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ABSTRACT Objective: To explore the diagnostic value of the TUIAS (SW_TH01/II) computer-aided diagnosis (CAD) software system for the ultrasound Thyroid Imaging Reporting and Data System (TI-RADS) features in thyroid nodules. Materials and methods: This retrospective study enrolled patients with thyroid nodules in Shanghai East Hospital between January 2017 and October 2021. The novel CAD software (SW_TH01/II) and three sonographers performed a qualitative analysis of the ultrasound TI-RADS features in aspect ratio, margin irregularity, margin smoothness, calcification, and echogenicity of the thyroid nodules. Results: A total of 225 patients were enrolled. The accuracy, sensitivity, and specificity of the CAD software in “aspect ratio” were 95.6%, 96.2%, and 95.4%, in “margin irregularity” were 90.7%, 90.5%, and 90.9%, in “margin smoothness” were 85.8%, 88.5%, and 83.0%, in “calcification” were 83.6%, 81.7%, and 82.0%, in “homogeneity” were 88.9%, 90.6%, and 82.2%, in “major echo” were 85.3%, 88.0%, and 85.4%, and in “contains very hypoechoic echo” were 92.0%, 90.0%, and 92.4%. The analysis time of the CAD software was significantly shorter than for the sonographers (2.7 ± 1.6 vs. 29.7 ± 12.7 s, P < 0.001). Conclusion: The CAD system achieved high accuracy in describing thyroid nodule features. It might assist in clinical thyroid nodule analysis.

BackgroundsApproximately 75% of bladder cancer occurrences are of the non-muscle-invasive type. The estimated five-year survival rate is 26%–55%. Currently, there is no reliable biomarker available for early diagnosis and prognosis of bladder cancer. The present study aims to identify a biomarker using bioinformatic approaches to provide a new insight in clinical research for early diagnosis and prognosis of bladder cancer.MethodsClinical data and a transcriptome of bladder cancer were obtained from TCGA, GEO, GETx, and UCSC Xena. The differential expressed gene (DEG) analysis, weighted gene co-expression network analysis (WGCNA), and survival analysis using the Kaplan-Meier and Cox proportional-hazards models were used to identify the Microtubule-associated Proteins 1A (MAP1A). on overall survival (OS) and disease-free survival (DFS) was analyzed using GEPIA and GETx databases. The TIMER 2.0 database predicted the correlation between MAP1A and immunocytes and immune checkpoints. Target prediction of the regulated competing endogenous RNAs (ceRNAs) network of MAP1A was performed using starBase and TargetScan. Cystoscope v3.7.2 software was used to visualize the ceRNA coexpression network. The R programming language v4.0.2 was applied as an analytic tool. Gene expression of MAP1A verified by RT-qPCR.ResultsThe low expression of MAP1A was verified in bladder cancer tissues and bladder cancer cell lines SW780 and 5637. P < 0.001 were obtained by Kaplan-Meier survival analysis and Cox proportional hazards model, with a hazard ratio (HR) of 1.4. Significant correlations between MAP1A and OS (P < 0.001, HR = 1.9) as well as DFS (P < 0.05, HR = 1.7) in bladder cancer were identified through gene expression profiling interactive analysis (GEPIA), indicating MAP1A may be a high-risk factor. Significant correlation in single copy-number variation of MAP1A gene with CD8+ T cells, and myeloid dendritic cells (MDCs) (P < 0.05) was noted. MAP1A expression was shown to be significantly correlated with the amount of CD4+ T cells and CD8+ T cells, MDCs, macrophages, and neutrophils in a statistically significant positive manner (P < 0.001). However, the MAP1A expression demonstrated a strong negative connection with B cells (P < 0.001). Except for macrophage M1 genes IRF5 and PTGS2, MAP1A expression was significantly correlated with the gene levels in immunocytes such as CD4+ T cells, CD8+ T cells, B cells, dendritic cells (DCs), macrophages, and neutrophils (Cor > 0.2, P < 0.001), as well as immune checkpoint related genes including cytotoxic t-lymphocyte-associated protein 4 (CTLA-4), programmed death 1 (PD-1), programmed death ligand 1 (PD-L1) (P < 0.001). Finally, we predicted that the MAP1A-interacting miRNA was miR-34a-5p, and the MAP1A endogenous competing RNAs were LNC00667, circ_MAP1B, and circ_MYLK, respectively. These findings support the need for further studies on the mechanism underlying the pathogenesis of this disease.ConclusionMAP1A is considered as a prospective biomarker for early diagnosis, therapeutic observation, and prognosis analysis in bladder cancer.

