Melanotic Neuroectodermal Tumor of Infancy in the Epididymis: A Case Report.

Melanotic neuroectodermal tumor of infancy (MNTI) is a rare, benign neoplasm of neural crest origin that predominantly involves the craniofacial region, involvement of the epididymis being extremely rare, with about 30 cases reported. We report an unusual case of a 5-month-old male with MNTI in the epididymis. The patient underwent orchiectomy. Half a year later, there was no sign of recurrence. Whether preoperative examination or intraoperative frozen examination, the tumor may easily be misdiagnosed as malignancy. Melanotic neuroectodermal tumor of infancy should be included in differential diagnosis in infants presenting with fast-growing scrotal swelling.

From clinical variables to multiomics analysis: a margin morphology-based gross classification system for hepatocellular carcinoma stratification.

OBJECTIVE: Selecting interventions for patients with solitary hepatocellular carcinoma (HCC) remains a challenge. Despite gross classification being proposed as a potential prognostic predictor, its widespread use has been restricted due to inadequate studies with sufficient patient numbers and the lack of established mechanisms. We sought to investigate the prognostic impacts on patients with HCC of different gross subtypes and assess their corresponding molecular landscapes. DESIGN: A prospective cohort of 400 patients who underwent hepatic resection for solitary HCC was reviewed and analysed and gross classification was assessed. Multiomics analyses were performed on tumours and non-tumour tissues from 49 patients to investigate the mechanisms underlying gross classification. Inverse probability of treatment weight (IPTW) was used to control for confounding factors. RESULTS: Overall 3-year survival rates varied significantly among the four gross subtypes (type I: 91%, type II: 80%, type III: 74.6%, type IV: 38.8%). Type IV was found to be independently associated with poor prognosis in both the entire cohort and the IPTW cohort. The four gross subtypes exhibited three distinct transcriptional modules. Particularly, type IV tumours exhibited increased angiogenesis and immune score as well as decreased metabolic pathways, together with highest frequency of TP53 mutations. Patients with type IV HCC may benefit from adjuvant intra-arterial therapy other than the other three subtypes. Accordingly, a modified trichotomous margin morphological gross classification was established. CONCLUSION: Different gross types of HCC showed significantly different prognosis and molecular characteristics. Gross classification may aid in development of precise individualised diagnosis and treatment strategies for HCC.

Significance of FNAC, BRAF mutation, and intraoperative frozen section in surgical decision-making of thyroid nodules.

BACKGROUND: A preoperative method is desired to discriminate benign from malignant thyroid nodules. This retrospective study evaluated the diagnostic performance of BRAF (B-Raf proto-oncogene) mutation (BRAFV600E ) positivity and fine-needle aspiration cytology (FNAC) relative to intraoperative frozen section pathology. METHODS: Patients underwent preoperative FNAC of thyroid nodules. Cytology specimens were classified according to the Bethesda System for Reporting Thyroid Cytopathology (BSRTC), and analyzed for BRAFV600E using an amplification-refractory mutation system (ARMS). Thyroid tissue was surgically removed and frozen sections processed for histology. The sensitivities and specificities of each analysis were compared, alone and in combination. RESULTS: Among 346 patients, 333/358 FNACs (93%) showed malignant nodules; 322 (93%) patients received a pathological diagnosis of papillary thyroid carcinoma (PTC). The sensitivity and specificity of BSRTC VI for malignancy was the highest among the BSRTC categories. Compared with FNAC, the BRAFV600E analysis had significantly higher sensitivity and specificity. The diagnostic efficacy of frozen section pathology was significantly higher than that of either BSRTC category or BRAFV600E analysis alone. Combining methods variably improved diagnostic performance. BRAFV600E was not associated with capsule infiltration, neurovascular infiltration, mono- or multifocal PTC, lymph node metastasis, or clinical stage. CONCLUSION: The diagnostic performance of preoperative BRAFV600E determination was better than that of the BSRTC-FNAC category; combining both improved sensitivity and specificity. Patients with positive malignancy scores from both should be recommended for surgery; those with negative scores require close monitoring. Surgical treatment should include comprehensive intraoperative frozen section assessment. BRAF mutations cannot indicate aggressive treatment.

PTEN Expression Was Significantly Associated with PD-L1 Score but Not with EBV Infection in Gastric Cancer.

