plus peri-tumoral radiomic signature, and fusion radiomic signature, were built, all of which exhibited good accuracy and balanced sensitivity and specificity. The tumoral signature displayed the best performance, with area under the ROC curves (AUC) of 0.948 (0.903–0.993) in the training cohort and 0.827 (0.667–0.988) in the validation cohort. In the IDH subgroups, the AUCs of the tumoral signature ranged from 0.750 to 0.940. The MRI-based radiomic signature is reliable for noninvasive evaluation of TERT promoter mutations in LGG regardless of the IDH status. The inclusion of peri-tumoral area did not significantly improve the performance.

Fully elucidating the molecular mechanisms of non-coding RNAs (ncRNAs), including micro RNAs (miRNAs) and long non-coding RNAs (lncRNAs), underlying hepatocarcinogenesis is challenging. We characterized the expression profiles of ncRNAs and constructed a regulatory mRNA-lncRNA-miRNA (MLMI) network based on transcriptome sequencing (RNA-seq) of hepatocellular carcinoma (HCC, n = 9) patients. Of the identified miRNAs (n = 203) and lncRNAs (n = 1,090), we found 16 significantly differentially expressed (DE) miRNAs and three DE lncRNAs. The DE RNAs were highly enriched in 21 functional pathways implicated in HCC (p in silico prediction and experimentally-validated evidence. We for the first time constructed a MLMI network of reciprocal interactions for 16 miRNAs, three lncRNAs, and 253 mRNAs in HCC. The predominant role of MEG3 in the MLMI network was validated by its overexpression in vitro that the expression levels of a proportion of MEG3-targeted miRNAs and mRNAs was changed significantly. Our results suggested that the comprehensive MLMI network synergistically modulated carcinogenesis, and the crosstalk of the network provides a new avenue to accurately describe the molecular mechanisms of hepatocarcinogenesis.

Liver hepatocellular carcinoma (LIHC) is the second leading cause of cancer mortality worldwide. Although cancer driver genes identified so far have been considered to be saturated or nearly saturated, challenges remain in discovering novel genes underlying carcinogenesis due to significant tumor heterogeneity. Here, in a small cohort of hepatitis B virus (HBV)-associated LIHC, we investigated the transcriptional patterns of tumor-mutated alleles using both whole-exome and RNA sequencing data. A graph clustering of the transcribed tumor-mutated alleles characterized overlapped functional clusters, and thus prioritized potentially novel oncogenes. We validated the function of the potentially novel oncogenes in vitro and in vivo. We showed that a component of the retromer complex—the vacuolar protein sorting-associated protein 35 (VPS35)—promoted the proliferation of hepatoma cell through the PI3K/AKT signaling pathway. In VPS35-knockout hepatoma cells, a significantly reduced distribution of membrane fibroblast growth factor receptor 3 (FGFR3) demonstrated the effects of VPS35 on sorting and trafficking of transmembrane receptor. This study provides insight into the roles of the retromer complex on carcinogenesis and has important implications for the development of personalized therapeutic strategies for LIHC.

Malignant triton tumor (MTT) is an extraordinarily uncommon and aggressive tumor which have poor prognosis. Malignant peripheral nerve sheath tumors with additional rhabdomyoblasts are found in MTT histologically. The prognosis of patients is poor. The goal of our study is to describe the largest number of cases characteristic and outcome, to our knowledge, such a presentation was not described in the English-language literature until now. From 1999 to 2014, 10 patients (5 women and 5 men) with a malignant triton tumor were treated at our institution. All these cases were followed-up and patient charts were analyzed for outcome. In our study, 3 cases of the Malignant triton tumors originate in the head, 2 cases in the joints, 2 cases in the retroperitoneum, 2 cases in the soft tissues of the thoracic wall, and 1 case in the prostate. Neoplasm associated with pain was the main manifestation. Patients have a poor prognosis. Completely surgical excision of the tumor is the only treatment. Additional radiation or chemotherapy show little effect. Malignant triton tumor is a rare sarcoma. The high probability of developing local recurrence and distant metastases could account for its poor prognosis.

