Basal Cell Adenoma With Atypia in the Nasal Cavity Mimicking a Malignant Tumor.

Basal cell adenomas (BCA) arising from the nasal cavity or paranasal sinuses are very rare. A 64-year-old male patient was suspected of having a malignant tumor after undergoing preoperative computed tomography scans and magnetic resonance imaging. The intraoperative frozen section showed a malignant tumor; however, the final diagnosis revealed BCA with atypia, tubular pattern.

Comparison of histological and molecular features of pediatric-type follicular lymphoma and pediatric nodal marginal zone lymphoma.

Pediatric-type follicular lymphoma and pediatric nodal marginal zone lymphoma are pediatric B cell lymphomas with similar clinical characteristics but distinct histological features. We investigated the differences between pediatric-type follicular lymphoma and pediatric nodal marginal zone lymphoma by comparing their histological and molecular characteristics. A total of 5 pediatric-type follicular lymphoma and 11 pediatric nodal marginal zone lymphoma patients were included in the study. In the histological review, 5 of the 16 cases showed overlapping morphological features of pediatric-type follicular lymphoma and pediatric nodal marginal zone lymphoma; hence, they were reclassified as "mixed type." In molecular analysis, using panel-based massively parallel sequencing, MAP2K1, TNFRSF14, and IRF8 mutations were found in 6, 3, and 2 of the 11 pediatric nodal marginal zone lymphoma patients, respectively, and IRF8 mutation was found in one of the five pediatric-type follicular lymphoma patients. There were no significant differences in genetic alterations established from the histologically reclassified diagnosis as well as the initial diagnosis. Pediatric-type follicular lymphoma and pediatric nodal marginal zone lymphoma showed morphological overlap in some cases, and no difference between the two was found upon molecular analysis. These findings suggest the possibility that pediatric-type follicular lymphoma and pediatric nodal marginal zone lymphoma are single entity pediatric B-cell lymphoma with broad morphological spectrum.

Local Critic Training for Model-Parallel Learning of Deep Neural Networks.

In this article, we propose a novel model-parallel learning method, called local critic training, which trains neural networks using additional modules called local critic networks. The main network is divided into several layer groups, and each layer group is updated through error gradients estimated by the corresponding local critic network. We show that the proposed approach successfully decouples the update process of the layer groups for both convolutional neural networks (CNNs) and recurrent neural networks (RNNs). In addition, we demonstrate that the proposed method is guaranteed to converge to a critical point. We also show that trained networks by the proposed method can be used for structural optimization. Experimental results show that our method achieves satisfactory performance, reduces training time greatly, and decreases memory consumption per machine. Code is available at https://github.com/hjdw2/Local-critic-training.

Primary pleural epithelioid angiosarcoma manifesting as a loculated hemothorax: A case report and literature review focusing on CT findings.

Primary pleural angiosarcoma (PPA) is an extremely rare and clinically aggressive tumor. We report the case of a 66-year-old man having PPA with chest computed tomography (CT) scan showing a large oval-shaped, nonenhancing high attenuation cystic mass in the left hemithorax. Morphological and immunohistochemical findings supported the diagnosis of epithelioid angiosarcoma. Pleural angiosarcoma should be considered in the differential diagnosis of spontaneous hemothorax manifesting as high attenuation loculated pleural fluid on CT.

Low PDCD4 Expression Is Associated With Poor Prognosis of Colorectal Carcinoma.

Programmed cell death 4 (PDCD4) is a tumor suppressor gene that inhibits tumor progression, invasion, and metastasis. Decreased PDCD4 expression is associated with poor prognosis in various types of cancers. We evaluated PDCD4 expression and its clinicopathologic correlation, including patient survival, in 289 surgically resected colorectal cancers. Low nuclear PDCD4 expression was identified in 177 (61.2%) cases and was associated with large tumor size, high pT classification, and the presence of lymphovascular and perineural invasion. The 5-year survival rate of patients with low nuclear PDCD4 expression was significantly lower than that of patients with high expression (72.2% vs. 93.3%, P<0.001). American Joint Committee on Cancer stage II and III colorectal cancer patients with low nuclear PDCD4 expression (76.9% and 67.2%, respectively) showed significantly worse overall survival than those with high expression (100% and 92.9%, P=0.002 and 0.032, respectively). Low nuclear PDCD4 expression was an independent poor prognostic factor in colorectal cancer patients (hazard ratio=3.556; 95% confidence interval, 1.739-7.271; P=0.001). Our study suggests that low PDCD4 expression is associated with aggressive behavior and can be used as a prognostic indicator of colorectal cancer patients.