Purpose: Gastric cancer (GC) remains a prevalent aggressive tumor with high morbidity and mortality globally. The identification of GC subtypes based on molecular features improved the prediction of prognosis and the selection of targeted therapies. PTEN is a characteristic tumor suppressor, while its association with different GC subtypes was unknown. Patients and Methods: The cohort consisted of 248 patients diagnosed with gastric cancer who were hospitalized and received radical gastrectomy. In addition, PTEN gene expression matrix of STAD was retrieved from TCGA. The mRNA and protein levels of PTEN and PD-L1 were detected using qRT-PCR and IHC staining. Multivariate logistic regression and Kaplan-Meier analysis were used to examine the relationship between PTEN expression and clinical characteristics. Results: In our study, PTEN was downregulated in gastric tumors both in mRNA and protein levels. Its inactivation was closely linked to higher histological grade (P = 0.005), neural invasion (P = 0.012), depth of invasion (P = 0.021), lymph metastasis (P = 0.026), and TNM stage (P = 0.001) of GC in the present study. Moreover, according to the molecular subtypes, high PTEN expression was related to high TPS score of PD-L1 positively (P = 0.010) but was not associated with MSI and EBV infection. Further, TCGA data validated that PTEN was indeed correlated with histological grade and invasion depth and positively related to PD-L1 expression (R = 0.29, adjusted P < 0.001). Conclusion: The above results suggested that PTEN expression was a useful marker in gastric carcinogenesis and progression and in the selection of immunotherapy-based treatments for GC patients.

Lymphoepithelioma­Like Cholangiocarcinoma with Hepatitis C Virus Infection Treated by Microwave Ablation: A Literature Review and Case Report.

Background: Lymphoepithelioma-like cholangiocarcinoma (LELCC) is a rare type of intrahepatic tumor that is poorly understood. It is not associated with specific physical findings and is usually diagnosed incidentally, resulting in tumors that are often large-sized at diagnosis. At present, the main treatment approach is surgical resection. Case Presentation: Here, we report the case of a patient with LELCC treated with microwave ablation (MWA). Our patient was a Chinese man with chronic hepatitis C and a 51 mm-diameter intrahepatic tumor. Despite blood testing, gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging, and abdominal ultrasound, the tumor was not well diagnosed. However, the histopathological findings of ultrasound-guided percutaneous tumor biopsy led to a diagnosis of LELCC. The patient was treated with MWA, and no new lesions had occurred at 9 months after treatment. Conclusion: To our knowledge, this is the first patient with LELCC treated using MWA. Our experience suggests that MWA is an effective new therapeutic method for this disease.

Non-invasive evaluation of NAFLD and the contribution of genes: an MRI-PDFF-based cross-sectional study.

OBJECTIVE: To investigate the clinical, laboratory and genetic features of NAFLD patients based on MRI-PDFF in China. DESIGN: Patients with high ALT and with a diagnosis of fatty liver were included in this cross-sectional study. Fasting blood was collected to test biomarkers and SNPs. A total of 266 patients underwent MRI-PDFF and FibroScan examinations, and 38 underwent liver biopsy. Diagnostic models (decision tree, LASSO, and elastic net) were developed based on the diagnosis from MRI-PDFF reports. RESULTS: Approximately, 1/3 of the patients were found to have NASH and fibrosis. After quantifying liver steatosis by MRI-PDFF (healthy: n = 47; mild NAFLD: n = 136; moderate/severe NAFLD: n = 83; liver fat content (LFC): 3.6% vs. 8.7% vs. 19.0%), most biomarkers showed significant differences among the three groups, and patients without obesity were found to have a similar LFC as those with obesity (11.1% vs. 12.3%). Models including biomarkers showed strong diagnostic ability (accuracy: 0.80-0.91). Variant alleles of PNPLA3, HSD17B13 and MBOAT7 were identified as genetic risk factors causing higher LFC (8.7% vs. 12.3%; 11.0% vs. 14.5%; 8.5% vs. 10.2%, p < 0.05); those with the UQCC1 rs878639 variant allele showed lower LFC (10.4% vs. 8.4%; OR = 0.58, p < 0.05). Patients with more risk alleles had higher LFCs (8.1% vs. 10.7% vs. 11.6% vs. 14.5%). CONCLUSIONS: Based on MRI-PDFF, a combination of several specific biomarkers can accurately predict disease status. When the effects of genes on liver steatosis were first quantified by MRI-PDFF, the UQCC1 rs878639 G allele was identified as a protective factor, and the MBOAT7 T allele was identified as a risk only among nonobese individuals.