Diffuse leptomeningeal glioneuronal tumour (DLGNT) is a rare disease classified in 2016. There are different views of the clinical, pathologic and neuroradiologic characteristics of DLGNT due to the minor studies on this disease. We describe a case of a 12-year-old boy who initially presented intermittent headache, vomiting and communicating hydrocephalus. A literature review is also presented summarizing the clinical characteristics and treatments of DLGNT. In our case, a ventriculoperitoneal shunt was applied to reduce intracranial pressure caused by communicating hydrocephalus. T1-weighted contrast-enhanced magnetic resonance imaging (MRI) showed linear enhancement, and microscopy showed tumour-like spindle cells. The diagnosis of DLGNT was confirmed, and temozolomide was administered. The clinical characteristics were similar in the reported cases, while the treatments showed differences. Ventriculoperitoneal shunts are effective for patients with hydrocephalus-related intracranial hypertension. Chemotherapy including temozolomide has shown varying outcomes, and further studies are expected.

Purpose The methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) promoter has been proven to be a prognostic and predictive biomarker for lower grade glioma (LGG). This study aims to build a radiomics model to preoperatively predict the MGMT promoter methylation status in LGG. Method 122 pathology-confirmed LGG patients were retrospectively reviewed, with 87 local patients as the training dataset, and 35 from The Cancer Imaging Archive as independent validation. A total of 1702 radiomics features were extracted from three-dimensional contrast-enhanced T1 (3D-CE-T1)-weighted and T2-weighted MRI images, including 14 shape, 18 first order, 75 texture, and 744 wavelet features respectively. The radiomics features were selected with the least absolute shrinkage and selection operator algorithm, and prediction models were constructed with multiple classifiers. Models were evaluated using receiver operating characteristic (ROC). Results Five radiomics prediction models, namely, 3D-CE-T1-weighted single radiomics model, T2-weighted single radiomics model, fusion radiomics model, linear combination radiomics model, and clinical integrated model, were built. The fusion radiomics model, which constructed from the concatenation of both series, displayed the best performance, with an accuracy of 0.849 and an area under the curve (AUC) of 0.970 (0.939-1.000) in the training dataset, and an accuracy of 0.886 and an AUC of 0.898 (0.786-1.000) in the validation dataset. Linear combination of single radiomics models and integration of clinical factors did not improve. Conclusions Conventional MRI radiomics models are reliable for predicting the MGMT promoter methylation status in LGG patients. The fusion of radiomics features from different series may increase the prediction performance.

Anti-protein kinase Cgamma (anti-PKCγ) antibodies are rare onconeural antibodies associated with paraneoplastic cerebellar degeneration (PCD). To date, only two patients with PCD and anti-PKCγ antibodies have been reported. Here, we report a Chinese patient with PCD and anti-PKCγ antibodies. Screening for tumor revealed lymphoepithelial carcinoma in tonsil. The patient's symptoms improved gradually after radiotherapy for the lymphoepithelial carcinoma and intravenous immunoglobulin immunotherapy.

// Qi Pan 1 , Xianli Long 1 , Liting Song 1 , Dachun Zhao 2 , Xiaoyuan Li 3 , Dewei Li 4 , Min Li 5 , Jinxue Zhou 6 , Xia Tang 1 , Hong Ren 1 , Keyue Ding 1 1 Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, P.R. China 2 Department of Pathology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, P.R. China 3 Department of Medical Oncology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, P.R. China 4 Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, P.R. China 5 Department of Hepatobiliary Surgery, Suining Central Hospital, Suining, Sichuan Province, P. R. China 6 Department of Hepatobiliary Surgery, Henan Tumor Hospital, Zhenzhou, Henan Province, P.R. China Correspondence to: Keyue Ding, email: ding.keyue@cqmu.edu.cn Keywords: hepatocellular carcinoma, transcriptome sequencing, weighted gene co-expression network, hub gene Received: February 26, 2016 Accepted: May 05, 2016 Published: May 23, 2016 ABSTRACT Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, and it remains a challenge to understand the genetic mechanisms underlying hepatocarcinogenesis. A global gene network of differential expression profiles in HCC has yet to be fully characterized. In the present study, we performed transcriptome sequencing (mRNA and lncRNA) in liver cancer and cirrhotic tissues of nine HCC patients. We identified differentially expressed genes (DEGs) and constructed a weighted gene co-expression network for the DEGs. In total, 755 DEGs (747 mRNA and eight lncRNA) were identified, and several co-expression modules were significantly associated with HCC clinical traits, including tumor location, tumor grade, and the α-fetoprotein (AFP) level. Of note, we identified 15 hub genes in the module associated with AFP level, and three ( SPX, AFP and ADGRE1 ) of four hub genes were validated in an independent HCC cohort ( n =78). Identification of hub genes for HCC clinical traits has implications for further understanding of the molecular genetic basis of HCC.

