Chee-Yin Chai

Antigen-specific cancer immunotherapy and antiangiogenesis have emerged as two attractive strategies for cancer treatment. An innovative approach that combines both mechanisms will likely generate the most potent antitumor effect. We tested this approach using calreticulin (CRT), which has demonstrated the ability to enhance MHC class I presentation and exhibit an antiangiogenic effect. We explored the linkage of CRT to a model tumor antigen, human papilloma virus type-16 (HPV-16) E7, for the development of a DNA vaccine. We found that C57BL/6 mice vaccinated intradermally with CRT/E7 DNA exhibited a dramatic increase in E7-specific CD8+ T cell precursors and an impressive antitumor effect against E7-expressing tumors compared with mice vaccinated with wild-type E7 DNA or CRT DNA. Vaccination of CD4/CD8 double-depleted C57BL/6 mice and immunocompromised (BALB/c nu/nu) mice with CRT/E7 DNA or CRT DNA generated significant reduction of lung tumor nodules compared with wild-type E7 DNA, suggesting that antiangiogenesis may have contributed to the antitumor effect. Examination of microvessel density in lung tumor nodules and an in vivo angiogenesis assay further confirmed the antiangiogenic effect generated by CRT/E7 and CRT. Thus, cancer therapy using CRT linked to a tumor antigen holds promise for treating tumors by combining antigen-specific immunotherapy and antiangiogenesis.

Our objective was to investigate and compare the effects of heat-killed (HK) and live Lactobacillus reuteri GMNL-263 (Lr263) on insulin resistance and its related complications in high-fat diet (HFD)-induced rats. Male Sprague-Dawley rats were fed with a HFD with either HK or live Lr263 for 12 weeks. The increases in the weight gain, serum glucose, insulin, and lipid profiles in the serum and liver observed in the HFD group were significantly reduced after HK or live Lr263 administration. Feeding HK or live Lr263 reversed the decreased number of probiotic bacteria and increased the number of pathogenic bacteria induced by high-fat treatment. The decreased intestinal barrier in the HFD group was markedly reversed by HK or live Lr263 treatments. The elevations of pro-inflammatory associated gene expressions in both adipose and hepatic tissues by high-fat administration were markedly decreased by HK or live Lr263 treatments. The increased macrophage infiltration noticed in adipose tissue after high-fat treatment was effectively suppressed by HK or live Lr263 consumption. The insulin resistance associated gene expressions in both adipose and hepatic tissues, which were downregulated in the HFD group, were markedly enhanced after HK or live Lr263 administration. HK or live Lr263 consumption significantly decreased hepatic lipogenic gene expressions stimulated by high-fat treatment. Administration of HK or live Lr263 significantly reduced hepatic oil red O staining and ameliorated the hepatic steatosis observed in high-fat treated rats. Our data suggested that similar to live Lr263, HK Lr263 exerted significant effects on attenuating obesity-induced metabolic abnormalities by reducing insulin resistance and hepatic steatosis formation.

The interaction between integrins and extracellular matrix proteins play an important role in the regulation of hematopoiesis. Human hematopoietic progenitor cells express very late antigen-4 (VLA-4) and VLA-5, which mediate their interaction with fibronectin by recognizing the connecting segment-1 (CS-1 and RGD motifs, respectively. In this study, we investigated the ex vivo expansion of human umbilical cord blood (UCB) CD34+ cells on synthetic substrates surface-immobilized with peptides containing the CS-1 binding motif (EILDVPST) and the RGD motif (GRGDSPC). These peptides were covalently conjugated to poly(ethylene terephthalate) (PET) film at a surface density of 2.0–2.3 nmol/cm2. UCB CD34+ cells were cultured for 10 days in serum-free medium supplemented with recombinant human thrombopoietin, stem cell factor, flt3-ligand and interleukin 3. The highest cell expansion fold was observed on the CS-1 peptide-modified surface, where total nucleated cells, total colony forming unit, and long-term culture initiating cells were expanded by 589.6±58.6 (mean±s.d.), 76.5±8.8, and 3.2±0.9-fold, respectively, compared to unexpanded cells. All substrates surface-immobilized with peptides, including the control peptides, were more efficient in supporting the expansion of CD34+, CFU-GEMM and LTC-ICs than tissue culture polystyrene surface. Nevertheless, after 10-days of ex vivo expansion from 600 CD34+ cells, only cells cultured on CS-1-immobilized surface yielded positive engraftment, even though the frequency was low. PET surface immobilized with RGD peptide was less efficient than that with CS-1 peptide. Our results suggest that covalently immobilized adhesion peptides can significantly influence the proliferation characteristics of cultured UCB CD34+ cells.

Reprogramming of cancer cells into induced pluripotent stem cells (iPSCs) is a compelling idea for inhibiting oncogenesis, especially through modulation of homeobox proteins in this reprogramming process. We examined the role of various long noncoding RNAs (lncRNAs)-homeobox protein HOXA13 axis on the switching of the oncogenic function of bone morphogenetic protein 7 (BMP7), which is significantly lost in the gastric cancer cell derived iPS-like cells (iPSLCs). BMP7 promoter activation occurred through the corecruitment of HOXA13, mixed-lineage leukemia 1 lysine N-methyltransferase, WD repeat-containing protein 5, and lncRNA HoxA transcript at the distal tip (HOTTIP) to commit the epigenetic changes to the trimethylation of lysine 4 on histone H3 in cancer cells. By contrast, HOXA13 inhibited BMP7 expression in iPSLCs via the corecruitment of HOXA13, enhancer of zeste homolog 2, Jumonji and AT rich interactive domain 2, and lncRNA HoxA transcript antisense RNA (HOTAIR) to various cis-element of the BMP7 promoter. Knockdown experiments demonstrated that HOTTIP contributed positively, but HOTAIR regulated negatively to HOXA13-mediated BMP7 expression in cancer cells and iPSLCs, respectively. These findings indicate that the recruitment of HOXA13-HOTTIP and HOXA13-HOTAIR to different sites in the BMP7 promoter is crucial for the oncogenic fate of human gastric cells. Reprogramming with octamer-binding protein 4 and Jun dimerization protein 2 can inhibit tumorigenesis by switching off BMP7. Stem Cells 2017;35:2115-2128.

Certain domains of bacterial toxins have been shown to facilitate translocation from extracellular and vesicular compartments into the cytoplasm. This feature represents an opportunity to enhance class I presentation of exogenous antigen to CD8(+) T cells. We investigated this notion by creating a novel fusion of the translocation domain (domain II) of Pseudomonas aeruginosa exotoxin A (ETA(dII)) with a model tumor antigen, human papillomavirus type 16 E7, in the context of a DNA vaccine. Our in vitro studies indicated that cells transfected with ETA(dII)/E7 DNA or dendritic cells pulsed with lysates containing ETA(dII)/E7 protein exhibited enhanced MHC class I presentation of E7 antigen. Vaccination of mice with ETA(dII)/E7 DNA generated a dramatic increase in the number of E7-specific CD8(+) T cell precursors ( approximately 30-fold compared with wild-type E7 DNA) and converted a less effective DNA vaccine into one with significant potency against human papillomavirus type 16 E7-expressing murine tumors via a CD8-dependent pathway. These results indicate that fusion of the translocation domain of a bacterial toxin to an antigen may greatly enhance vaccine potency.