Application of propofol combined with sevoflurane anesthesia in staged hepatectomy liver detachment and portal vein ligation.

The aim of the present study was to investigate the application of propofol combined with sevoflurane anesthesia in associating liver partition and portal vein ligation for staged hepatectomy (ALPPS). A retrospective analysis of 40 patients with liver cancer who underwent ALPPS was performed. The study included 21 (control group) and 19 (observation group) patients who were administered propofol anesthesia and propofol in combination with sevoflurane anesthesia, respectively. Changes in liver function indicators, routine blood parameters and blood coagulation function, as well as cognitive function (mini-mental state examination) were recorded. The total bilirubin and direct bilirubin levels and the alanine aminotransferase (ALT) level after the first- and second-stage operation in the two groups was also higher than that prior to the first-stage operation (P<0.05), and the ALT level was significantly lower in the two groups after the second-stage operation compared with that prior to the second-stage operation (P<0.05). The AST level after the first- and second-stage operation was lower than that prior to the first- and second-stage operation, respectively (P<0.05). The white blood cell count after the second-stage operation was significantly lower compared with that prior to the second-stage operation (P<0.05). The plasma fibrinogen (FIB) level was higher after the first-stage operation compared with that prior to the first-stage operation (P<0.05). The prothrombin time in the two groups of patients was higher after the second-stage operation compared with that prior to the second-stage operation (P<0.05), whereas the FIB level was lower (P<0.05) and the international normalized ratio was not significantly different (P>0.05). The degree of cognitive decline prior to the first/second-stage operation, according to mini-mental state examination scores, was different from that after the first/second-stage operation (P<0.05). In conclusion, propofol combined with sevoflurane has a good application value in ALPPS.

[Retracted] miR­137 acts as a tumor suppressor in papillary thyroid carcinoma by targeting CXCL12.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the western blotting data shown in Figs. 4D and 5B were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in Oncology Reports 35: 2151-2158, 2016; DOI: 10.3892/or.2016.4604].

Microsatellite instability and Epstein-Barr virus combined with PD-L1 could serve as a potential strategy for predicting the prognosis and efficacy of postoperative chemotherapy in gastric cancer.

BACKGROUND: Microsatellite instability (MSI) and Epstein-Barr virus (EBV)-positive molecular subtypes exhibit complex immune responses in gastric cancer (GC), and PD-L1 has emerged as a prognostic biomarker associated with the cancer immune microenvironment. This study aimed to determine the prognostic value of molecular subtypes and whether the addition of PD-L1 would accurately predict the prognosis and guide postoperative chemotherapy for GC patients. METHODS: We performed molecular subtyping of tissue microarray slides from 226 GC patients who were treated with radical gastrectomy. The MSI status and PD-L1 expression were evaluated through immunohistochemistry (IHC) and EBV status through situ hybridization. Multiplex polymerase chain reaction (PCR) was also performed on 50 cases to validate the accuracy of IHC in defining MSI status. Differences in overall survival (OS) were assessed using the Kaplan-Meier method, log-rank test and Cox proportional hazards regression model. RESULTS: Among the 226 GC patients, 52 (23.2%) patients were classified as the MSI subtype, 11 (4.9%) were EBV+ subtype, and 161 (71.9%) were MSS (Microsatellite stable) /EBV subtype according to TCGA analysis. Two patients were both positive for MSI and EBV infection. EBV+ cases showed higher PD-L1 positivity than MSI cases and MSS/EBV cases (81.8% vs. 50.0% vs. 35.4%, P = 0.003). Compared with the non-MSS/EBV (MSI or EBV+ cases) subgroup, GC patients with MSS/EBV were associated with the worst outcomes (HR = 1.610, 95% CI [1.0462.479], P = 0.031). MSS/EBV GCs alone could benefit from postoperative chemotherapy (HR = 0.452, 95% CI [0.2990.682], P<0.001), and PD-L1-positive expression could also predict a better prognosis (HR = 0.612, 95% CI [0.3890.962], P = 0.033) in this subgroup. Considering both chemotherapy efficacy and PD-L1 expression in the MSS/EBV subgroup, chemotherapy could improve the prognosis for PD-L1-negative MSS/EBV GCs (HR = 0.357, 95% CI [0.2170.587], P <0.001) but not PD-L1-positive MSS/EBV GCs. CONCLUSIONS: Molecular subtyping combined with PD-L1 expression could serve as a potential strategy to better predict prognosis and guide postoperative chemotherapy of GC patients.