VGLL4 with low YAP expression is associated with favorable prognosis in colorectal cancer.

The Hippo pathway is a tumor suppressive pathway regulating Yes-associated protein-TEA domain-containing sequence-specific transcription factor (YAP-TEAD) complex. VGLL (Vestigial-like) proteins are transcriptional cofactors competing with YAP for TEAD binding and interfering oncogenic activity of YAP-TEAD complex. We evaluated the expression of VGLL4, YAP, and TEAD4 and assessed their correlations with clinicopathologic factors and prognostic effects in 295 colorectal cancers. VGLL4 was positive in 164 (55.6%) cases and correlated with small tumor size, low pT classification, and absence of lymph node metastasis. YAP and TEAD4 were highly expressed in 138 (46.8%) cases and 144 (48.8%) cases, respectively, and high expressions were associated with presence of lymphovascular invasion and lymph node metastasis, or distant metastasis. VGLL4 expression was significantly correlated with low YAP expression (p < 0.001) and had significantly better overall survival than negative expression (p < 0.001). High YAP (HR, 2.108; 95% confidence interval, 1.239-3.584; p = 0.006) and TEAD4 (1.724; 1.021-2.912; p = 0.042) expressions were associated with poor overall survivals. The combined VGLL4pos YAPlow expression showed the best overall survival than other groups (p < 0.001). VGLL4 expression (0.381; 0.212-0.683; p = 0.001) and combined VGLL4pos YAPlow expression (0.227; 0.108-0.475; p < 0.001) were independent good prognostic factors in colorectal cancers. The expressions of VGLL4, YAP, and TEAD4 can be used as prognostic markers in colorectal cancer patients.

Different expression of GSK3ß and pS9GSK3ß depending on phenotype of cervical cancer: possible association of GSK3ß with squamous cell carcinoma and pS9GSK3ß with adenocarcinoma.

OBJECTIVE: This study aimed to analyze the expression pattern of glycogen synthase kinase 3ß (GSK3ß) and its phosphorylated forms, GSK3ß phosphorylated at Ser9 (pS9GSK3ß), and GSK3ß phosphorylated at Tyr216 (pY216GSK3ß), in cervical squamous cell carcinoma (SCC) and adenocarcinoma (AC). METHODS: We performed immunohistochemical staining for GSK3ß, pS9GSK3ß, and pY216GSK3ß in 64 SCC and 20 AC cases and compared their expression patterns between the 2 tumor types. RESULTS: Increased GSK3ß and pS9GSK3ß expression but decreased pY216GSK3ß expression compared with that in the normal cervix were observed in both SCC and AC specimens. Specifically, the levels of GSK3ß and pS9GSK3ß were significantly increased in SCC and AC, respectively. GSK3ß was localized in the nucleus and/or cytoplasm of SCC and AC cells. However, pS9GSK3ß was predominantly localized in the membrane of AC cells, whereas it was present in the nucleus and/or cytoplasm of SCC cells. CONCLUSION: The results suggest that the phosphorylation status of GSK3ß changes during cervical cancer development and the different expression levels and patterns of GSK3ß and pS9GSK3ß are associated with the specific histologic phenotype of cervical cancer.