Lercanidipine, a calcium channel antagonist, is currently employed in the treatment of essential hypertension and angina pectoris. The purpose of this study was to elucidate the anti-proliferative effect of lercanidipine and to investigate the molecular role of this agent. Both in vitro studies and in a balloon injury rat carotid artery model were employed to study the effect of lercanidipine on smooth muscle cell proliferation. Lercanidipine-inhibited rat vascular smooth muscle cell (VSMC) proliferation and migration in a dose-dependent manner following stimulation of VSMC cultures with 10% fetal bovine serum (FBS) and 20 ng/ml platelet-derived growth factor (PDGF)-BB. FBS- and PDGF-BB-stimulated intracellular Ras, MEK1/2, ERK1/2, proliferative cell nuclear antigen (PCNA), and Akt activations were significantly inhibited by lercanidipine; however, lercanidipine did not affect FBS- and PDGF-BB-induced STAT3 phosphorylation. Lercanidipine also inhibited PDGF-receptor β chain phosphorylation and reactive oxygen species (ROS) production induced by PDGF-BB. Lercanidipine blocked the FBS-inducible progression through the G0/G1 to the S-phase of the cell cycle in synchronized cells. In vivo, 14 days after balloon injury, treatment with 3 and 10 mg/kg lercanidipine resulted in significant inhibition of the neointima/media ratio. Suppression of neointima formation by lercanidipine was dependent on its influence on ERK1/2 phosphorylation. These results demonstrate that lercanidipine can suppress the proliferation of VSMCs via inhibiting cellular ROS, Ras-MEK1/2-ERK1/2, and PI3K-Akt pathways, and suggesting that it may have therapeutic relevance in the prevention of human restenosis.

To evaluate the expression and prognostic value of two autophagy-related (Atg) proteins, Beclin-1 and Atg5, in human oral squamous cell carcinoma (OSCC) and to correlate findings with clinical outcomes.Immunohistochemistry for Beclin-1 and Atg5 was assessed in tumor specimens from 90 patients with OSCC. Immunopositivity was semi-quantitatively scored and receiver-operating characteristic curve analysis was used to determine the cut-off positivity score.55 (61.1%) and 52 (57.8%) cases showed positive Beclin-1 and Atg5 staining, respectively. 40 tumors (44.4%) were positive for both Beclin-1 and Atg5 expression and 23 cases (25.6%) showed absence of both proteins. Beclin-1 expression significantly correlated with tumor grade (p=0.008) and lymph node metastasis (p=0.009). The expression of Atg5 was associated with tumor grade (p=0.016), advanced clinical stage (p<0.001), large tumor size (p=0.002), and lymph node metastasis (p<0.001). A significant difference in 3-year OS (p=0.050) and TTR (p=0.049) between the patients with Beclin-1 expression and those not showing Beclin-1 expression was found whereas the difference did not reach a statistical significance for Atg5 expression. 3-year OS and TTR differed significantly between patients with dual expression and those with double-negative expression (p=0.022 and p=0.026, respectively).Dual expression of tumor Beclin-1 and Atg5 expression may be an adverse prognostic indicator for OSCC.

In Taiwan, the average prevalence of congenital heart disease (CHD) is 13.08/1000 live births. Most children with CHD die before the age of 5 years; therefore, identifying treatment methods to extend the life of CHD patients is an important issue in clinical practice. The objective of this study is to evaluate the roles of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), inducible nitric oxide synthase (iNOS), endothelin-1 (ET-1), and CD34 in CHD autopsy cases in comparison with autopsy cases without CHD. The study included 19 autopsy cases, which were divided into the following four groups: acyanotic CHD (n = 11), cyanotic CHD (n = 3), CHD associated with chromosomal abnormalities (n = 3), and complex CHD (n = 2). Heart specimens obtained from 10 autopsy cases without CHD were included as controls. Our results indicated that high percentages of HIF-1α (100%), VEGF (89.5%), iNOS (78.9%), and ET-1 (84.2%) expressions were observed in CHD autopsy cases and this was found to be significant. HIF-1α induced by hypoxia could play a potential role in relating downstream gene expressions in CHD patients. Upregulation of VEGF by HIF-1α could play an important role in triggering angiogenesis to protect myocardial cell survival in a hypoxic microenvironment. Therefore, HIF-1α could be a significant prognosis marker in CHD and be a prospective candidate in the development of target therapy in cardiovascular diseases.

Recently, Flt3 (Fms-like tyrosine kinase 3)-ligand has been identified as an important cytokine for the generation of professional antigen-presenting cells (APCs), particularly dendritic cells (DCs). A recombinant chimera of the extracellular domain of Flt3-ligand (FL) linked to a model antigen may potentially target the antigen to DCs and their precursor cells. Using human papillomavirus-16 E7 as a model antigen, we evaluated the effect of linkage to FL on the potency of antigen-specific immunity generated by naked DNA vaccines administered intradermally via gene gun. We found that vaccines containing chimeric FL-E7 fusion genes significantly increased the frequency of E7-specific CD8+ T cells relative to vaccines containing the wild-type E7 gene. In vitro studies indicated that cells transfected with FL-E7 DNA presented E7 antigen through the MHC class I pathway more efficiently than wild-type E7 DNA. Furthermore, bone marrow-derived DCs pulsed with cell lysates containing FL-E7 fusion protein presented E7 antigen through the MHC class I pathway more efficiently than DCs pulsed with cell lysates containing wild-type E7 protein. More importantly, this fusion converted a less effective vaccine into one with significant potency against established E7-expressing metastatic tumors. The FL-E7 fusion vaccine mainly targeted CD8+ T cells, and antitumor effects were completely CD4 independent. These results indicate that fusion of a gene encoding the extracellular domain of FL to an antigen gene may greatly enhance the potency of DNA vaccines via CD8-dependent pathways.

Colorectal cancer (CRC) is one of the most common causes of cancer-related deaths worldwide. DNA double-strand breaks (DSBs) are deleterious lesions that can lead to chromosomal anomalies, genomic instability and cancer. The histone H2AX plays an important role in response to DNA damage and phosphorylation of H2AX (p-H2AX) is evidence of DSBs. The aim of this study was to evaluate the clinical significance of p-H2AX expression in CRC.p-H2AX expression in CRC tissues was analyzed by immunohistochemistry and correlated with clinicopathological variables using the chi-square test. The prognostic value of p-H2AX for distant metastasis-free survival (DMFS) and overall survival (OS) was evaluated by Kaplan-Meier estimates and the individual prognostic components were analyzed with Cox regression analysis.A high p-H2AX expression in CRC tissues was associated with tumor stage and perineurial invasion. Furthermore, a high p-H2AX expression was associated with poor DMFS and OS. Cox regression analysis also revealed that p-H2AX was an independent predictor of DMFS and OS.A high p-H2AX expression in CRC tissues is associated with a more malignant cancer behavior, as well as poor patient survival. p-H2AX may, therefore, be an independent prognostic predictor for CRC, as well as a potential therapeutic target.