miR-383 reduces keratinocyte proliferation and induces the apoptosis in psoriasis via disruption of LCN2-dependent JAK/STAT pathway activation.

Psoriasis is a chronic and relapsing disorder with considerable negative effects on patients' quality of life. The finer details associated with the molecular mechanism of psoriasis and its pathogenesis remain somewhat elusive. Extensive studies have highlighted the crucial role of microRNAs (miRNAs) in the development of psoriasis. Hence, the current study aimed to investigate the effect of miR-383 on a psoriasis rat model and elucidate the underlying molecular mechanism. The rat psoriasis model was established via imiquimod (IMQ) induction followed by verification of miR-383 and LCN2 expression in the skin tissues of the models. ELISA was conducted to determine the secretion of inflammatory factors. Keratinocyte proliferation and apoptosis was evaluated by MTT assay and flow cytometric analysis. Down-regulation of miR-383 and up-regulation of LCN2 were detected in the psoriasis rat model. Our data indicated that miR-383 targeted LCN2 by binding to its 3'UTR and inhibited JAK/STAT pathway activation. Notably, miR-383 overexpression or LCN2 knockdown attenuated psoriasis-like symptoms, suppressed inflammatory response, reduced the expression of JAK3 and STAT3, ceased keratinocyte proliferation, and promoted the apoptosis. The findings of our study suggest that miR-383 may inhibit LCN2 and inactivate the JAK/STAT pathway, suppressing the progression of psoriasis in a rat model. This study provided novel insights into the pathogenesis of psoriasis and offered potential targets for psoriasis treatment.

SELE Downregulation Suppresses Mast Cell Accumulation to Protect against Inflammatory Response in Chronic Idiopathic Urticaria.

BACKGROUND: Chronic idiopathic urticaria (CIU) represents a common skin disorder often characterized by mast cell activation and secretion of histamine and other proinflammatory factors. E-selectin (SELE) has been implicated in the pathogenesis of common inflammatory cutaneous disorders, while the role of SELE in CIU is yet to be fully understood. Thus, we aimed to investigate the mechanism by which SELE influences CIU in connection with the involvement of mast cells. METHODS: SELE expression was measured in blood samples obtained from CIU patients and normal individuals. A CIU mouse model was subsequently established by intradermally injecting a normal saline solution with ovalbumin IgE antiserum into the mice. Loss- and gain-of-function investigations were conducted on the mouse models. The number of degranulated mast cells and the amount of histamine release in vitro were determined. The levels of SELE, tumor necrosis factor (TNF)-α, homologous restriction factor (HRF), and interleukin (IL)-6 levels were determined. RESULTS: The CIU clinical samples exhibited upregulated SELE, while the CIU mice showed increased mast cell degranulation and an increased rate of histamine directional release, as well as an elevated expression of SELE, TNF-α, HRF, and IL-6. SELE silencing was found to decrease the number of degranulated mast cells and reduce the rate of histamine directional release, along with suppressed TNF-α, HRF, and IL-6 expression, in the serum of CIU mice. Ketotifen was observed to rescue the increased expression of TNF-α, HRF, and IL-6 caused by SELE overexpression. CONCLUSIONS: This study highlights the potential of SELE downregulation to repress inflammatory factor secretion caused by the accumulation of mast cells, which ultimately inhibits the development of CIU.

Predictive Factors of Central-Compartment Lymph Node Metastasis for Clinical N0 Papillary Thyroid Carcinoma With Strap Muscle Invasion.