Abstract Recent studies have revealed the significant dysregulation of m6A level in peripheral blood in several cancer types and its value in diagnosis. Nonetheless, a biomarker for accurate screening of multiple cancer types has not been established based on the perspective of m6A modification. In this study, we aimed to develop a serum diagnostic signature based on the m6A target miRNAs for the mass detection of cancer. A total of 14965 serum samples with 12 cancer types were included. Based on training cohort (n=7299), we developed the m6A-miRNAs signature using a support vector machine algorithm for cancer detection. The m6A-miRNAs signature showed high accuracy, and its area under the curve (AUC) in the training, internal validation and external validation cohort reached 0.979 (95%CI 0.976 - 0.982), 0.976 (95%CI 0.973 - 0.979) and 0.936 (95%CI 0.922 - 0.951), respectively. In the performance of distinguishing cancer types, the m6A-miRNAs signature showed superior sensitivity in each cancer type and presented a satisfactory AUC in identifying lung cancer, gastric cancer and hepatocellular carcinoma. Additionally, the diagnostic performance of m6A-miRNAs was not interfered by the gender, age and benign disease. In short, this study revealed the value of serum circulating m6A miRNAs in cancer detection and provided a new direction and strategy for the development of novel biomarkers with high accuracy, low cost and less invasiveness for mass cancer screening, such as RNA modification.

Primary hepatopancreatobiliary lymphoma (PHPBL) is extremely rare, which is defined as a lympho-proliferative disease confined to the hepatobiliary system and pancreas without any involvement of lymph nodes, bone marrow, or other organs. The clinical and imaging manifestations of PHPBL are variable and non-special, which are akin to those of tumors of the hepatobiliary and pancreatic systems. The overall prognosis and management of PHPBL differ from those of other tumors in the hepatobiliary system and pancreas. Proper diagnosis and prompt treatment are essential for improving clinical outcomes. Due to its rarity, the optimal treatment has not been issued. However, combination chemotherapy is considered as a standard treatment for them. This review provides an overview of the pathogenesis, diagnosis, pathology, and management of PHPBL and offers clinicians the diagnosis and management schedule for PHPBL.

Abstract Objective Glycosylated hemoglobin (HbA1c) has obvious clinical value in the diagnosis of diabetes, but the conclusions on the diagnostic value of diabetic retinopathy (DR) are not consistent. This study aims to comprehensively evaluate the accuracy of glycosylated hemoglobin in the diagnosis of diabetic retinopathy through the meta-analysis of diagnostic tests. Methods Cochrane Library, Embase, PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), China Wanfang Database, Chinese Biomedical Literature Database (CBM) were searched until November, 2020. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool was used to assess the quality of the included studies. The pooled sensitivity, specificity, positive likelihood ratio (+LR), negative likelihood ratio (-LR), diagnostic odds ratio (DOR) and areas under the receiver operating characteristic (ROC) curve were calculated by Stata 15.0 software. Results After screening, 18 high-quality papers were included. The results of meta-analysis showed that the combined DOR = 18.19 (95% CI: 10.99–30.11), the sensitivity= 0.81 (95% CI): 0.75 ~ 0.87), specificity = 0.81 (95%CI: 0.72 ~ 0.87), +LR = 4.2 (95%CI: 2.95 ~ 6.00), −LR = 0.23 (95%CI: 0.17 ~ 0.31), and the area under the Summary ROC curve was 0.88 (95%CI: 0.85 ~ 0.90). Conclusion The overall accuracy of HbA1cC forin diagnosing diabetic retinopathy is good. As it is more stable than blood sugar and is not affected by meals, it may be a suitable indicator for diabetic retinopathy.

PurposeTumor-educated platelets (TEPs) are a promising liquid biopsy in many cancers. However, their role in renal cell carcinoma (RCC) is unknown. Thus, this study explored the diagnostic value of TEPs in RCC patients.MethodsPlatelets were prospectively collected from 24 RCC patients and 25 controls. RNA-seq was performed to identify the differentially expressed genes (DEGs) between RCC patients and controls. Besides, RNA-seq data of pan-cancer TEPs were downloaded and randomly divided into training and validation sets. A pan-cancer TEP model was developed in the training set using the support vector machine (SVM) and validated in the validation set and our RCC dataset. Finally, an RCC-based TEP model was developed and optimized through the SVM algorithms and recursive feature elimination (RFE) method.ResultTwo hundred three DEGs, 64 (31.5%) upregulated and 139 (68.5%) downregulated, were detected in the platelets of RCC patients compared with controls. The pan-cancer TEP model had a high accuracy in detecting cancer in the internal validation (training set, accuracy 98.8%, AUC: 0.999; validation set, accuracy 95.4%, AUC: 0.972; different tumor subtypes, accuracy 86.6%–96.1%, AUC: 0.952–1.000). However, the pan-cancer TEP model in the external validation had a scarce diagnostic value in RCC patients (accuracy 48.7%, AUC: 0.615). Therefore, to develop the RCC-based TEP model, the gene biomarkers mostly contributing to the model were selected using the RFE method. The RCC-based TEP model containing 68 gene biomarkers reached a diagnostic accuracy of 100% (AUC: 1.000) in the training set, 88.9% (AUC: 0.963) in the validation set, and 95.9% (AUC: 0.988) in the overall cohort.ConclusionTEPs could function as a minimally invasive blood biomarker in the detection of RCC.