Background: Burn scar pain is considered as neuropathic pain. The anti-inflammation and anti-neuroinflammation effects of adipose-derived stem cells (ASCs) were observed in several studies. We designed a study using a murine model involving the transplantation of autologous ASCs in rats subjected to burn injuries. The aim was to detect the anti-neuroinflammation effect of ASC transplantation and clarify the relationships between ASCs, scar pain, apoptosis and autophagy. Methods: We randomized 24 rats into 4 groups as followings: Group A and B, received saline injections and autologous transplantation of ASCs 4 weeks after sham burn, respectively; Group C and D, received saline injections and autologous transplantation 4 weeks after burn injuries. A designed behavior test was applied for pain evaluation. Skin tissues and dorsal horn of lumbar spinal cords were removed for biochemical analysis. Results: ASC transplantation significantly restored the mechanical threshold reduced by burn injury. It also attenuated local inflammation and central neuroinflammation and ameliorated apoptosis and autophagy in the spinal cord after the burn injury. Conclusion: In a rat model, autologous ASC subcutaneous transplantation in post-burn scars elicited anti-neuroinflammation effects locally and in the spinal cord that might be related to the relief of post-burn neuropathic pain and attenuated cell apoptosis. Thus, ASC transplantation post-burn scars shows the potential promising clinical benefits.

Operative hysteroscopy is a common gynecologic procedure, but it carries the risk of complications. Spontaneous small intestine perforation is rare and fatal, especially in young adults. We present a spontaneous small intestine perforation after operative hysteroscopy with mimicking sign of uterine perforation after operation hysteroscopy.A 30-year-old nulligravida woman underwent Truclear® hysteroscopic polypectomy in the morning in LMD. She suffered from upper abdominal pain in the afternoon. Subsequently, progressive abdominal distention and imminent shock occurred the next morning. Initially, it was supposed to be a case of uterine rupture with internal bleeding. She was transferred to the emergency department of our hospital. Complete biochemistry data and abdominal CT were performed. The CT revealed pneumoperitoneum and ascites. Emergent laparoscopy was arranged. The abdominal cavity was full of intestinal fluid and the myomatous uterus was intact. The surgeon performed a laparotomy, two sites of spontaneous perforation of the small intestine were detected. The patient underwent laparotomic segmental resection and anastomosis and was discharged 14 days after surgery without incident.The risk of uterine perforation during hysteroscopy is up to 1.6%. The use of non-thermal intrauterine morcellator device (Truclear®) has been shown to significantly reduce the risk of perforation and thermal injury. As this case highlights, we suspected the possibility of uterine perforation immediately after hysteroscopic surgery. However, it happened to be rare spontaneous perforation of small bowel. The patient recovered well after timely transfer and management. Hysteroscopy is a very common procedure in gynecologic clinics, but even relatively safe intrauterine morcellator devices carry risk of complications. As a healthcare provider, we should beware of any comorbidity, for sometimes it would be catastrophic.

KMUP-1 (7-[2-[4-(2-chlorobenzene)piperazinyl]ethyl]-1,3-dimethylxanthine) has been reported to cause hepatic fat loss. However, the action mechanisms of KMUP-1 in obesity-induced steatohepatitis remains unclear. This study elucidated the steatohepatitis via matrix metallopeptidase 9 (MMP-9) and tumor necrosis factor α (TNFα), and related lipolysis via hormone sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) by KMUP-1. KMUP-1 on steatohepatitis-associated HSL/p-HSL/ATGL/MMP-9/TNFα/interleukin-10 (IL-10) and infiltration of M1/M2 macrophages in obese mice were examined. KMUP-1 was administered by oral gavage from weeks 1-14 in high-fat diet (HFD)-supplemented C57BL/6J male mice (protection group) and from weeks 8-14, for 6 weeks, in HFD-induced obese mice (treatment group). Immunohistochemistry (IHC) and hematoxylin and eosin (H&amp;E) staining of tissues, oil globules number and size, infiltration and switching of M1/M2 macrophages were measured to determine the effects on livers. IL-10 and MMP-9 proteins were explored to determine the effects of KMUP-1 on M1/M2 macrophage polarization in HFD-induced steatohepatitis. Long-term administration of KMUP-1 reversed HFD-fed mice increased in body weight, sGOT/sGPT, triglyceride (TG) and glucose. Additionally, KMUP-1 decreased MMP-9 and reactive oxygen species (ROS), and increased HSL/p-HSL and IL-10 in HFD mice livers. In conclusion, KMUP-1, a phosphodiesterase inhibitor (PDEI), was shown to reduce lipid accumulation in liver tissues, suggesting that it could be able to prevent or treat steatohepatitis induced by HFD.

C-Src activity is regulated by tyrosine phosphorylation at two distinct sites, Tyr416 and Tyr527, with opposite effects. However, the clinical roles of these sites in human cancers are not well defined. This study aims to determine whether the alterations and crosstalk of these two sites may contribute to hepatocellular carcinoma (HCC). Specimens from 85 patients who had undergone curative hepatectomy were collected for this study. The patterns of p-Tyr416-Src and p-Tyr527-Src, as well as the non-phosphorylated status for each site, were determined using immunohistochemistry and statistically correlated with clinicopathological characteristics and overall survival rate. The active state of c-Src, p-Tyr416-c-Src, was positively correlated with tumour grade ( P = 0.062) but inversely correlated with vascular invasion ( P = 0.071). Its non-phosphorylated status, non-p-Tyr416-c-Src, was positively correlated with tumour stage and grade ( P = 0.041 and 0.020). The inactive state of c-Src, p-Tyr527-c-Src, was decreased in male patients but increased HCV-infected patients ( P = 0.044 and 0.033). The Kaplan-Meier survival curve further showed that increased p-Tyr416-c-Src and decreased non-p-Tyr527-c-Src expression were associated with a poor patient survival rate ( P = 0.004 and 0.025). Interestingly, the expression of non-p-Tyr416-c-Src was positively correlated with that of p-Tyr527-c-Src in the HCC lesions ( P = 0.040). In addition, the patients with concomitantly low p-Tyr416-c-Src and non-p-Tyr527-c-Src expression had a prolonged overall survival rate ( P = 0.030). A multivariable COX regression model showed that p-Tyr416-c-Src expression was an effective predictor for patient survival in HCC [OR = 3.78, 95%CI = 1.46–9.76; P = 0.006]. Our results suggest that the active state of c-Src, p-Tyr416-c-Src, may serve as an independent prognostic marker of patient survival in HCC. Relative levels of other phosphorylated or non-phosphorylated c-Src kinases may also present different statuses during HCC development and require further investigation.

C-Src activity is regulated by tyrosine phosphorylation at two distinct sites, Tyr416 and Tyr527, with opposite effects. However, the clinical roles of these sites in human cancers are not well defined. This study aims to determine whether the alterations and crosstalk of these two sites may contribute to hepatocellular carcinoma (HCC). Specimens from 85 patients who had undergone curative hepatectomy were collected for this study. The patterns of p-Tyr416-Src and p-Tyr527-Src, as well as the non-phosphorylated status for each site, were determined using immunohistochemistry and statistically correlated with clinicopathological characteristics and overall survival rate. The active state of c-Src, p-Tyr416-c-Src, was positively correlated with tumour grade (P=0.062) but inversely correlated with vascular invasion (P=0.071). Its non-phosphorylated status, non-p-Tyr416-c-Src, was positively correlated with tumour stage and grade (P= 0.041 and 0.020). The inactive state of c-Src, p-Tyr527-c-Src, was decreased in male patients but increased HCV-infected patients (P=0.044 and 0.033). The Kaplan-Meier survival curve further showed that increased p-Tyr416-c-Src and decreased non-p-Tyr527-c-Src expression were associated with a poor patient survival rate (P=0.004 and 0.025). Interestingly, the expression of non-p-Tyr416-c-Src was positively correlated with that of p-Tyr527-c-Src in the HCC lesions (P=0.040). In addition, the patients with concomitantly low p-Tyr416-c-Src and non-p-Tyr527-c-Src expression had a prolonged overall survival rate (P=0.030). A multivariable COX regression model showed that p-Tyr416-c-Src expression was an effective predictor for patient survival in HCC [OR =3.78, 95% CI =1.46-9.76; P=0.006]. Our results suggest that the active state of c-Src, p-Tyr416-c-Src, may serve as an independent prognostic marker of patient survival in HCC. Relative levels of other phosphorylated or non-phosphorylated c-Src kinases may also present different statuses during HCC development and require further investigation.