Background: Papillary thyroid carcinoma (PTC) patients with anterior extrathyroidal extension (ETE) involving the strap muscle have a relatively better prognosis than those with posterior gross ETE involving the recurrent laryngeal nerve. Whether prophylactic central-compartment lymph node dissection (CLND) should be performed in PTCs with only strap muscle invasion (SMI) is still unclear. Methods: A retrospective cohort study was conducted in clinical N0 (cN0) PTC patients with SMI who underwent thyroid surgery from 2009 to 2017. A total of 152 patients were included, and predictive factors of central-compartment lymph node metastasis (CLNM) were determined. Results: Among the 281 PTCs patients with SMI, 152 (51.1%) did not clinically present with lymph node metastasis. Microscopic CLNM was identified in 77 (50.7%) cN0 PTC patients with SMI. According to the univariate and multivariate analyses, male patients and those aged <40 years were more likely to be diagnosed with CLNM than female patients and those aged >40 years (odds ratio [OR] = 6.22 [95% confidence interval (CI), 1.43-27.10], p = 0.02 vs. OR = 9.94 [95% CI, 2.79-35.44], p = 0.00). The CLNM positive rate of male patients aged <40 years was 87.5%, while that for female patients aged ≥55 years was 23.8%. However, risk factors associated with large-volume CLNM were not identified because of the small number of patients. Conclusions: Taken together, nearly half of PTC patients with SMI did not clinically present with lymph node metastasis. Male sex and patients aged <40 years were identified as the predictive factors of CLNM in cN0 PTCs with SMI. Hence, the results of this single-center study raise the possibility that prophylactic CLND may be more often considered for younger male PTC patients with SMI.

Galectin-3 not Galectin-9 as a candidate prognosis marker for hepatocellular carcinoma.

BACKGROUND: Galectins (Gal) are a family of protein that bind to the ß-galactoside of glycoproteins. It modulates a variety of biological functions, such as tumor growth, angiogenesis and tumor metastasis. A series of experimental and clinical evidences have been reported to support a correlation between galectin expressions and neoplastic transformation, progression and prognosis. The objective of this study was to estimate the expression of Gal-3 and Gal-9 in order to evaluate their relation to hepatocellular carcinoma (HCC) -related clinical features and their prognostic values. METHODS: We evaluated Gal-3 and Gal-9 expression in 247 HCC patients by a tissue microarray immunohistochemistry method, then analyzed the relationship between expression levels of Gal-3 and Gal-9 protein and tumor parameters or clinical outcomes. RESULTS: The Gal-3 expression was significantly higher in tumor tissues compared with adjacent non-tumor tissues (P < 0.001), while no significant differences of Gal-9 was detected (P = 0.222). A higher Gal-3 expression was significantly associated with lymph-vascular invasion (P = 0.049), poor histological differentiation (P = 0.016), and no cirrhosis (P = 0.040). In contrast, a lower Gal-9 expression was related to lymph-vascular invasion (P = 0.012) and poor histological differentiation (P = 0.002). Survival analysis showed that patients with higher Gal-3 expression had worse overall survival (P = 0.012) , however no correlation was found between Gal-9 expression and survival (P = 0.185). Multivariate analysis showed that multiple tumor (HR = 1.94, 95% CI [1.36-2.78]), tumor size ≥ 5 cm (HR = 1.51, 95% CI [1.07-2.12]), Lymph-vascular invasion (HR = 1.45, 95% CI [1.00-2.10]) and Gal-3 expression (HR = 1.57, 95% CI [1.06-2.33]) were independent influencing factors of prognosis in patients with hepatocellular carcinoma. CONCLUSION: Gal-3 was expected to serve as a novel prognostic marker of hepatocellular carcinoma, while Gal-9 expression was only related to tumor progression.

Silencing of hsa_circ_0101145 reverses the epithelial-mesenchymal transition in hepatocellular carcinoma via regulation of the miR-548c-3p/LAMC2 axis.