Abstract Background The expression of Kelch-like protein 18 (KLHL18) in non-small cell lung cancer (NSCLC) is lower than that in normal lung tissue according to the Gene Expression Profiling Interactive Analysis database. KLHL18 is a BTB domain protein and binds cullin 3 (CUL3). However, whether this complex participates in ubiquitination-mediated protein degradation in NSCLC is unclear. Therefore, we aimed to investigate the role of KLHL18 in human NSCLC cells. Results We found that KLHL18 is downregulated in cancer cells and is associated with poor prognosis. Further, its expression was significantly associated with tumor node metastasis (TNM) stage, lymph node metastasis, and tumor size. In vitro analysis of NSCLC cells showed that overexpressing KLHL18 inhibited cell proliferation, migration, and invasion. We found that the tumor-inhibitory effect of the KLHL18 protein was achieved by promoting the ubiquitination and degradation of phosphatidylinositol 3-kinase (PI3K) p85α and inhibiting the expression of PD-L1 protein, ultimately preventing tumor cell immune escape. Conclusions Our results identified the tumor-suppressive mechanism of KLHL18 and suggested that it is closely related to NSCLC occurrence and development. Further investigation of the underlying mechanism may provide new targets for NSCLC treatment.

Background: The head-up tilt test (HUTT) is a useful diagnostic tool in patients with suspected vasovagal syncope (VVS).Objectives: We aimed to investigate the direct drug-potentiated HUTT in patients with recurrent syncope or precursor syncope and to assess the diagnostic value of the direct drug-potentiated HUTT.Methods: The medical history and direct drug-potentiated HUTT records of patients who complained of syncope or precursor syncope and who visited The Xianyang Central Hospital from January 2016 to December 2020 were retrospectively reviewed.Results: A total of 4,873 patients (age = 43.8 ± 17.6 years; male = 2,064 [42.4%]) were enrolled in our study. Overall, 2,343 (48.1%) showed positive responses as follows: 1,260 (25.9%) with the mixed type, 34 (0.7%) with the cardioinhibitory type, 580 (11.9%) with the vasodepressor type, 179 (3.7%) with postural tachycardia syndrome (POTS), and 290 (6.0%) with orthostatic hypotension (OH). The study showed that prior to syncope or near-syncope symptoms, patients first presented an increase in heart rate (HR), followed by decreases in blood pressure (BP) and HR successively. Among the patients in the syncope group, the sensitivity of the HUTT was 65.9%, which was significantly higher than a sensitivity of 44.8% for patients in the non-syncope group (P < 0.01). The sensitivity of the HUTT was higher for females than males in both the syncope group (52.6% in males and 77.9% in females, P < 0.01) and the non-syncope group (36.5% in males and 50.6% in females, P < 0.01). Within the four age groups (60 years old), the sensitivities were 74.7%, 67.7%, 45.6%, and 31.2%, respectively. And all gender, age and symptom (whether suffered from a syncope or not) significantly affected the positive responses of HUTT. There were two adverse events and no deaths during the HUTT in this study.Conclusion: The direct drug-potentiated HUTT is a safe and highly sensitive tool with which to diagnose VVS. Patients with precursor syncope symptoms without syncope should undergo a HUTT, especially young females presenting with weakness and sweating, which can decrease the probability of a misdiagnosis or a missed diagnosis.