In previous studies, N,O-carboxymethyl chitosan has been shown to decrease the incidence and intensity of abdominal adhesions. In the present study, adhesions were induced in 220 rabbits using a double uterine horn model. Rabbits were randomized to receive an operation only or an operation+medical chitosan intraperitoneally. Twenty-two rabbits from each group were euthanized at one of five different times (Day 3, 7, 14, 28, or 42), and adhesion formation was given gross and histopathological scores. Reductions were observed in adhesion extent (P=0.0337) and tenacity (P=0.0271) as well as inflammation (P

To identify rare mutations and retrospectively estimate the cancer risk of a 45-year old female patient diagnosed with Li-Fraumeni syndrome (LFS), who developed nine primary malignant neoplasms in a period of 38 years, we conducted next-generation sequencing in this patient. Whole-genome and whole-exome sequencing were performed in DNA of whole blood obtained a year prior to the diagnosis of acute myeloid leukemia (AML) and at the time of diagnosis of AML, respectively. We analyzed rare mutations in cancer susceptibility genes using a candidate strategy and estimated cancer risk using the Risk-O-Gram algorithm. We found rare mutations in cancer susceptibility genes associated with an increased hereditary cancer risk in the patient. Notably, the number of mutated genes in p53 signaling pathway was significantly higher than expected (p=0.02). However, the phenotype of multiple malignant neoplasms of the studied patient was unlikely to be caused by accumulation of common cancer risk alleles. In conclusion, we established the mutation profile in a rare case of Li-Fraumeni syndrome, illustrating that the rare mutations rather than the cumulative of common risk alleles leading to an increased cancer risk in the patient.

There is a discordance in the immunohistochemical markers between primary breast cancer and recurrent or metastatic breast cancer. This study aimed to assess the recent trends and prognostic features in the treatment of recurrent or metastatic breast cancerOverall, 107 patients were identified from January 2001 to August 2018 at the Peking Union Medical College Hospital, Beijing, and People's Republic of China to obtain a cohort of breast carcinoma patients who were confirmed to have recurrent or metastatic breast cancer by histopathology. We evaluated patient and tumor characteristics and examined the relationships between these factors and prognosis.The estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2) positivity, and Ki67 index in primary breast cancer were 63.6% (68/107), 58.9% (63/107), 19.8% (21/106) and 75.8% (75/99), respectively, while those in recurrent or metastatic lesions were 60.6% (65/107) (P = .672), 46.7% (50/107) (P = 0.013), 23.8% (25/105) (P = 0.482)and 83.5%(81/97)(P = 0.178), respectively. The discordance rate of HER2 expression was 10.6% (11/104), while that of PR expression was 23.3% (21/90). HER2 was the most stable biomarker. The discordance rates for luminal A and HER2 were as high as 100% and 25%, respectively, while the luminal B and triple negative values were as low as 8.3% and 5.3%, respectively.ER and PR positivity and the Ki-67 index tended to increase due to recurrence or metastases; however, the discordance for PR and Ki-67 was high. PR is more variable than ER in the expression of primary and recurrent or metastatic breast cancer. The expression of HER2 receptor was the most stable and the discordance rate of triple negative breast cancer was the lowest. Therefore, although changes in biomarkers are due to recurrence or metastasis, pathological confirmation and exploration of markers are very important.

Background aims The purpose of the study was to investigate the feasibility of in vitro and in vivo bioluminescence imaging (BLI), fluorescence imaging (FI) and magnetic resonance imaging (MRI) to trace transplanted bone mesenchymal stromal cells (BMSCs) labeled with the firefly luciferase (Fluc) reporter gene, CyI dyes and ultra-small super-paramagnetic iron oxide (USPIO) particles. Methods Fluc-transfected BMSCs were further labeled with CyI dyes and USPIO particles, respectively. Acute myocardial infarction models of different weighted Sprague-Dawley rats and Balb/c mice were established, and BLI and FI were performed in vivo and ex vivo to determine the optimal method of optical imaging. Finally, BLI and MRI were selected to trace transplanted BMSCs in a murine model in vivo . Results BLI was found to be the optimal optical imaging method in vivo , compared with FI, and mice were found to be the optimal animal model, compared with rats. A significant BLI signal intensity was detected in the heart region in the BMSC-treated mice group (40,552 ± 6073 counts, n = 26) and gradually decreased below the detection threshold. Two distinct hypo-intense regions were observed in the anterior wall of the heart, where stem cells were injected on MR images obtained with the gradient recalled echo cine sequence in the BMSC-treated mice group. Conclusions Transplanted BMSCs labeled with Fluc reporter gene and USPIO particles can be traced with the use of BLI and MRI in a mouse model of acute myocardial infarction.