Hepatocellular carcinoma (HCC) is a primary cause of cancer-related deaths globally. While there have been advancements in HCC treatment and diagnosis, incidence and mortality rates continue to rise. One study found that circular RNAs functioned as competing endogenous RNAs, and constructed a gene-based nomogram to estimate overall survival of HCC patients. Previous studies using high-throughput sequencing suggested that hsa_circ_0101145 is abnormally expressed in HCC, but the underlying mechanism is unknown. We performed RT-qPCR to determine hsa_circ_0101145 and miR-548c-3p expression in HCC tissues. We used fluorescence in situ hybridization (FISH) to detect hsa_circ_0101145 expression and hsa_circ_0101145 subcellular localization in HCC tissues. hsa_circ_0101145 expression in HCC cells was selectively regulated. We determined LAMC2 and EMT mRNA and protein levels by RT-qPCR and western blotting analysis, respectively. We employed flow cytometry, and CCK8, Transwell, and wound healing assays to monitor the cell cycle, cell proliferation, invasion, and migration, respectively. We employed dual-luciferase reporter and RNA pulldown assays to verify the relationship among hsa_circ_0101145, miR-548c-3p, and LAMC2. We examined the effects of hsa_circ_0101145 on HCC cell metastasis and proliferation in vivo using a subcutaneous xenograft model as well as intravenous tail injection of nude mice. The data demonstrated that hsa_circ_0101145 was significantly upregulated in both HCC tissues and cell lines. High hsa_circ_0101145 expression was correlated with aggressive HCC phenotypes. Downregulation of hsa_circ_0101145 suppressed HCC proliferation as well as metastasis by targeting the miR-548c-3p/LAMC2 axis, which was examined using luciferase reporter and RNA pulldown assays. Silencing of hsa_circ_0101145 suppressed the epithelial-mesenchymal transition in HCC. Downregulation of miR-548c-3p or overexpression of LAMC2 restored migration and proliferation abilities of HCC cells following hsa_circ_0101145 silencing. LAMC2 overexpression reversed miR-548c-3p-induced cell migration and growth inhibition in vitro. In summary, the findings illustrated that hsa_circ_0101145 silencing suppressed HCC progression by functioning as an miR-548c-3p sponge to enhance LAMC2 expression. Therefore, hsa_circ_0101145 could be an HCC treatment target.

Thyroid metastasis from breast cancer presenting with enlarged lateral cervical lymph nodes: A case report.

BACKGROUND: Secondary malignancy of the thyroid occurs infrequently and mainly originates from malignant tumors of the kidney, gastrointestinal tract, lungs, breast, and skin. The correct diagnosis is important but difficult. Importantly, there are major differences in the treatment of primary and metastatic thyroid cancer, which has a significant impact on prognosis and survival. Therefore, how to diagnose thyroid metastasis (TM) correctly before surgery is a major concern for surgeons. CASE SUMMARY: We report a 38-year-old woman who presented with palpable cervical lymph nodes after breast cancer (BC) surgery 2 years ago. Ultrasonography and computed tomography revealed thyroid nodules with irregular margins and enlarged cervical lymph nodes. Biopsy was performed for the right largest cervical lymph node, and immunohistochemical analysis revealed negativity for thyroglobulin, estrogen receptor, and progestin receptor and positive for human epidermal growth factor receptor 2. The diagnosis was TM from BC with cervical lymph node metastasis. Total thyroidectomy with bilateral central and lateral neck lymph node dissection was performed. After a 5-mo follow-up, no recurrence or novel distant metastasis was identified. CONCLUSION: TM from BC is a rare secondary malignancy. Broad differential diagnosis by biopsy and immunohistochemical analysis needs to be considered.

Routine Lateral Level V Dissection May Not Be Necessary for Papillary Thyroid Microcarcinoma With Lateral Lymph Node Metastasis: A Retrospective Study of 252 Cases.

Background: Lateral lymph node metastasis (LLNM) is associated with distant metastasis, locoregional recurrence and cancer-specific mortality, although the prevalence of LLNM among patients with papillary thyroid microcarcinoma (PTMC) is relatively low. The potential benefits and risks of routine lateral level V dissection (LVD) for PTMC with LLNM have not been previously investigated. Methods: A total of 6,880 consecutive PTMC patients who underwent initial surgery at the First Hospital of Jilin University from January 2009 to July 2017 were retrospectively analyzed. A total of 252 N1b PTMC patients were enrolled in our study. Results: The overall and occult metastasis rates in level V lymph nodes were 21.4 and 6.4%, respectively. Patients with N1b PTMC who received LVD did not show a significantly lower disease-free survival (DFS) than that of patients who did not receive LVD [hazard ratio = 1.11 (CI 0.38-3.21); p = 0.85]. Meanwhile, LVD simultaneously increased the hospital stay and cost (p = 0.03; 0.02). Multivariate logistic regression analysis revealed that 3-level simultaneous metastasis in the lateral neck was an independent risk factor for level V metastasis [odds ratio = 8.6 (CI 1.42-51.72); p = 0.02]. Conclusions: Because of the low metastasis rate in level V lymph nodes, the lack of benefit for recurrence, the longer hospital stay and the higher cost associated with LVD, N1b PTMC patients without clinical level V metastasis may not need to undergo routine dissection. Prophylactic LVD may be recommended only for patients with N1b PTMC with 3-level simultaneous metastasis.