Herbal medicine (Hyeolbuchukeo-tang or Xuefu Zhuyu decoction) for treating primary dysmenorrhea: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Primary dysmenorrhea is a condition characterized by painful menstrual cramps that usually occurs in the absence of any identifiable pathological condition among menstruating women, with the prevalence estimates varying between 45% and 95%. Nonsteroidal anti-inflammatory drugs (NSAIDs) are considered as a standard treatment for primary dysmenorrhea; however, the failure rate of NSAIDs is often 20% to 25% and these drugs commonly cause adverse effects. In this review, we investigated the current evidence related to the effectiveness of Xuefu Zhuyu decoction (XZD) or Hyeolbuchukeo-tang, a traditional herbal formula, as a treatment for primary dysmenorrhea. METHODS: Literature search was conducted about randomized controlled trials (RCTs) for XZD on primary dysmenorrhea. PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure Database, Oriental Medicine Advanced Searching Integrated System, and other Chinese, Korean, Japanese databases were searched up to December 20, 2017. Two independent reviewers extracted and assessed the data. The main outcome domains were visual analogue scale (VAS) score and response rate. RESULTS: Among 475 publications, 8 RCTs involving 1048 patients were finally included. Methodological quality of included RCTs was relatively low. In 4 add-on design studies, XZD plus western medication (WM) group showed better response rate as compared to the WM sole therapy (relative risk 1.18, 95% confidence interval [1.11, 1.25], P < .01). VAS score after the 3rd month of treatment in the XZD plus WM group was also lower than that in the WM group (mean difference -0.45, 95% confidence interval [-0.79, -0.12], P < .01). In 4 XZD versus WM design studies, XZD sole therapy showed better response rate than did WM sole therapy (relative risk 1.26, 95% confidence interval [1.06, 1.49], P < .01). CONCLUSION: The existing trials showed a favorable effect of XZD for the management of primary dysmenorrhea. However, the efficacy of XZD on primary dysmenorrhea is not conclusive owing to the small number of studies and the high risk of bias. Large-scale, long-term RCTs with rigorous methodological input are needed to clarify the role of XZD for the management of primary dysmenorrhea. TRIAL REGISTRATION NUMBER: CRD42016050447 in PROSPERO 2016.

Acupuncture for Infantile Colic: A Systematic Review of Randomised Controlled Trials.

INTRODUCTION: Infantile colic is a common condition causing considerable deterioration in the quality of life of both infants and their parents. Minimal acupuncture, a gentle needling technique without strong muscle stimulation, has primarily been used to treat this condition, but the clinical evidence of its efficacy and safety is yet to be established. The objective of this review was to assess clinical evidence of the safety and efficacy of acupuncture for infantile colic. METHODS: To identify studies for inclusion, PubMed, Cochrane Library, Google Scholar, China Knowledge Resource Integrated Database, Wanfang, and Oriental Medicine Advanced Searching Integrated System were searched until January 2017. Only randomised controlled trials of infantile colic in patients aged 0 to 25 weeks, who were treated with acupuncture, were included. To assess the quality, the risk of bias was determined for each study by two authors. The intention was to perform a meta-analysis, but this was not possible in this study due to considerable clinical heterogeneity among the included studies. RESULTS: Of the 601 studies identified, only four randomized controlled trials were included in this review. All included studies were conducted in northern European countries. Most studies showed a low risk of bias in most domains. Minimal acupuncture on LI4 or ST36 without strong stimulation was used in all studies. From the narrative analysis, acupuncture appears to be effective in alleviating the symptoms of colic, including crying and feeding and stooling problems, and may have only minor adverse effects. However, clinical evidence could not be confirmed owing to considerable clinical heterogeneity and the small sample sizes of the included studies. CONCLUSION: There is currently no conclusive evidence on the safety and efficacy of acupuncture for infantile colic. Rigorous full-scale randomized controlled trials will be necessary in future.

The efficacy and safety of acupuncture in women with primary dysmenorrhea: A systematic review and meta-analysis.