Background: The clinical behavior and management of poorly differentiated thyroid carcinoma (PDTC) are very different from papillary thyroid carcinoma (PTC). By comparing the clinical and ultrasonographic features between the two tumors, we proposed to provide more possibilities for recognizing PDTC before treatment. Methods: The data of 13 PDTCs and 39 age- and gender-matched PTCs in Peking Union Medical College Hospital between December 2003 and September 2013 were retrospectively reviewed. The clinical and ultrasonic features between the two groups were compared. Results: The frequencies of family history of carcinoma, complication with other thyroid lesions, lymph node metastases, recurrent laryngeal nerve injuries, and distant metastases were higher in PDTCs (30.8%, 61.6%, 69.2%, 23.1%, and 46.2%, respectively) than those in PTCs (2.6%, 23.1%, 25.6%, 2.6%, and 2.6%, respectively) (P < 0.05). The mortality rate of PDTCs was greatly higher than PTCs (P < 0.01). Conventional ultrasound showed that the size of PDTCs was larger than that of PTCs (3.1 ± 1.9 cm vs. 1.7 ± 1.0 cm). Clear margins and rich and/or irregular blood flow were found in 92.3% of PDTCs, which differed substantially from PTCs (51.7% and 53.8%, respectively) (P < 0.05). Conclusions: PDTC is more aggressive and its mortality rate is higher than PTCs. Accordingly, more attention should be given to suspicious thyroid cancer nodules that show large size, regular shape, and rich blood flow signals on ultrasound to exclude the possibility of PDTCs.

Background: Some ultrasonographic (US) signs overlap between benign and malignant nodules. The purpose of this study was to raise a special US sign of benign thyroid nodules, termed the “onion skin-liked sign.” Methods: Twenty-seven patients with 27 nodules who shrank naturally and the “onion skin-liked sign” appeared on the final US images were enrolled in the study. The ultrasound characters and risk stratifications at the start and end of observation were compared. Then, thirty goiters with fibrosis and thirty papillary thyroid carcinomas (PTC) were randomly selected from the database of our hospital, matched the sizes of 27 nodules at the end point of observation. The differences of “onion skin-liked sign” between the two groups were analyzed. Results: The average duration of follow-up of 27 nodules was 24.0 ± 12.2 months (range, 12–65 months). At the end of the follow-up, the size of the nodules decreased on average by 1.26 ± 0.82 cm (range, 0.3–3.4 cm) and calcification was found in 21 nodules, compared with only 2 nodules with calcification at the start of the follow-up. In addition, only negligible or no blood flow signal could be detected at the periphery of all the nodules and 100% (27/27) were high suspicion at the end of observation. In matched groups, all PTC showed high suspicion of malignancy, 18/30 (60%) goiters with fibrosis were high suspicion and 11/30 (37%) were intermediate suspicion. Twenty-two patients in the group of nodular fibrosis presented “onion skin-liked sign,” which was not shown in any patient of PTC group. The sensitivity, specificity, positive predictive value, and negative predictive value of “onion skin-liked sign” in predicting nodular goiter with fibrosis were 73.3%, 100%, 100%, and 78.9%, respectively. Conclusions: The “onion skin-liked sign” was a characteristic US feature of benign thyroid nodules detected in the follow-up of thyroid nodules. It is useful to differentiate PTCs and nodular goiters with fibrosis.

Background: Age-induced sarcopenia negatively affects walking stability and increases the risk of falls, which is the leading cause of accidental death in the elderly. Objective: This study aimed to analyze and contrast body composition and gait characteristics in those with sarcopenia in relation to healthy controls to shed some light on the prevention of falls in elderly patients with sarcopenia. Materials and Methods: In this study, 68 community dwellers were scanned by the Hologic QDR-4500A Dual-energy X-ray absorptiometry (DXA). The appendicular lean mass index (ALMI) results were used to distinguish the normal participants from those with sarcopenia: 24 in the sarcopenia group, and 44 into the normal group. The participants were asked to undergo gait analysis on a plantar pressure measurement system. Statistical analysis was conducted to contrast both groups' gait and butterfly parameters from their gait test, and then a gait forward dynamics method was performed to quantify the analysis for both groups. Results: The ALMI of the female was not related to their age (r = 0.06) while that of the male was weakly related (r = 0.17). Body mass index (BMI) from both groups was normal, although with a statistically greater BMI from the normal group compared with sarcopenia (p < 0.001). Greater values and significant differences were found in step length and stride length from the normal elderly group (p < 0.01), and so was the length of the gait line and single support line (p < 0.05). Gait forward dynamics analysis results showed no motor neural or musculoskeletal disorders in their gait performance from the sarcopenia group. Conclusion: For the elderly, age did not largely affect the ALMI, BMI, or T-score, but BMI and ALMI were strongly correlated. In this study, significant differences were found in certain gait parameters between the elderly with sarcopenia and the normal elderly, which were related to absolute muscle strength, suggesting that sarcopenia was a disease mainly caused by decreased muscle mass. In addition, when abnormities were identified in step length, stride length, length of gait line, or length of single support line, it is proposed to take a DXA scan to confirm whether the elderly suffer from sarcopenia. [ABSTRACT FROM AUTHOR]