To explore the effect of microRNA-26b (miR-26b) in non-small cell lung cancer (NSCLC) cells, we investigated the mRNA levels of miR-26b in 4 NSCLC cell lines and 10 clinical samples from human patients with NSCLC by quantitative reverse transcriptase polymerase chain reaction. It was found that miR-26b was significantly down-regulated in both NSCLC cells and human carcinoma tissues. Synthetic oligonucleotides were used to up-regulate or down-regulate miR-26b in NSCLC cell lines H1299 and A549 cells. Results showed that both down-regulating and up-regulating miR-26b had no effect on cancer cell proliferation in H1299 or A549 cells, whereas miR-26b over-expression increased cancer cell migration and reduced cisplatin chemosensitivity. Phosphatase and tensin homolog (PTEN) was confirmed to be directly bound by miR-26b by dual-luciferase reporter assay, and was down-regulated in miR-26b over-expressing NSCLC cells. Finally, when PTEN was up-regulated in NSCLC cells, it reversed the effects of miR-2b over-expression on NSCLC migration and cisplatin chemosensitivity. In conclusion, our data showed a functional mechanism of miR-26b in regulating NSCLC. It indicates that miR-26b may regulate NSCLC migration and chemosensitivity through the regulation of PTEN.

Multiple rectal carcinoids are rare. Due to the unreliability of endoscopic polypectomy in treating these submucosal lesions, a laparotomy is usually performed. We present a case report on multiple rectal carcinoids with three carcinoid foci < 10 mm in diameter located in the mid-rectum. Preoperative examination showed the lesions to be confined to the submucosal layer with no perirectal nodal involvement. A transanal endoscopic microsurgery was successfully performed to remove the three lesions with accurate full-thickness resection followed by secured suture closure. The postoperative pathology revealed neuroendocrine tumors G1 (carcinoids) located within the submucosal layer without lymphatic or vessel infiltration. Both the deep and lateral surgical margins were completely free of tumor cells. The patient recovered quickly and uneventfully. No tumor recurrence was observed at the six-month follow-up. For the multiple small rectal carcinoids without muscularis propria or lymphatic invasion, transanal endoscopic microsurgery offers a reliable and efficient alternative approach to traditional laparotomy for select patients, with the added advantages of minimally invasive surgery.

ObjectiveThe aim of the study was to investigate the clinical manifestations, diagnosis, treatment, and prognosis of primitive neuroectodermal tumors (PNETs) in the female genital tract.MethodsFrom April 2001 to May 2013, the clinicopathologic characteristics, treatments, outcomes, and prognosis of 11 patients with PNET in the female genital tract were analyzed retrospectively at our hospital.ResultsThe location of PNET in the 11 patients presented here included vulva (2 patients), cervix (2 patients), uterus and its ligament (5 patients), and the ovaries (2 patients). Ages ranged from 18 to 59 years (median, 31 years).The main clinical manifestations of PNET in the female genital tract are irregular vaginal bleeding (6 patients), pelvic mass, uterine enlargement, and rapidly increasing vulvar mass (8 patients), and vulvar pain and lower abdominal pain (5 patients). The CA125 levels of 8 patients were elevated before the operations and reduced to normal when the diseases were controlled, while the levels increased as the tumor was progressive. Results for the most commonly used immunohistochemistry studies revealed CD99 in 11 of the 11 tumors, synaptophysin in 6 of the 7 positive tumors, and neuron-specific enolase in 6 of the 6 tumors. Ten patients underwent surgical resection. Nine of them underwent preoperative or/and postoperative combination chemotherapy. The follow-up of 10 patients were available and ranged from 1 to 145 months (median, 30.5 months), 3 of whom experiencing recurrence.ConclusionsPrimitive neuroectodermal tumor is very rare and can originate from any part of the female genital tract. The tumors had different manifestations but the same pathologic features. CA125 may be an important marker for prognosis and follow-up of PNET of the female internal genital tract.