p53 plays an important role in maintaining genomic stability and regulating the cell cycle. However, the accumulation of p53 protein has been reported to be involved in the carcinogenesis, progression, and metastasis of many types of human cancer. This study evaluates the clinical significance of p53 expression in upper tract urothelial carcinoma.One-hundred and twelve cases of upper tract urothelial carcinoma were included in this study. p53 expression was evaluated by immunohistochemistry and the association of p53 expression with clinicopathological variables was analyzed.p53 expression was significantly correlated with patients who were undergoing hemodialysis (p=0.005) and had increased serum creatinine levels (p=0.001). High p53 expression was associated with poor progression-free (p=0.025) and cancer-specific survival (p=0.021), Cox regression analysis also revealed that p53 was an independent predictor of poor progression-free (hazard ratio=3.74, p=0.025) and cancer-specific (hazard ratio=5.87, p=0.030) survival.Our findings indicate that p53 expression is a potential biomarker for predicting patient survival. Further study is necessary to investigate the role of p53 in the carcinogenesis of upper tract urothelial carcinoma.

Colorectal cancer (CRC) of the clinical tumor stage T4b (cT4b) refers to advanced tumors with direct invasion of adjacent structures and the tumors are considered unresectable. Despite advancements in aggressive surgery and combination chemotherapy, the prognosis of cT4b CRC remains poor. Optimizing the therapeutic sequence administered to patients with cT4b CRC to improve clinical outcomes is crucial. In the present study, patients with unresectable cT4b and nodal stage N1‑2 CRC were investigated at a single institution. A total of 20 consecutive patients were treated with pre‑operative concurrent chemoradiation by using 5‑fluorouracil/leucovorin/oxaliplatin (FOLFOX) since February 2015 and were regularly followed up until March 2020. Due to their poor response to concurrent chemoradiation (CCRT) with FOLFOX, the chemotherapy regimen was changed to irinotecan plus 5‑fluorouracil/leucovorin (FOLFIRI) as the second‑line neoadjuvant treatment. Genetic alterations, such as microsatellite instability (MSI), were documented, and the expression levels of excision repair cross‑complementing group 1 (ERCC1) and ERCC2 were examined. Of the 20&nbsp;patients, the tumors of 14&nbsp;patients (70%) became resectable after FOLFIRI administration. The median duration between the last date of radiotherapy and surgery was 32.7&nbsp;weeks (range, 10.1‑59.3&nbsp;weeks). Of note, 4 of the 14&nbsp;patients with resectable tumors (28.6%) achieved a pathologic complete response. The median overall survival and progression‑free survival were 27.5&nbsp;months (range, 12‑39&nbsp;months) and 27.5&nbsp;months (range, 8‑39&nbsp;months), respectively. The cancerous specimens of all of the patients (100%) exhibited ERCC2 overexpression and 18 specimens (90%) had ERCC1 overexpression. Only one tumor (5%) exhibited high MSI. The present study indicated that ERCC overexpression associated with the poor response of FOLFOX‑based CCRT and FOLFIRI after FOLFOX‑based CCRT failure may have a potential role in conversion to resectable tumors by neoadjuvant treatment in cT4b CRC. However, a further prospective study with more patients is required to improve the precision of the conclusions.

Vulvovaginal laxity, atrophic vaginitis, and orgasmic dysfunction are not only aesthetic but also sexual problems. Autologous fat grafting (AFG) facilitates tissue rejuvenation through the effects of adipose-derived stem cells; the fat grafts serve as soft-tissue filler. However, few studies have reported the clinical outcomes of patients undergoing vulvovaginal AFG.The aim of this study was to describe a new technique, micro-autologous fat transplantation (MAFT), for AFG in the vulvovaginal area. Posttreatment histologic changes in the vaginal canal that imply improved sexual function were assessed.This retrospective study enrolled females who underwent vulvovaginal AFG performed through MAFT between June 2017 and 2020. Assessments were based on the Female Sexual Function Index (FSFI) questionnaire and on histologic and immunohistochemical staining.In total, 20 female patients (mean age, 38.1 years) were included. On average, 21.9 mL of fat was injected into the vagina and 20.8 mL in the vulva and mons pubis area. Six months afterwards, the patients' mean total FSFI score (68.6) was significantly higher than that at baseline (43.8; P < .001). Histologic and immunohistochemical staining of vaginal tissues revealed substantially increased levels of neocollagenesis, neoangiogenesis, and estrogen receptors. By contrast, the level of protein gene product 9.5, which is associated with neuropathic pain, was considerably lower after AFG.AFG performed through MAFT in the vulvovaginal area may help manage sexual function-related problems in females. In addition, this technique improves aesthetics, restores tissue volume, alleviates dyspareunia with lubrication, and reduces scar tissue pain.

Objectif: Evaluer la probabilite de carcinome nasopharynge (CNP) chez les jeunes adultes qui semblent souffrir d'une otite moyenne sereuse (OMS) Devis et localisation: Nous avons revu les caracteristiques cliniques de 87 adultes souffrant d'OMS mais qui ne presentaient aucun autre signe ou symptome suggerant un CNP s'etant presentes au Departement d'ORL du Kaohsiung Medical University Hospital entre janvier 2003 et decembre 2004. Une biopsie a ete prise de routine dans le nasopharynx. Resultats: Cinq de ces patients presentaient un CNP (4 carcinomes non-keratinisant et un carcinome epidermoide). L'otite sereuse a ete attribuee a une IVRS chez 20 patients (23%), a une sinusite chronique chez 15 (17.3%), a une rhinite allergique chez 16 patients (18.4%), au carcinome chez 5 patients (5.7%), a des etiologies variees chez 11 patients (12.6%) et a aucune cause evidente chez les 20 derniers patients (23%). L'incidence de CNP chez les adultes souffrant d'OMS mais ne presentant aucun autre signe ou symptome suggerant un CNP etait de 5.7% (5 sur 87). Ces chiffres sont un peu plus haut que certains autres rapports parce que le CNP a une prevalence elevee a Taiwan. Nous recommandons donc fortement la prise d'une biopsie dans le nasopharynx des patients qui presentent une otite sereuse et chez qui on suspecte un cancer du nasopharynx. Conclusions: Nous concluons que les adultes taiwannais qui presentent seulement une otite moyenne avec effusion dont la cause n'est pas claire devraient etre examines et biopsies pour eliminer un CNP.

Nuchal-type fibroma (NTF) is a rare, benign subcutaneous tumor that usually arises from the posterior neck. NTF is histologically characterised by dense collagen bundles and sparse fibroblasts. Only four trauma-related cases have been previously published. Herein, we present a case of extra NTF with histopathology, and six palanquin porters by using snowball sampling technique in ethnographic field research. A palanquin is a type of human-powered transport carried upon the shoulders mostly seen in religious processions. All individuals (mean age, 26.8 years) displayed similar shoulder masses measuring up to 12 cm in the greatest dimensions. They averaged approximately 8.1 years of palanquin-carrying work each. We believe that long-term, heavy shoulder weight bearing of palanquins in religious dance performances may attribute to the incidence of extra NTF. This study reviews all literature of trauma-associated NTF through PubMed database, and highlights the association between repetitive blunt trauma and the development of NTF.