Objective: We used U-shaped convolutional neural network (U_Net) multi-constraint image segmentation method to compare the diagnosis and imaging characteristics of tuberculosis and tuberculosis with lung cancer patients with Computed Tomography (CT). Methods: We selected 160 patients with tuberculosis from the severity scoring (SVR) task is provided by Image CLEF Tuberculosis 2019. According to the type of diagnosed disease, they were divided into tuberculosis combined with lung cancer group and others group, all patients were given chest CT scan, and the clinical manifestations, CT characteristics, and initial suspected diagnosis and missed diagnosis of different tumor diameters were observed and compared between the two groups. Results: There were more patients with hemoptysis and hoarseness in pulmonary tuberculosis combined with lung cancer group than in the pulmonary others group (P<0.05), and the other symptoms were not significantly different (P>0.05). Tuberculosis combined with lung cancer group had fewer signs of calcification, streak shadow, speckle shadow, and cavitation than others group; however, tuberculosis combined with lung cancer group had more patients with mass shadow, lobular sign, spines sign, burr sign and vacuole sign than others group. Conclusion: The symptoms of hemoptysis and hoarseness in pulmonary tuberculosis patients need to consider whether the disease has progressed and the possibility of lung cancer lesions. CT imaging of pulmonary tuberculosis patients with lung cancer usually shows mass shadows, lobular signs, spines signs, burr signs, and vacuoles signs. It can be used as the basis for its diagnosis. Simultaneously, the U-Net-based segmentation method can effectively segment the lung parenchymal region, and the algorithm is better than traditional algorithms. [ABSTRACT FROM AUTHOR]

Background: Fluorouracil implants are widely used in peritoneal interstitial chemotherapy. Curative effects have been obtained, but implants have also caused some complications. Case presentation: We performed an analysis of a 66-year-old male patient's case history, as well as conventional pathological analysis and Raman spectroscopic detection of the diaphragmatic tumor. We also analyzed the underlying causes of this condition to prevent complications and reduce misdiagnoses in future cases. The patient had a history of peritoneal fluorouracil implantation. Pathological analysis of the diaphragmatic mass revealed foreign particles, and Raman detection showed that the mass contained fluorouracil. Conclusion: Fluorouracil implants may persist due to the high concentrations of this drug used in peritoneal chemotherapy. This finding should provide guidance and improve the application of peritoneal implants. In clinical trials, and the diagnosis of liver metastasis should be based on pathological results. [ABSTRACT FROM AUTHOR]

Bile duct hamartoma (BDH) is a rare liver disease with a rising incidence in recent years. A retrospective study on BDH patients between June 2007 and December 2015 was conducted. All the medical records, including clinical, imaging and pathological characteristics, were retrieved. Follow-up data were obtained by telephone communication. The majority of the patients had no symptoms and the laboratory tests were normal. The appearance on ultrasound examination was variable. The lesion exhibited low density on plain computed tomography and no enhancement in 4 cases, and inhomogeneous enhancement in 1 case. Magnetic resonance imaging examination revealed hypointensity on T1-weighted imaging (WI), hyperintensity on T2WI, no enhancement in 1 case, and enhancement in 4 cases. Two patients underwent magnetic resonance cholangiopancreatography due to jaundice and intrahepatic bile duct dilation. The preoperative diagnosis was liver cancer in 4 cases, hepatic hilar biliary obstruction in 1, chronic calculous cholecystitis in 1, suspected hepatic abscess in 1, and benign liver tumor in 2 cases. All the patients underwent surgery. Nest-like cell arrangements were observed in 2 patients, and in 1 patient the lesion transformed to intrahepatic cholangiocarcinoma, resulting in the patient's death 25 months after surgery. Thus, BDH may transform into a life-threatening cholangiocarcinoma and it should be surgically removed. Furthermore, the mechanism underlying carcinogenesis in BDH requires further investigation. [ABSTRACT FROM AUTHOR]