The differential diagnosis of primary central nervous system lymphoma from glioblastoma multiforme (GBM) is essential due to the difference in treatment strategies. This study retrospectively reviewed 77 patients (24 with lymphoma and 53 with GBM) to identify the stable and distinguishable characteristics of lymphoma and GBM in 18F-fluorodeocxyglucose (FDG) positron emission tomography (PET) images using a radiomics approach. Three groups of maps, namely, a standardized uptake value (SUV) map, an SUV map calibrated with the normal contralateral cortex (ncc) activity (SUV/ncc map), and an SUV map calibrated with the normal brain mean (nbm) activity (SUV/nbm map), were generated, and a total of 107 radiomics features were extracted from each SUV map. The margins of the ROI were adjusted to assess the stability of the features, and the area under the curve (AUC) of the receiver operating characteristic curve of each feature was compared with the SUVmax to evaluate the distinguishability of the features. Nighty-five radiomics features from the SUV map were significantly different between lymphoma and GBM, 46 features were numeric stable after marginal adjustment, and 31 features displayed better performance than SUVmax. Features extracted from the SUV map demonstrated higher AUCs than features from the further calibrated maps. Tumors with solid metabolic patterns were also separately evaluated and revealed similar results. Thirteen radiomics features that were stable and distinguishable than SUVmax in every circumstance were selected to distinguish lymphoma from glioblastoma, and they suggested that lymphoma has a higher SUV in most interval segments and is more mathematically heterogeneous than GBM. This study suggested that 18F-FDG-PET-based radiomics is a reliable noninvasive method to distinguish lymphoma and GBM., Highlights • 18F-FDG-PET is a reliable technique to differentiate primary CNS lymphoma from GBM. • Radiomics identify the stable and distinguishable characteristics of lymphoma and GBM. • 18F-FDG-PET-based radiomics provide assistance to the preoperative diagnosis.

Aims To determine clinicopathological criteria and molecular markers helpful in distinguishing adrenocortical carcinomas (ACCs) from adrenocortical adenomas (ACAs). Methods and results We analysed retrospectively the clinical and pathological features of 50 adrenal cortical tumours, and tested the expression of miR483-3p by in-situ hybridization as well as the expression of IGF2 and Smad4 by immunohistochemistry. We found that tumour size, tumour weight, hormonal function and the Weiss system are all high-efficacy criteria for differentiating malignant from benign tumours (P

Objective To analyze the recurrence features and prognostic factors of patients with intravenous leiomyomatosis after complete tumor resection. Methods We conducted a retrospective study of 58 patients with intravenous leiomyomatosis with follow-up data out of 75 patients treated from September 2005 to September 2015 and an analysis of postoperative recurrence features and prognostic factors. Results The average patient age was 45.4 years. The preoperative diagnosis rate was low. Among the 58 total patients, 31 had tumors that spread to the inferior vena cava and heart. During the median follow-up of 11.5 months, recurrence occurred in 18 patients at a rate of 31.0% (95% confidence interval 19.0-43.0%). Recurrence was associated with the preoperative tumor extent, and large vein involvement (16/31 compared with 2/27, P=.02) was a risk factor for postoperative recurrence. Postoperative recurrence was not associated with age (1/10 in 50 years or older compared with 17/48 younger than 50 years, P=.35), involvement of the heart (10/22 compared with 8/36, P=.28), resection of the uterus (16/51 compared with 2/7, P=.84) or bilateral ovaries (15/40 compared with 3/18, P=.65) with complete tumor removal, the choice of one-stage or two-stage surgery (11/45 for one-stage surgery compared with 7/13 for two-stage surgery, P=.20), postoperative antiestrogen hormone therapy (10/24 compared with 8/34, P=.53), or the hormone therapy duration (5/17 in the over-6-months group compared with 13/41 in the under-6-months group, P=.81). Conclusion The postoperative recurrence rate of intravenous leiomyomatosis was high, and large vein involvement was associated with an increased risk of recurrence. Continued postoperative follow-up is important. Neither resection of bilateral ovaries nor postoperative hormone therapy was associated with recurrence.