Darier's disease, also known as keratosis follicularis, is an uncommon autosomal dominant disorder that may also occur as a sporadic mutation. It is characterized by multiple eruptions of hyperkeratotic or crusted papules at seborrheic areas with histologic acantholysis and dyskeratosis. It usually begins in the first or second decade of life and is equally prevalent in men and women. Darier's disease is caused by mutations in the ATP2A2 gene, which maps to chromosome 12q23-q24.1 and encodes the sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA2). The co-occurrence of various neurologic and psychiatric diseases with Darier's disease has been reported, including mood disorders, epilepsy, mental retardation, slowly progressive encephalopathy, and schizophrenia. Linkage studies using the association between these disorders and Darier's disease to determine the gene locus of these psychiatric disorders inferred the presence of a bipolar susceptibility gene on chromosome 12q23-q24.1 in the region of the Darier's disease gene (DAR). We report a case of Darier's disease of more than 40 years' duration and bipolar I disorder of 30 years' duration in a 52-year-old man, and provide a brief review of the literature.

Leukemoid reaction is defined as a reactive leukocytosis in response to infection, inflammation, or therapeutic agents such as growth factors and malignancy. We report a case of leukemoid reaction resulting from granulocyte colony‐stimulating factor producing urothelial carcinoma of the renal pelvis as evidenced on immunohistochemical analysis.

Osseous hemangioma is a benign neoplasm, rarely located in the ribs. A 56-year-old female patient without specific complaint had a large extrapleural lesion on chest posteroanterior radiograph. Expansile destruction of left seventh rib and relatively fine trabeculation were noticed in the mass from plain roentgenogram and computed tomography (CT). Contrast enhancement in noncalcified component of the lesion was revealed. Pleural effusion, lung parenchymal or mediastinal abnormality were not identified. Resection of the lesion with part of the originating rib was carried out. The pathologic diagnosis was cavernous hemangioma. We present a case with a large rib hemangioma which often leads to difficulty in radiologically differential diagnosis with other common malignant rib tumors. We also review the literature about hemangioma and malignant neoplasms of the ribs.

This study revealed that arsenic regulates SLC25A12, PSME3, vinculin, QR and STIP1 expressions through activation of the ERK-signaling pathway.

The human liver consists of three types of liver cells: mature hepatocytes, cholangiocytes, and bipolar adult hepatic stem/progenitor cells (HPC). These three types of cell are commonly regarded as the primary targets of malignant transformation in the liver, if exposed to carcinogens in vivo or in vitro. Activation and proliferation of hepatic progenitor cells have been reported in precancerous conditions, such as chronic inflammation (hepatitis B/hepatitis C, alcoholic hepatitis and steatohepatitis). An origin of hepatocellular carcinoma (HCC) from hepatic progenitor cells is currently inferred from the fact that many tumors contain a mixture of mature cells and cells phenotypically similar to hepatic progenitor cells. In our series, there were 42 patients (31 males, 11 females, aged 23–80 years old) with HCC, who accepted liver resection, yielding specimens sufficient for pathological studies. Immunohistochemical studies were made with human monoclonal antibodies against OV-6, CD133, CK-19, CD44, AFP for investigating the HPC. HPC grading was higher in HCC patients with hepatitis B or hepatitis C and lower in those with non-B or non-C hepatitis. As regards the survival of HCC patients based on the grading of cancer stem cells (CSC) within the tumor, the group of Grade 0 showed a more favorable survival rate than that of Grade 1–3. The 1-, 3-, and 5-year survival rates of Grade 0 and Grade 1–3 were 92%, 76%, and 69%, and 63%, 50%, and 50%, respectively (p = 0.073). These liver CSC would be more resistant to chemotherapeutic agents than tumor cells with limited proliferative potential. In conclusion, we strongly believe that the contributions of HPC warrant research in patients with HCC. Without determining the characteristics of CSC, it is impossible to propose new treatment strategies.

Chronic inflammation and cancer stem cells are known risk factors for tumorigenesis. The aetiology of hepatocellular carcinoma (HCC) involves a multistep pathological process that is characterised by chronic inflammation and hepatocyte damage, but the correlation between HCC, inflammation and cancer stem cells remains unclear. In this study, we examined the role of hepatic progenitor cells in a mouse model of chemical-induced hepatocarcinogenesis to elucidate the relationship between inflammation, malignant transformation and cancer stem cells. We used diethylnitrosamine (DEN) to induce liver tumour and scored for H&E and reticulin staining. We also scored for immunohistochemistry staining for OV-6 expression and analysed the statistical correlation between them. DEN progressively induced inflammation at week 7 (40%, 2/5); week 27 (75%, 6/8); week 33 (62.5%, 5/8); and week 50 (100%, 12/12). DEN progressively induced malignant transformation at week 7 (0%, 0/5); week 27 (87.5%, 7/8); week 33 (100%, 8/8); and week 50 (100%, 12/12). The obtained data showed that DEN progressively induced high-levels of OV-6 expression at week 7 (20%, 1/5); week 27 (37.5%, 3/8); week 33 (50%, 4/8); and week 50 (100%, 12/12). DEN-induced inflammation, malignant transformation and high-level OV-6 expression in hamster liver, as shown above, as well as applying Spearman’s correlation to the data showed that the expression of OV-6 was significantly correlated to inflammation (p = 0.001) and malignant transformation (p < 0.001). There was a significant correlation between the number of cancer stem cells, inflammation and malignant transformation in a DEN-induced model of hepatic carcinogenesis in the hamster.

Glioblastoma multiforme (GBM) is one of the most deadly and recalcitrant illnesses of the neurocentral nervous system in humans. MicroRNAs (miRNAs) are a class of noncoding RNAs that play important roles in the regulation of gene expression and biological processes, including radiosensitivity. In this study, we demonstrated the relationship between miR-3059-3p and radiation in GBM.Radioresistant (RR) cells were obtained by exposing GBM8401 cells to 80 Gy radiation in 20 weekly 4 Gy fractions. miR-3059-3p mRNA and DNA replication helicase/nuclease 2 (DNA2) protein expressions were detected using real-time polymerase chain reaction and immunoblotting. Using flow cytometry, colony formation and apoptosis were identified using miR-3059-3p mimic, miR-3059-3p inhibitor, DNA2 siRNA, and DNA2 plasmid. Immunoblotting was used to detect DNA repair proteins.Low levels of miR-3059-3p and high levels of DNA2 were observed in RR cells. Colony formation and apoptosis assays revealed that miR-3059-3p targeted DNA2 to regulate radioresistance. Immunoblotting revealed that miR-3059-3p regulated the homologous recombination (HR) pathway (Rad51 and Rad52) but not the nonhomologous end joining pathway (ku70 and ku80).Downregulation of DNA2 via miR-3059-3p enhanced the radiosensitivity of GBM cells through the inhibition of the HR pathway.