Background: Carcinoembryonic antigen (CEA) is one of the most widely used tumor markers and is increased in 30%-60% of patients with pancreatic cancer. Although carbohydrate antigen 19-9 (CA19-9) is the most important serum biomarker in pancreatic cancer, the diagnostic and prognostic value of CEA is gradually being recognized. Materials and methods: The MEDLINE, EMBASE, and Web of Science databases were searched for related literature published until January 2017. Diagnostic accuracy variables were pooled using the Meta-Disc software. The pooled hazard ratios (HRs) for prognostic data were calculated and analyzed using Stata software. Results: A total of 3,650 participants enrolled in 19 studies met our inclusion criteria. The pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of a CEA-based panel were 0.45 (95% confidence interval [CI], 0.41-0.50), 0.89 (95% CI, 0.86-0.91), 5.39 (95% CI, 3.16-9.18), and 0.55 (95% CI, 0.41-0.72), respectively. The area under the curve (AUC, 0.90) and Q-value (0.84) of the CEA-based panel indicated a significantly higher diagnostic accuracy compared with CEA or CA19-9 alone. Moreover, there was also a significant association between high levels of CEA and worse overall survival (HR, 1.43; 95% CI, 1.31-1.56). Conclusion: Our meta-analysis indicated that elevated serum CEA level, as a vital supplementary to CA19-9, can play an important role in the clinical diagnosis of pancreatic cancer patients and predict poor prognosis. [ABSTRACT FROM AUTHOR]

The present study aimed to determine the diagnostic concordance of plasma epidermal growth factor receptor (EGFR) mutation using droplet digital polymerase chain reaction (ddPCR) with tumor tissue samples and the predictive clinical significance of plasma EGFR mutation concentration. Plasma DNA samples from patients with non-small cell lung cancer (NSCLC) were analyzed for EGFR exon 21 codon 858 (L858R) mutation, deletion of exon 19 (ex19del) and exon 20 codon 790 (T790M) mutation using ddPCR. Firstly, the mutations in the plasma samples were compared with the matched tumor samples to determine the concordance. Secondly, image examination follow-ups were analyzed to assess the association between plasma EGFR mutation concentration and patients' response to EGFR-tyrosine kinase inhibitors (TKIs). A total of 51 patients with NSCLC were enrolled, including 48 newly diagnosed patients. Compared with tumor tissue samples, the sensitivity and specificity of ddPCR were 76.19% (16/21) and 96.55% (28/29) for mutant L858R, and 88.89% (8/9) and 100% (41/41) for ex19del, respectively. No patient exhibited the T790M mutation in the tumor tissue or plasma samples. Furthermore, 5 patients with the L858R mutation and 4 patients with ex19del in plasma and tumor tissue samples had been followed up with image examination for ≥3 months following EGFR-TKI treatment. The baseline mutant EGFR concentrations were positively correlated with a reduction in tumor burden (Spearman's r=0.7000, P=0.0358). When analyzed separately, ex19del concentrations (Spearman's r=1.0000, P<0.0001) were also positively correlated with the reduction, while mutant L858R concentrations were not (Spearman's r=0.7000, P=0.1881). In the present study, detection of plasma EGFR mutations using ddPCR exhibited sufficient concordance with tumor tissue sample results. Baseline plasma mutant EGFR and ex19del concentrations were significantly and positively correlated with response to EGFR-TKIs. [ABSTRACT FROM AUTHOR]

Aim Of Study: For the tumor lesions close to capsule of the liver, traditional percutaneous radiofrequency ablation (PRFA) is limited due to high incidence of postoperative complications. The aim of the present study is to whether laparoscopic combined with PRFA (LCPR) could effectively ablate the tumor lesions close to capsule of the liver.Methods: A total of 119 patients with subcapsular hepatocellular carcinoma (HCC) were divided into two groups: PRFA group (89 patients) and LCPR group (30 patients). RFA was accomplished through cool-tip RFA system. For LCPR, PRFA was first carried out to destroy tumors deep inside the liver tissue. Then, laparoscopic RFA was performed under the guide of laparoscopic view and destroyed the superficial part of the tumor. Postoperative morbidity and technique effectiveness between two groups were evaluated.Results: In PRFA group, the rate of fever was 70.8% (63/89), and two patients had gallbladder damage. Five patients had ascites. Pain was found in 26 patients (29.2%). In LCPR group, the rate of fever was 22/30 (73.3%). Two patients had ascites and only two patients complained of pain. In PRFA group, 77.5% (69/89) of the tumors were totally ablated, and in LCPR, 93.3% (28/30) of the tumors were destroyed without any residuals.Conclusion: LCPR could significantly reduce the incidence of postoperative pain and the rate of regional tumor residuals compared to the PRFA, suggesting this method could potentially be useful for subcapsular HCC ablation treatment. [ABSTRACT FROM AUTHOR]

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors originating in the gastrointestinal tract. With the introduction of molecular-targeted therapy for GISTs which has yielded remarkable outcomes, these tumors have become a model of multidisciplinary oncological treatment. Although Western clinical guidelines are available for GISTs, such as those published by the National Comprehensive Cancer Network (NCCN) and the European Society of Medical Oncology (ESMO), the clinical situations in Asian countries are different from those in Western countries in terms of diagnostic methods, surgical approach, and availability of new targeted agents. Accordingly, we have reviewed current versions of several GIST guidelines published by Asian countries (Japan, Korea, China, and Taiwan) and the NCCN and ESMO and discussed the areas of dissensus. We here present the first version of the Asian GIST consensus guidelines that were prepared through a series of meetings involving multidisciplinary experts in the four countries. These guidelines provide an optimal approach to the diagnosis and management of GIST patients in Asian countries. [ABSTRACT FROM AUTHOR]