Background Isolated hypothalamic-pituitary Langerhans cell histiocytosis (HPLCH) is very rare. We investigated the clinicopathological characteristics, endocrine function changes, BRAFV600E mutations and treatments of isolated HPLCH. Methods We identified seven patients with isolated HPLCH by reviewing the clinical and pathological files in our hospital from 2007 to 2015. The clinical characteristics of the seven patients were retrospectively reviewed, especially the endocrine function changes. Immunostaining and mutation profiling of BRAFV600E were performed. Results The seven HPLCH patients included three men and four women, aged 9–47 years. All patients presented with symptoms of central diabetes insipidus (CDI), and four displayed anterior pituitary hypofunction as well. Magnetic resonance imaging showed hypothalamic-pituitary axis involvement in all patients. There was no evidence for the involvement of other organs in all seven patients. Langerhans cell histiocytosis was confirmed by neuroendoscopic procedures, and immunohistochemical staining showed that all cases (7/7) were positive for CD68, CD1a, Langerin, and S-100. The BRAFV600E mutation was detected in three of the six cases (3/6). Six patients had follow-up information; all received desmopressin acetate and high-dose corticosteroid therapy, and two patients received radiotherapy. Conclusions Our study indicated that all patients with isolated HPLCH had CDI as the earliest symptom, and more than half of the patients had anterior pituitary deficiencies. The BRAFV600E mutation is a common genetic change in HPLCH patients. Treatment of HPLCH patients is difficult, and the progressive loss of endocrine function is irreversible in most cases.

Objective The electrocardiography (ECG) was the simplest and common adjunctive diagnostic tool for cardiac amyloidosis (CA). We sought to clarify the findings of ECG in patients with CA in order to early identification of CA according to the findings of ECG. Methods A total of 276 patients with diagnosis of systemic amyloidosis admitted to Peking Union Medical College Hospital from January 2000 to December 2011, were enrolled. Two groups were classified according to the cardiac involvement or not, namely CA (n = 189) and control (n = 87) groups. The low voltage on limb leads defined by the amplitude of the QRS complex in each limb leads ≤0.5 mV. The pseudo-infarct pattern defined by the presence of pathologic Q waves on at least two contiguous leads on ECG without obstructive coronary artery disease. Results The mean age was 55 ± 12 (15–88) years, 168 patients (61%) were male. Atrial arrhythmia (15.9% vs 3.4%, P = 0.003), low voltage on limb leads (54.5% vs 20.7%, P

The expression of mutant forms of proteins (e.g., oncogenes and tumor suppressors) has implications in cancer biology and clinical practice. Initial efforts have been made to characterize the transcription of tumor-mutated alleles; however, few studies have been reported to link tumor-mutated alleles to proteomics. We aimed to characterize the transcriptional and translational patterns of tumor-mutated alleles. We performed whole-exome sequencing, RNA-seq and proteome profiling in a hyper-mutated patient of hepatocellular carcinoma. Using the patient as a model, we show that only a small proportion of tumor-mutated alleles were expressed. In this case, 42% and 3.5% of the tumor-mutated alleles were identified to be transcribed and translated, respectively. Compared with genes with germline variations or without mutations, somatic mutations significantly reduced protein expression abundance. Using the transcriptional and translational patterns of tumor-mutated alleles, we classified the mutations into four types and only one type may be associated with the liver cancer and lead to hepatocarcinogenesis in the patient. Our results demonstrate how tumor-mutated alleles are transcribed and translated and how the expression enables the classification of somatic mutations that cause cancer. Leveraging multiple ‘omics’ datasets provides a new avenue for understanding patient-specific mutations that underlie carcinogenesis.

Introduction: Complete non-mosaic trisomy 22 is a fatal chromosomal disorder that only few fetuses can survive over 12 weeks as reported. Prenatal sonographic findings combined with postnatal or postmortem discoveries showed characteristic multi-systematic anomalies. Patient concerns: The unborn baby of a 35-year-old pregnant woman was found to have several anomalies during a prenatal sonographic scan, including intrauterine growth retardation, ventricular septal defect, flat facial profile, and unclear bilateral kidney structures. Diagnoses: The fetus was diagnosed as having complete non-mosaic trisomy 22 by chromosomal analysis. Interventions: The pregnancy was terminated at 24 weeks, and autopsy was permitted. Outcomes: Postmortem examinations revealed additional long-sectional spina bifida occulta and imperforate anus. Conclusions: This was the first time a case of spinal cord defect was reported in trisomy 22 fetuses. More attention should be paid to the spinal cord during sonographic examinations in trisomy 22 fetuses.