Predictive Factors of Recurrence for Multifocal Papillary Thyroid Microcarcinoma With Brafv600e Mutation: A Single Center Study of 1,207 Chinese Patients.

Background: The American Thyroid Association (ATA) guidelines risk stratify Brafv600e mutated multifocal papillary thyroid microcarcinoma (BMPTMC) into different recurrence risk groups by the extent of extrathyroidal extension (ETE). These findings and modifications for BMPTMC need to be verified in additional studies. Methods: A retrospective cohort study was conducted in BMPTMC patients who underwent total thyroidectomy (TT) and central lymph node dissection (CLND) from 2008 to 2013. Overall, 1,207 patients were included, and predictive factors were identified by univariate and multivariate analysis over a mean 7.5-year follow up. Results: BMPTMC with ETE to capsule shows the same recurrence rate (3.8%) with intrathyroidal BMPTMC. Moreover, BMPTMC with ETE only to strap muscle, which belongs to high-risk group according to ATA guideline, shows relatively lower recurrence rate (13.3%) compared with some intermediate risk categories such as cN1 and >5 pN1. Multivariate analysis using a Cox proportional hazards regression model shows that total tumor diameter (TTD) is associated with significantly higher recurrence for BMPTMC with or without other risk factors (Hazard Ratio (HRO) = 9.86 [95%CI 5.35-18.20], p = 0.00; HRO = 2.32 [95%CI 1.12-4.85], p = 0.02; respectively), while Hashimoto thyroiditis (HT) is found to be protective against the recurrence (HRO = 0.51 [95%CI 0.33-0.79], p = 0.00; HRO = 0.47 [95%CI 0.25-0.89], p = 0.02; respectively). Conclusions: Taken together, capsular ETE and gross ETE to the strap muscles did not have the expected significant influence on recurrence for Chinese BMPTMC patients who underwent TT and CLND. Rather than the extent of ETE, TTD and the lack of HT were identified as predictors for recurrence among BMPTMC with or without other risk factors (vascular invasion, cN1, pN1>5, pN1>3 cm).

Congenital hepatic fibrosis with polycystic kidney disease: Two case reports.

INTRODUCTION: Congenital hepatic fibrosis (CHF) is a rare autosomal recessive disease derived from biliary dysgenesis secondary to ductal plate malformation and is often accompanied by renal cysts or increased renal echogenicity. PATIENT CONCERNS: A 25-year-old woman was admitted to our hospital with splenomegaly and hepatic cirrhosis of a 3-month duration and fever accompanied by abdominal pain for 3 days. The second patient was a 25-year-old male referred to our hospital with hepatomegaly and splenomegaly of 6-year duration who had experienced fever for 3 months and abdominal distension for 1 week. Both 25-year-old patients were found to have CHF with polycystic kidney disease. DIAGNOSIS: Radiological imaging, including computed tomography (CT), magnetic resonance imaging (MRI), and sonography, revealed hepatic fibrosis, portal hypertension, splenomegaly, ascites, bile duct malformation, polycystic kidneys, and CHF. For the first patient, a liver biopsy confirmed the pathological features of CHF, and genetic testing revealed three heterozygous missense mutations, which were classified as "undetermined" in the public Wilson's disease/ATP7B and ADPKD/PKD1 databases. INTERVENTIONS: The first patient had undergone a splenectomy for anemia 2 months previously. Because there is no radical cure for CHF, and due to economic reasons, neither patient received liver transplantation. Therefore, we administered only anti-fibrotic supportive treatment for symptoms. OUTCOMES: Both patients were discharged after their symptoms improved, and both survived for 2 years of follow-up. CONCLUSION: These cases highlight the value of radiological imaging, pathological examination, and genetic evaluation for the diagnosis of CHF. When an individual with unexplained cirrhosis presents with bile duct dilation and malformation as well as polycystic kidneys, the possibility of CHF should be considered. For individuals found to have polycystic kidneys at a young age, the results of liver function tests and imaging examinations including Fibroscan imaging should be continuously and dynamically monitored to enable early diagnosis of CHF.