Background: Gastric neuroendocrine neoplasms (G-NENs) are uncommon, and data on their management is limited. We here investigated the clinicopathological characteristics, surgical and survival outcomes in G-NENs among Chinese. Moreover, we will discuss their prognostic value.Methods: From existing databases of the West China Hospital, we retrospectively identified 135 consecutive patients who were surgically treated and pathologically diagnosed as G-NENs from January 2009 to August 2015.Results: This entire cohort comprised 98 males and 37 females, with a median age of 60 years. Twenty-five patients underwent endoscopic resection, while 110 patients underwent open/laparoscopic surgery. Thirty-nine patients had neuroendocrine tumor G1 (NET G1), seven patients had neuroendocrine tumor G2 (NET G2), 69 patients had neuroendocrine carcinoma G3 (NEC G3) and 20 patients had mixed adenoneuroendocrine carcinoma (MANEC). The median survival was not achieved for both NET G1 and NET G2 versus 19 months (range 3-48) for NEC G3 and 10.5 months (range 3-45) for MANEC. The 3-year survival rates for stage I, II, III, and IV were 91.1 %, 78.6 %, 51.1 % and 11.8 %, respectively (P < 0.001). As for the prognostic analysis, both surgical margin and the newly updated World Health Organization (WHO) classification were independent predictors of overall survival (OS).Conclusions: G-NENs are a kind of rare tumors, and patients with NET G3 and MANEC have unfavorable prognosis even surgically treated. Moreover, surgical margin and the new 2010 WHO criteria are closely associated with OS for G-NENs. [ABSTRACT FROM AUTHOR]

Primary lung enteric adenocarcinoma is a rare type of invasive lung carcinoma. Its morphology and immunohistochemistry are those of colorectal carcinoma, but there is no associated primary colorectal carcinoma. The present study describes the case of a 53-year-old female who presented with an irritating cough and a mass around the right sternoclavicular joint. Comprehensive evaluation revealed involvement of the mediastinum, lungs, right sternoclavicular joint and right kidney. Biopsies from the mediastinal and right sternoclavicular joint tumors showed features of adenocarcinoma. Immunohistochemistry was positive for cytokeratin (CK)20 and caudal type homeobox transcription factor 2, and negative for CK7, thyroid transcription factor-1 and napsin A. Genotypic analysis identified the expression of wild-type epidermal growth factor receptor, Kirsten rat sarcoma viral oncogene homolog, serine/threonine-protein kinase B-Raf and UDP-glucuronosyltransferase 1-1. There was no expression of echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase and a moderate expression of excision repair cross-complementation group 1, ribonucleoside-diphosphate reductase large subunit and tubulin β-3 chain. A strong expression of thymidylate synthase and 677TC genotype expression of methylenetetrahydrofolate reductase was observed. Gastroscopy, enteroscopy, colorectal colonoscopy and positron emission tomography-computed tomography failed to find evidence of a gastrointestinal malignancy and primary lung enteric adenocarcinoma was diagnosed. The presence of multiple metastases did not permit curative surgery. The patient was treated with 3 monthly cycles of the XELOX chemotherapy regimen; the response was poor with progression of supraclavicular lesions. Treatment was switched to the TP regimen for 4 monthly cycles, which resulted in a significant reduction in the size of the lung lesions; however, the supraclavicular lesion responded poorly to the treatment. The patient then received 2 cycles of the FOLFIRI regimen; however, the lung and right supraclavicular lesions progressed, causing increased right upper limb pain. The pain was alleviated by palliative surgery. Following surgery, the DP regimen was employed. Follow-up of the patient remains ongoing. The present findings suggest that the early diagnosis and treatment of primary lung enteric adenocarcinoma is likely to improve patient outcome. [ABSTRACT FROM AUTHOR]