BACKGROUND: This systematic review aimed to evaluate the current evidence regarding the efficacy and safety of acupuncture on primary dysmenorrhea. METHODS: Ten electronic databases were searched for relevant articles published before December 2017. This study included randomized controlled trials (RCTs) of women with primary dysmenorrhea; these RCTs compared acupuncture to no treatment, placebo, or medications, and measured menstrual pain intensity and its associated symptoms. Three independent reviewers participated in data extraction and assessment. The risk of bias in each article was assessed, and a meta-analysis was conducted according to the types of acupuncture. The results were expressed as mean difference (MD) or standardized mean difference (SMD) with 95% confidence intervals (CIs). RESULTS: This review included 60 RCTs; the meta-analysis included 49 RCTs. Most studies showed a low or unclear risk of bias. We found that compared to no treatment, manual acupuncture (MA) (SMD = -1.59, 95% CI [-2.12, -1.06]) and electro-acupuncture (EA) was more effective at reducing menstrual pain, and compared to nonsteroidal anti-inflammatory drugs (NSAIDs), MA (SMD = -0.63, 95% CI [-0.88, -0.37]) and warm acupuncture (WA) (SMD = -1.12, 95% CI [-1.81, -0.43]) were more effective at reducing menstrual pain. Some studies showed that the efficacy of acupuncture was maintained after a short-term follow-up. CONCLUSION: The results of this study suggest that acupuncture might reduce menstrual pain and associated symptoms more effectively compared to no treatment or NSAIDs, and the efficacy could be maintained during a short-term follow-up period. Despite limitations due to the low quality and methodological restrictions of the included studies, acupuncture might be used as an effective and safe treatment for females with primary dysmenorrhea.

Cytokeratin7 expression in histologic and cytologic specimens of cystic neck metastasis from HPV positive squamous cell carcinoma of the tonsil: A case report.

The majority of cystic squamous cell carcinomas (SCCs) of the neck have been shown to be metastatic tumors from tonsillar SCCs associated with high-risk human papillomavirus (HR HPV). Recent studies have demonstrated cytokeratin (CK)7 involvement in the development of HPV positive SCC, but no report has been issued on its simultaneous expression in primary tonsillar and metastatic tumor with cystic change. We present a case of HPV positive tonsillar SCC of a 42-year-old male that initially manifested as a cystic neck mass expressing CK7, CK19, and p16 in primary and metastatic tumors. Immunohistochemical examination revealed diffuse CK19 and p16 expression, and patchy CK7 expression in the solid components of primary and metastatic tumors. However, in cystic components of metastatic tumors the expression of CK7 and CK19 was preserved but p16 expression was absent, which was consistent with immunocytochemical findings of fine-needle aspirates from cystic neck mass. In immunocytochemistry performed on aspirates of a branchial cleft cyst for the comparison of cystic SCC and benign cyst, CK19 staining was positive but CK7 and p16 staining was negative. These results suggest that CK7 immunocytochemistry on aspirated material from cystic neck mass may be a useful adjunct for distinguishing cystic metastasis of tonsillar SCC from branchial cleft cyst, although a larger scale study would be required.

Phosphorylated mTOR Expression Profiles in Human Normal and Carcinoma Tissues.

Mammalian target of rapamycin (mTOR) is a key controller of cell growth and proliferation in normal tissues and solid tumors. In the present study, an immunohistochemical analysis of the expression pattern of phosphorylated mTOR (p-mTOR) was performed in human normal fetal and adult tissues and various carcinoma tissues. p-mTOR expression showed tissue and cell type specificity in normal and cancer tissues. In normal fetal and adult tissues, p-mTOR staining was observed in the intestinal crypt, intrahepatic bile ductule, pancreatic duct, distal nephron of the kidney, umbrella cell of urothelium, mesothelial cell, and choroid plexus. In cancer tissues, p-mTOR expression was higher in adenocarcinoma than in other types of cancers, in metastatic cancer than in primary cancer, and in the forefront of the infiltrating cancer cells. These results suggest that p-mTOR is implicated not only in cell proliferation but also in tubular morphogenesis in normal and cancer tissues. In addition, mTOR activation appears to be associated with cancer cell invasion and migration in solid tumors.

Cytokeratin7 and cytokeratin19 expression in high grade cervical intraepithelial neoplasm and squamous cell carcinoma and their possible association in cervical carcinogenesis.