Neuroendocrine neoplasm (NEN) is a common gastrointestinal (GI) tract tumor divided into the neuroendocrine tumor (NET) and neuroendocrine carcinoma (NEC) according to mitosis and Ki-67 index. However, the objective discordance between interobserver may cause unsuitable diagnosis and misleading treatment. Nowadays, aberrant glycosylation of glycoconjugates inducing further populations of elongated complex oligosaccharide covalent attached to glycoconjugates anchored in the cell membrane by neo-synthesis of cancer-associated alteration of carbohydrate determinants were observed during cancer development. This study aimed to demonstrate the wax physisorption kinetics coupled with Fourier transform infrared (WPK-FTIR) imaging between NET and NEC in the rectum, colon, and stomach by utilizing two wax reagents (beeswax and paraplast) as glycan adsorbents for physical binding glycans of glycoconjugates based on dipole-induced dipole interaction. Results showed greater physisorption with beeswax than that of paraplast, suggesting highly populated elongated glycans of glycoconjugates adhering onto the tumor surfaces of NETs than that of adjacent benign mucosa in the rectum and colon. Besides, the WPK results of gastric NEN tissue sections showed a higher infrared absorbance ratio of beeswax-remnant to paraplast-remnant remains onto the tissue sections referring to a higher population of elongated glycans in gastric NET as compared with that of gastric NEC. Based on our findings, different anatomical locations could share similar phenomena with minor variance. In conclusion, WPK-FTIR imaging may have the potential to be employed as an alternative diagnostic method in GI NENs in the future.

The pathophysiology of nasal polyps remains unclear, but recent work suggests that many cytokines are produced in nasal polyps (NPs) and that they may play various important roles in the pathogenesis of NPs. Transforming growth factor-beta 1 (TGF-beta 1), secreted by many inflammatory cells, is a potent inducer of myofibroblasts. Myofibroblasts express alpha-smooth muscle actin (alpha-SMA) and a source of extracellular matrix (ECM). In this study, we investigated a potential link between inflammation and the growth process in human NPs. Sixteen patients who were affected by NPs and who had undergone functional endoscopic sinus surgery were included in this study. Nasal mucosa of inferior turbinate (NM) of 10 patients who had received rhinoplasty or turbinectomy for other disease was used as the control. alpha-SMA and TGF-beta 1 were detected using immunohistochemistry and the number of labeled cells were counted (alpha-SMA and TGF-beta 1 indices). The expression of alpha-SMA and TGF-beta 1 indices found in NPs and NM was compared using Student's t-test. In our study, alpha-SMA and TGF-beta 1 indices were found to be significantly higher in nasal polyps than in nasal mucosa. TGF-beta 1 produced by inflammatory cells can influence the development of myofibroblasts which in turn can induce extracellular matrix accumulation and, therefore, TGF-beta 1 plays a important role in the formation of nasal polyps.

Sildenafil, an oral phosphodiesterase Type 5 inhibitor, has vasodilatory effects through a cGMP-dependent mechanism. We previously showed that aortic banding could result in left ventricular overloading and pulmonary hypertension (PH). In this study, we investigated whether early administration of sildenafil, either immediately after or 2 weeks after aortic banding, could ameliorate the development of PH and alter gene expression of endothelin (ET)-1 and endothelial nitric oxide synthase (eNOS), and alter the levels of cGMP in rats undergoing an ascending aortic banding. Rats (n = 32) were divided into sham-operated and banding groups with or without treatment. The banded rats were further divided into three groups: (i) receiving saline on Days 1-28 (AOB28; n = 8), (ii) receiving saline on Days 1-14 followed by treatment with 50 mg/kg/day sildenafil on Days 15-28 (AOB28/Sil(15-28); n = 8), and (iii) receiving 50 mg/kg/day sildenafil on days 1-28 (AOB28/Sil(1-28); n = 8). The sham-operated rats were administrated saline on Days 1-28 (n = 8). Four weeks after banding, there was a significant development of PH with pulmonary vascular remodeling. Although both sildenafil-treatment groups had significant increases in cGMP and had reductions in the thickening in the medial layer of pulmonary arteriole, notable attenuation of PH occurred only in the AOB28/Sil(1-28) group. PreproET-1 and eNOS messenger RNA (mRNA) expressions were measured by competitive reverse transcription polymerase chain reaction, and eNOS protein was determined by Western blotting. Sildenafil did not alter the elevated ET-1 or preproET-1 mRNA in banded rats. Interestingly, pulmonary eNOS increased in the AOB28/Sil(1-28) group. In conclusion, early treatment with sildenafil inhibited the rise in pulmonary arterial pressure and pulmonary vascular remodeling in PH secondary to heart failure, and cGMP, but not ET-1, might be involved. Clinically, early repeated administration of sildenafil may offer an alternative in protecting against PH in heart failure.

The concurrent occurrence of thymoma and diffuse large B-cell lymphoma in the thymus has not been previously reported. We describe a 74-year-old man who presented with general weakness, neck lymphadenopathy, night sweats, and body weight loss. A right anterior mediastinal mass was found on computed tomography of the chest. The immunohistochemical stains AE1/AE3, CD20, CD3, and MUM-1 confirmed the different components of the mediastinal tumor. A heavy-chain gene clonality assay and light-chain gene clonality assay confirmed the B-cell clonality of the mediastinal tumor and neck lymph node. The patient had received a complete course of chemotherapy, and the result of positron emission tomography–computed tomography showed complete remission. The pathologic report of this mass revealed composite type A thymoma and diffuse large B-cell lymphoma. If concurrent or composite thymoma and lymphoma are suspected, a thorough examination of the thymoma with a combination of ancillary studies is recommended to rule out the possibility of concurrent lymphoma.

We report our 10-year experience of managing adrenal tumors at Kaohsiung Medical University Hospital (KMUH) between January 1992 and January 2002. In total, 53 patients with adrenal tumors were analyzed, including 19 men (mean age +/- standard deviation, SD, 41.8 +/- 12.9 yr; range, 24-66 yr) and 34 women (mean age +/- SD, 42.3 +/- 12.4 yr; range, 19-74 yr), with an overall mean age +/- SD of 42.6 +/- 12.5 years. All 53 adrenal tumors were confirmed by surgery and pathology. In our series, 41 (77.4%) tumors were functional, of which 39 (95%) were benign; 12 (22.6%) tumors were nonfunctional, of which two (16.7%) were malignant. Overall, women were more common than men in our series, especially in Cushing's syndrome and primary aldosteronism (female:male ratio, 4 and 1.9, respectively). Of the 41 functional adrenal tumors, 20 were primary aldosteronism, 10 were Cushing's syndrome, 10 were pheochromocytoma, and one was an androgen-producing tumor. Of the 12 nonfunctional adrenal tumors, all of which presented as adrenal incidentalomas, four were cortical adenoma, three were myelolipoma, two were ganglioneuroma, one was an adrenal cyst, one was an adrenocortical carcinoma, and one was a metastatic carcinoma. Overall, 48 patients underwent adrenalectomy, three underwent partial adrenalectomy for small and well-circumscribed tumors, and two were explored. The diagnosis and management of adrenal tumors is discussed and the literature reviewed.

Molecular pathology may play an important role in predicting the tumor prognosis, particularly p53, epidermal growth factor receptor (EGFR), and c-erbB-2. We investigated six variables (age, sex, histopathological grade, p53, EGFR, and c-erbB-2) to identify the role of such factors in predicting the outcome of patients with supratentorial astrocytic tumors. Thirty-seven tumors were studied including 9 well-differentiated astrocytomas (WHO grade 2), 19 anaplastic astrocytomas (WHO grade 3), and 9 glioblastomas multiforme (WHO grade 4). In univariate analysis, no statistical significance was found for the prognostic value of the sex (p = 0.2188), age (p = 0.5530), p53 immunostain (p = 0.2194), and c-erbB-2 immunostain (p = 0.4203). A significant correlation with the prognosis was found with respect to the histopathological grade (p = 0.0049) and EGFR expression (p = 0.0284). In multivariate analysis, the histopathological grade was shown to be significant independent variable (p = 0.0152). In WHO grade 2 and 3 astrocytomas, expression of p53 or EGFR was associated with poorer patient outcome. In glioblastomas, expression of p53 was also associated with poorer prognosis. Our studies suggested that conventional histological assessment of supratentorial astrocytic tumors remains the best guide to prognosis. Although no statistical significance was found between the immunostains and survival in variant grades of astrocytomas, there was a trend between p53 or EGFR proteins expression and the decrease of survival time.