Non-small-cell lung cancer (NSCLC) with echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) translocation is resistant to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), including gefitinib and erlotinib, but responds to the ALK-TKI crizotinib. Characterization of EML4-ALK translocation may provide invaluable information to facilitate disease diagnosis and improve the outcome of customized treatment. Although the occurrence of EML4-ALK translocation is likely to be affected by the smoking habits and gender of patients, the translocation has not been characterized extensively in female never-smokers with NSCLC. Therefore, 280 female never-smokers that were diagnosed with NSCLC were enrolled in the present study, and characteristics of EML4-ALK translocation, including the frequency, were determined in these NSCLC patients. EML4-ALK fusion variants were detected using Multiplex one-step reverse transcription-polymerase chain reaction and subsequently confirmed by DNA sequencing and Vysis ALK Break Apart fluorescence in situ hybridization analysis. The EML4-ALK fusion variants were detected in 21 carcinoma tissue specimens, accounting for 7.5% of the enrolled patients. Out of these patients with EML4-ALK fusion variants, EML4-ALK fusion variant 1 was identified in 12 patients, indicating that variant 1 is the most common type of EML4-ALK fusion gene in the present cohort of patients. ALK mRNA was aberrantly expressed in all the tissues with EML4-ALK translocation, but not in the carcinoma tissues without EML4-ALK translocation. In addition, the EML4-ALK translocation was more frequently found in younger patients. The median age of patients with EML4-ALK translocation was 50.95±2.29 years, which was significantly younger (P<0.01) than the median age of the patients without EML4-ALK translocation (57.15±0.56). The EML4-ALK translocation was detected exclusively in undifferentiated tumors that were graded as poorly- or moderately-differentiated carcinomas and suspected to be more malignant compared with well-differentiated tumors. In summary, the present study found that 7.5% of patients with NSCLC that are female never-smokers harbor EML4-ALK translocations, which are associated with the aberrant expression of ALK mRNA, early onset of disease and undifferentiated carcinomas. [ABSTRACT FROM AUTHOR]

Background: Primary gastric adenosquamous carcinoma (ASC) is a rare subset of ASC. This study aims to investigate the clinicopathological features, diagnosis, treatment, and outcomes of primary gastric ASC. Methods: The medical records of 13 consecutive patients with primary gastric ASC between January 2010 and July 2014 from a single institutional database were reviewed. Results: Male predominance was observed (M/F = 10/3) among the patients, and their median age was 62 years (range: 43 to 79 years). The primary lesions were most often found in the upper third of the stomach, with a median tumor size of 5 cm (range: 2.25 cm to 10.5 cm). Ten patients underwent radical resections (R0 resection, 76.9%), while three patients had palliative resections (R1/R2 resection, 23.1%). Twelve patients had lymph node metastasis at the time of surgery. Adenocarcinoma and squamous cell carcinoma components in lymph node were found in eight and two cases, respectively, while two patients had both squamous cell carcinoma and adenocarcinoma components. In terms of the TNM staging system, stages IIB, IIIA, IIIB, IIIC, and IV were detected in 2 (15.4%), 2 (15.4%), 1 (7.7%), 5 (38.5%), and 3 (23.1%) patients, respectively. The median follow-up period was 22 months (range: 5 to 52 months); during which, four patients were still alive and eight patients died because of tumor progression. The 1-, 2-, and 3-year survival rates were 76.9%, 46.2%, and 15.4%, respectively. Conclusions: Primary gastric ASC has a very poor prognosis, and both squamous cell carcinoma and adenocarcinoma components have distant metastasis potential. [ABSTRACT FROM AUTHOR]

Background and objective The fusion (rearrangement) of anaplastic lymphoma kinase (ALK) gene has been identified as an import factor to the tumorigenesis and development of lung cancer. ALK tyrosine kinase inhibitors (ALKTKIs) have been proved to have good effects to ALK positive lung cancers. The increasement of the relevance ratio of ALK will be very important to patients. The aim of this study is to investigate the clinical pathological features of ALK positive lung cancer, and the roles of immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in screening and confirming the ALK positive cases in the testing flow of ALK. Methods IHC analysis of ALK in tumor specimens was performed on 525 lung cancer patients. 34 cases among them were confirmed by FISH. Results The positive incidence of ALK by IHC was 5.14% (27/525). The ALK positive patients were significantly younger than ALK negative patients (P<0.05), and femal was predominant (P<0.05). The proportion of solid predominant adenocarcinoma was significantly higher in ALK positive patients (P<0.05). While acinar and lepidic predominant adenocarcinoma were significantly lower in ALK positive patients (P<0.05). FISH was applied in 34 cases. The coincidence rate was increased with the increasement of positive intensity of IHC staining. All the IHC positive cases with or without EGFR mutation must be confirmed by FISH. Conclusion IHC is a reliable detection method to screening the ALK in lung cancer, and then enhance the relevance ration. To make a definite diagnosis of ALK positive lung cancer, FISH is a significant detection method. [ABSTRACT FROM AUTHOR]