BACKGROUND: High risk human papillomavirus (HR HPV) infects cells at the squamocolumnar junction (SCJ) of the cervix, causing cancer. Cytokeratin (CK)7 is an SCJ marker, and stains cervical neoplasia. CK19 is a binding partner of CK7 and expressed in cervical cancer. Despite this possible association between CK7/CK19 and cervical cancer, not much is known about the mechanism of CK7/CK19 involvement in HR HPV-mediated cervical carcinogenesis. METHODS: We analyzed the expression pattern of CK7, CK19, and p16 by using immunohistochemistry and HPV infection by in situ hybridization in 25 cases of high grade cervical intraepithelial neoplasia (CIN3) and in 30 cases of squamous cell carcinoma (SCC). RESULTS: CK19, p16, and HPV expression was positive in all CIN3 and SCC cases. CK7 expression was positive in all CIN3 cases and in 20/30 (66%) SCCs. Each protein showed diffuse or patchy staining with topographic distinction. Patchy staining of CK7 and episomal HPV DNA overlapped in the upper layer of CIN3 and central portion of an invasive nest in the SCC, whereas patchy CK19 staining and integrated HPV DNA were usually noted in the lower layer of CIN3 and the periphery of the SCC nest. The p16 staining pattern coincided with that of CK19 in a subset of SCC. CONCLUSION: These results suggest that CK7 may be more related with viral episomal replication and CK19 with viral integration, contributing to viral replication and malignant transformation in HR HPV infected cells. In addition, coordinate CK7/CK19 staining may be used as a valuable marker for predicting physical status of HR HPV and E7 oncoprotein level in cervical tumor.

Glycogen synthase kinase 3ß and cyclin D1 expression in cervical carcinogenesis.

OBJECTIVE: Glycogen synthase kinase 3ß (GSK3ß) is a pluripotent protein kinase involved in the development of cancers through regulation of numerous oncogenic molecules. Cyclin D1, an important regulator of G1 to S phase transition in various cells, is one of target proteins that GSK3ß regulate. Our objective was to assess the expression of GSK3ß and cyclin D1 in cervical neoplasm of different histologic grades and to identify their correlation in cervical carcinogenesis. METHODS: Immunohistochemical analysis of GSK3ß and cyclin D1 was performed in a total of 137 patients with 12 normal, 62 cervical intraepithelial neoplasia (CIN) (31 CIN1 and 31 CIN3) and 63 invasive cancers including 56 squamous cell carcinomas and 7 adenocarcinomas. RESULTS: The expression of GSK3ß increased in parallel with the lesion grade, while that of cyclin D1 decreased with severity of the lesion (P<0.001). There was a significant inverse correlation between GSK3ß and cyclin D1 expression in overall cervical neoplasia (Φ=-0.413, P<0.001). GSK3ß expression was higher in squamous cell carcinoma than in adenocarcinoma (P=0.049). CONCLUSION: These results suggest that the expressional increase in GSK3ß plays a role in cervical carcinogenesis and has inverse correlation with cyclin D1 expression in this process. In addition, GSK3ß expression appears to be associated with the histologic type of cervical cancer, especially squamous cell carcinoma.

Mutational Analysis of Extranodal NK/T-Cell Lymphoma Using Targeted Sequencing with a Comprehensive Cancer Panel.

Extranodal natural killer (NK)/T-cell lymphoma, nasal type (NKTCL), is a malignant disorder of cytotoxic lymphocytes of NK or T cells. It is an aggressive neoplasm with a very poor prognosis. Although extranodal NKTCL reportedly has a strong association with Epstein-Barr virus, the molecular pathogenesis of NKTCL has been unexplored. The recent technological advancements in next-generation sequencing (NGS) have made DNA sequencing cost- and time-effective, with more reliable results. Using the Ion Proton Comprehensive Cancer Panel, we sequenced 409 cancer-related genes to identify somatic mutations in five NKTCL tissue samples. The sequencing analysis detected 25 mutations in 21 genes. Among them, KMT2D, a histone modification-related gene, was the most frequently mutated gene (four of the five cases). This result was consistent with recent NGS studies that have suggested KMT2D as a novel driver gene in NKTCL. Mutations were also found in ARID1A, a chromatin remodeling gene, and TP53, which also recurred in recent NGS studies. We also found mutations in 18 novel candidate genes, with molecular functions that were potentially implicated in cancer development. We suggest that these genes may result in multiple oncogenic events and may be used as potential bio-markers of NKTCL in the future.