Hyperbaric oxygen (HBO) treatment has been proven to attenuate neuroinflammation in rats. This study aimed to determine the potential mechanism underlying the anti-inflammatory effects of HBO treatment on burn-induced neuroinflammation in rats. Thirty-six adult male Sprague&amp;ndash;Dawley (SD) rats were randomly assigned to the following six groups (n = 6 per group): (1) sham burn with sham HBO treatment, (2) sham burn with HBO treatment, (3) burn with 1-week sham HBO treatment, (4) burn with 2-week sham HBO treatment, (5) burn with 1-week HBO treatment, and (6) burn with 2-week HBO treatment. SD rats that received third-degree burn injury were used as a full-thickness burn injury model. Subsequently, we analyzed the expression of proteins involved in the galectin-3 (Gal-3)-dependent Toll-like receptor-4 (TLR-4) pathway through enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC) analysis, and Western blotting, and a behavior test was also conducted. The behavior test revealed that HBO treatment significantly suppressed mechanical hypersensitivity in the burn with HBO treatment group compared with the burn with sham HBO treatment group (p &amp;lt; 0.05). ELISA results showed that tumor necrosis factor alpha (TNF-&amp;alpha;) and interleukin 1 beta (IL-1&amp;beta;) levels in the dorsal horn of the spinal cord and the skin were significantly decreased in the burn with HBO treatment group compared with the burn with sham HBO treatment group (p &amp;lt; 0.05). Western blotting results demonstrated that HBO treatment significantly reduced the expression of Gal-3 and TLR-4 in the dorsal horn of the spinal cord in the burn with HBO treatment group compared with the burn with sham HBO treatment group (p &amp;lt; 0.05). IHC analysis results showed that the expression of Gal-3, TLR-4, CD68, and CD45 in the dorsal horn of the spinal cord was significantly lower in the burn with HBO treatment group than in the burn with sham HBO treatment group (p &amp;lt; 0.05), and the expression of CD68 and macrophage migration inhibitory factor (MIF) in the right hind paw skin was significantly lower. The expression of vimentin and fibroblast growth factor (FGF) in the right hind paw skin was significantly higher after HBO treatment (p &amp;lt; 0.05). This study proved that early HBO treatment relieves neuropathic pain, inhibits the Gal-3-dependent TLR-4 pathway, and suppresses microglia/macrophage activation in a rat model.

Light-emitting diodes (LEDs), particularly in the blue waveform range, are regarded as a major source of circadian rhythm dysregulation. A circadian rhythm dysregulation induced by blue LEDs is associated with non-alcoholic fatty liver disease (NAFLD). Hepatocellular accumulation of lipids is a key event in the early stages of NAFLD. Kupffer cells (KCs) have been reported to be lost in the early onset of NAFLD followed by an inflammatory reaction that alters the liver response to lipid overload. This study focused on the detection of the initial stages (subpathological stages) of LED light-triggered NAFLD. Mice were exposed to either blue or white LED irradiation for 44 weeks. Synchrotron radiation-based Fourier-transform infrared microspectroscopy (SR-FTIRM) and wax physisorption kinetic-Fourier transform infrared (WPK-FTIR) imaging were used to evaluate the ratio of lipid to protein and the glycosylation of glycoprotein, respectively. Immunohistopathological studies on KCs and circadian-related proteins were performed. Although liver biopsy showed normal pathology, an SR-FTIRM study revealed a high hepatic lipid-to-protein ratio after receiving LED illumination. The results of WPK-FTIR demonstrated that a high inflammation index was found in the high irradiance of the blue LED illumnation group. These groups showed a decrease in KC number and an increase in Bmal1 and Reverbα circadian protein expression. These findings provide explanations for the reduction of KCs without subsequent inflammation. A significant reduction of Per2 and Cry1 expression is correlated with the findings of WPK-FTIR imaging. WPK-FTIR is a sensitive method for detecting initiative stages of NAFLD induced by long-term blue LED illumination.

The HER-2/neu proto-oncogene amplification or oncoprotein overexpression is an important prognostic factor and a predictive factor for resistance to endocrine therapy and adjuvant chemotherapy in breast cancers. Moreover, it is an entry criterion in the assessment of patients for whom Herceptin (Trastuzumab) treatment is considered. The overexpression rate of HER-2/neu oncoprotein has been identified in 10% to 40% of human breast cancers. In Taiwan, a higher grade of pathobiologic characteristics of familial breast cancer was also noted than that found in the non-familial group. It is worthwhile to evaluate whether the overexpression is more frequent in familial breast cancers. Fifty-six familial and 111 non-familial breast cancers were studied between 1990 and 1999 to assess both the overexpression of HER-2/neu oncoprotein immunohistochemically and the correlation with the histological type, grade and stage of breast carcinoma. The overexpression rate is higher in the familial breast cancer group (50.0%) when compared with non-familial breast cancer group (36.9%), which did not prove to be statistically significant (P = 0.1068). However, when the infiltrating ductal carcinomas of both groups are compared, it is statistically significant (52.3% vs. 33.7%, P = 0.0429). Overexpression correlated with node status and histological grade of infiltrating ductal carcinomas in non-familial and overall breast cancers. It also correlated with nuclear pleomorphism and mitotic counts, but not tubule formation or tumor size. All 3 cases of Paget's disease revealed overexpression, whereas all 12 cases of mucinous and one case of metaplastic carcinoma and one case of medullary carcinoma were negative. The overexpression rate was higher both in familial and non-familial intraductal carcinomas (57.1% vs. 73.3%, P = 0.4716). No statistical difference was identified between the 2 subsets. A case of infiltrating ductal carcinoma combined with intraductal carcinoma revealed heterogeneous staining in the component of ductal carcinoma in situ, while the invasive component did not. This suggests that overexpression decreases within individual tumors as they evolve from in situ to invasive lesioins. The HER-2/neu may imply a different role in intraductal carcinoma, Paget's disease and invasive duct carcinoma. Although the overexpression rate of HER-2/neu oncoprotein of familial breast cancer was not significantly higher than that of the non-familial group, it is appropriate to evaluate the rate of HER-2/neu overexpression according to the histological type of breast cancers from familial breast cancer and non-familial breast cancer. The prognoses will be needed for future evaluation.