Lethal-7-related polymorphisms are associated with susceptibility to and prognosis of gastric cancer.

BACKGROUND: The lethal-7 (let-7) family members and their targets are involved in the development and progression of tumors. Let-7-related polymorphisms have been reported to be associated with tumorigenesis and prognosis. In gastric cancer, however, the related studies are limited. AIM: To investigate the role of let-7-related microRNA polymorphisms in the tumorigenesis and prognosis of gastric cancer in a Chinese population. METHODS: A total of 898 gastric cancer patients and 992 tumor-free controls were recruited into this study from 2008 to 2013. Gastric cancer patients were followed periodically. Ten single nucleotide polymorphisms (SNPs) in the let-7 gene region or their target mRNAs were genotyped using the MassARRAY system and their associations with the risk for or overall survival of gastric cancer were analyzed. RESULTS: All the ten SNPs were in Hardy-Weinberg equilibrium. The C allele of the rs3811463 polymorphism in the 3'-untranslated region (UTR) of LIN28A was associated with a lower risk of gastric cancer [odds ratio (OR) = 0.74, 95% confidence interval (CI): 0.61-0.88, P = 0.001] after adjustment for age and Helicobacter pylori status. Seven hundred and thirty-five gastric cancer patients who had undergone radical tumorectomy were included in the survival analysis and their 5-year survival rate was 53.9% (95%CI: 50.1%-57.6%). The rs10889677 in the 3'-UTR of IL23R was corresponded to the prognosis of gastric cancer in a dose-response manner, in which the death risk increased by 25% [hazard ratio (HR) = 1.25, 95%CI: 1.04-1.45, P = 0.011] with each increase in the number of C alleles after controlling for other potential clinicopathological parameters. CONCLUSION: The let-7-related polymorphism rs3811463 in LIN28A is associated with the susceptibility to gastric cancer and the let-7-related polymorphism rs10889677 in IL23R is associated with the prognosis of gastric cancer.

Tetramethylpyrazine Protects Against Early Brain Injury and Inhibits the PERK/Akt Pathway in a Rat Model of Subarachnoid Hemorrhage.

Neuronal apoptosis is a potentially fatal pathological process that occurs in early brain injury (EBI) after subarachnoid hemorrhage (SAH). There is an urgent need to identify effective therapeutics to alleviate neuronal apoptosis. Tetramethylpyrazine (TMP), as an important component of the Chinese traditional medicinal herb Ligusticum wallichii, has been widely used in China to treat cerebral ischemic injury and confer neuroprotection. In the present work, we investigate whether TMP can reduce EBI following SAH in rats, specifically via inactivating the PERK/Akt signaling cascade. One hundred twenty-five male Sprague-Dawley rats were used in the present study. TMP was administered by intravenous (i.v.) injection, and the Akt inhibitor MK2206 was injected intracerebroventricularly (i.c.v.). SAH grade, neurological scores, and brain water content were measured 24 h after SAH. Neuronal apoptosis was visualized by Fluoro-Jade C (FJC) staining. Western blotting was used to measure the levels of PERK, p-PERK, eIF2α, p-eIF2α, Akt, p-Akt, Bcl-2, Bax, and cleaved caspase-3. Our results showed that TMP effectively reduced neuronal apoptosis and improved neurobehavioral deficits 24 h after SAH. Administration of TMP reduced the abundance of p-PERK and p-eIF2α. In addition, TMP increased the p-Akt level and the Bcl-2/Bax ratio and decreased the level of cleaved caspase-3. The selective Akt inhibitor MK2206 abolished the anti-apoptotic effect of TMP at 24 h after SAH. Collectively, these results indicate that Akt-related anti-apoptosis through the PERK pathway is a major, potent mechanism of EBI. Further investigation of this pathway may provide a basis for the development of TMP as a clinical treatment.