Acupuncture for heart failure: A systematic review of clinical studies.

BACKGROUND: Acupuncture has been used for treating heart failure mainly in combination with conventional treatments, but evidence for its effectiveness and safety has not been well established. Our aim was to review randomized controlled trials (RCTs) on acupuncture for heart failure and assess the clinical evidence. METHODS: Electronic databases such as Medline, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL) and certain Chinese & Korean databases were searched until October 2015. The main outcomes assessed were mortality, New York Heart Association (NYHA) function classifications, and acupuncture-related adverse events. The details of acupuncture intervention were also investigated. RESULTS: Among 4107 publications, seven RCTs were included; most of them showed considerable methodological flaws. We could not conduct a meta-analysis because of the heterogeneity of the included studies. In one acute heart failure study, acupuncture shortened intensive care unit (ICU) stay by 2.2days (95% CI 1.26, 3.14) and reduced the risk ratio of re-admission to 0.53 (95% CI 0.28, 0.99). However, mortality was not affected. Hemodynamic parameters also showed improvement. Another study reported an improved left ventricular ejection fraction by 9.95% (95% CI 3.24, 16.66). In five chronic heart failure studies, acupuncture improved exercise capacity, quality of life, hemodynamic parameters, and time domain heart rate variability parameters. Acupuncture decreased NT-pro BNP levels by 292.20 (95% CI -567.36, -17.04). No adverse effects were reported. CONCLUSIONS: The effectiveness of acupuncture as a therapy for heart failure is currently inconclusive. Further large and rigorous clinical trials are needed to establish its clinical utility.

Electroacupuncture to treat gastroesophageal reflux disease: study protocol for a randomized controlled trial.

BACKGROUND: Gastroesophageal reflux disease lowers the quality of life and increases medical costs. Electroacupuncture has been used to ease symptoms and improve gastrointestinal motility in patients with gastroesophageal reflux disease. The main purposes of this study are to evaluate the efficacy and safety of this procedure. METHODS/DESIGN: This is a protocol for a randomized, patient-blinded, assessor-blinded, sham-controlled trial. Sixty participants with symptoms of gastroesophageal reflux disease, who have previously undergone standard treatment, will be recruited from August 2015 at Kyung Hee University Korean Medicine Hospital. The participants will be allocated to either the electroacupuncture (n = 30) or the sham electroacupuncture group (n = 30); the allocation will be concealed from both the participants and the assessors. The EA group will undergo penetrating acupuncture at 18 fixed points and two optional points chosen using the pattern identification for gastroesophageal reflux disease. Electrical stimulation will be applied at some of the acupoints. The sham electroacupuncture group will undergo nonpenetrating acupuncture without electrical stimulation at 18 nonspecific points, each of which will be only 2 cm away from the true acupoints used in the electroacupuncture group. In both groups, the procedure will be performed using the Park device. The treatment will last for 6 weeks (with two sessions each week), and the outcome will be evaluated at baseline, 3 weeks, and 6 weeks. The primary outcome will be the proportion of responders with adequate symptom relief, whereas the secondary outcomes will comprise the results of the Nepean dyspepsia index; the Korean gastrointestinal symptom rating scale; the EQ-5D™; levels of gastrin, motilin, and inflammatory cytokines; the perceived stress scale; the qi-stagnation questionnaire; the patient global impression of change; and the spleen qi deficiency questionnaire. DISCUSSION: The results of this trial will provide information about the efficacy and safety of electroacupuncture in the treatment of gastroesophageal reflux disease symptoms, as well as evidence regarding the use of electroacupuncture to treat gastroesophageal reflux disease in real clinical practice. TRIAL REGISTRATION: Clinical Research Information Service Identifier, KCT0001653 . Registered on 12 October 2015.