Historically, eosinophilic cystitis is a rare disorder of bladder inflammation with eosinophils infiltration diagnosed by pathologic examination. The etiology is unclear despite the past identification of many factors contributing to this disease. Eight patients with eosinophilic cystitis were reported. The intact history, clinical manifestation, radiological examination and response to therapy were all evaluated. The results showed that 7 patients developed hematuria, 6 patients were with dysuria, 4 patients with frequency and 4 patients with urine retention. Seven patients had abnormal urinalysis but no positive finding in culture. Radiological findings revealed that one patient had bladder mass lesions and upper urinary tract dilation. Cystoscopic examination was performed in every patient and showed mass-like, edematous, ulcerative or hyperemic mucosa lesions. Cold-cup biopsy or transurethral resection of bladder lesions were all performed and could be the first priority to be considered. However, partial or total cystectomy should be taken into consideration when simple treatment failed to resolve this problem. Additionally, antihistamines, steroids or antibiotics are given to control the clinical symptoms. The results of these treatments were good except for one case who suffered from recurrence but recovered after simple operation and oral therapy. Although good results were found concerning treatment, long-term follow-up is necessary.

Inorganic arsenic (iAs), a known human carcinogen, induces oxidative DNA damage and epigenetic silencing of tumor suppressor genes related to tumor progression. Chromodomain-helicase-DNA-binding protein 4 (CHD4) is a chromatin remodeling protein that acts on DNA repair and DNA methylation under oxidative damage in malignancies, but the role of CHD4 in arsenical urothelial carcinoma (UC) is unidentified. Our purpose was to observe CHD4-related repair effects on As-stimulated oxidative damage in human UC. The markers of oxidative DNA damage 8-hydroxy-2'-deoxyguanosine (8-OHdG) and CHD4 were investigated by immunohistochemistry in 45 UC tissues from non-blackfoot disease (BFD) areas and BFD areas respectively. The cellular mechanisms of CHD4 involved in the oxidative DNA repair and DNA methylation were evaluated by immunocytochemistry and western blot. The expressions of CHD4 and 8-OHdG were significantly increased in UC patients from the As-exposed areas. The underlying mechanism of CHD4-mediated DNA repair and DNA methylation involved the activation of zinc finger MYND-type containing 8 (ZMYND8) and DNA methyltransferase (DNMTs) in SV-HUC-1, T24 and BFTC-905 cells. These results highlight the potential clinical significance of CHD4 in UCs from BFD areas. The CHD4-mediated oxidative DNA repair and epigenetic DNA methylation in UC cells stimulated by arsenic was revealed. CHD4 might be used as a prognostic indicator in arsenical UC.

Neurofibromatosis (NF) is a hereditary autosomal dominant disorder. Von Recklinghausen first described NF in 1882, which is now classified as Neurofibromatosis 1 (NF-1). NF-1 is the most commonly encountered NF which affects 1 in 4000 persons. Clinical manifestations of NF-1 include: generalized cutaneous neurofibroma, pigmented skin patches (cafe-au-lait spots), pigmented iris hamartoma (Lisch nodules), skeletal abnormally, CNS tumors, etc. The subject of this case study is a young adult male with a huge plexiform neurofibroma involving both the liver and head regions. The head tumor measured 10 x 8 x 3.5 cm3 in size, weighted approximately 180g with overlying hyperpigmented skin and an underlying congenital skull defect. A CT scan and MRI of the head and neck revealed a well defined lobulated tumor and deformed external ear. A abdominal sonogram, CT scan and MRI showed a huge plexiform neurofibroma with liver invasion. Lisch nodules and multiple cafe-au-lait spots were also found. Surgical removal of the head tumor along with an external ear reconstruction was performed. Satisfactory cosmetic results and improved hearing were achieved.

Frozen section diagnosis rendered in 549 consecutive breast biopsies performed in 5 years in a single pathology laboratory was correlated with the final pathological diagnosis. There were no false positive reports among the 220 (40.1%) biopsies interpreted as benign lesions in paraffin sections. Among 329 (59.9%) malignant biopsies on paraffin sections, 3 cases were interpreted as benign lesions on frozen sections. Three false negatives included 2 ductal carcinoma in situ and one infiltrating ductal carcinoma associated with papillomatosis. The tumors were small and confined to the breast without any evidence of metastasis. There was a very good correspondence between the frozen section diagnosis and the paraffin section diagnosis (K = 0.98). The sensitivity of frozen section diagnosis was 99.1% and the clinical diagnostic specificity was 100%. Our results suggest that frozen section diagnosis is a highly reliable procedure, but small lesions (less than 1 cm in diameter, or non-palpable) should not be subjected to frozen section examination to avoid unnecessary loss of neoplastic tissue during the frozen section. The careful investigation of paraffin-embedded tissue is recommended for small breast lesions in breast conserving lumpectomy.

Pressure overload in the left ventricle of the heart follows a chronic and progressive course, resulting in eventual left heart failure and pulmonary hypertension (PH). The purpose of this research was to determine whether a differential pulmonary gene change of endothelin (ET)-1 and endothelial nitric oxide synthase (eNOS) occurred in adult rats with left ventricular overload. Eight groups of eight rats each were used (four rats with banding and four rats with sham operations). The rats underwent ascending aortic banding for 1 day, 2 weeks, 4 weeks, and 12 weeks before sacrifice. Significant medial hypertrophy of the pulmonary arterioles developed in two groups (4 and 12 weeks). Increased pulmonary arterial pressures were noted in three groups (1 day, 4 weeks, and 12 weeks). The aortic banding led to significant increases in pulmonary preproET-1 messenger RNA (mRNA) at 1 day and 12 weeks, and in pulmonary eNOS mRNA at 1 day and 12 weeks. In addition, there was increased pulmonary eNOS content at 1 day and 12 weeks in the banded rats, and increased lung cGMP levels were observed at 1 day. Increased lung ET-1 levels were also noted at 1 day (banded, 310 +/- 12 ng/g protein; sham, 201 +/- 12 ng/g protein; P < 0.01), 4 weeks (banded, 232 +/- 12 ng/g protein; sham, 201 +/- 12 ng/g protein; P < 0.01) and 12 weeks (banded, 242 +/- 12 ng/g protein; sham, 202 +/- 12 ng/g protein; P < 0.01). This indicates that the upregulated expression of ET-1 developed at least 4 weeks before eNOS expression in the course of PH, and, thus, medication against ET-1 could play a crucial role in treating PH with cardiac dysfunction secondary to aortic banding.

Abstract: We reported a 59-year-old female who diagnosed with right breast invasive lobular carcinoma (pT2N0M0, stage IIA) and received modified radical mastectomy with adjuvant chemotherapy and radiotherapy (50 Gy) in 1999. But, she found T10-spine metastasis and received palliative radiotherapy (30 Gy in 10 fractions) 3 years later. In 2012, she had a left abdominal mass and received abdominal wall tumor resection and a metaplastic invasive lobular carcinoma [estrogen receptor (ER)(+), progesterone receptor (PR)(−), human epidermal growth factor receptor 2 (HER2)(−) with positive surgical margin] was noted by pathological reports. In spite of hormone therapy, she experienced a left abdominal painless mass at the same location underneath the previous surgical scar in 2016. After surgical excision, computed tomography showed a residual left external oblique muscle 4.8 cm × 5.0 cm mass. Under the impression of right breast cancer with left external oblique muscle metastasis [metastatic invasive lobular carcinoma, rcT0N0M1, rpT0N0M1, stage IV (AJCC 7th staging)], she received post-operative radiotherapy 60 Gy in 30 fractions. She continued to receive chemotherapy and no evidence of abdominal recurrence till now.

Abstract Background Total mesorectal excision (TME) with or without neoadjuvant concurrent chemoradiotherapy (CCRT) is the treatment for rectal cancer (RC). Recently, the use of conventional laparoscopic surgery (LS) or robotic-assisted surgery (RS) has been on a steady increase cases. However, various oncological outcomes from different surgical approaches are still under investigation.Materials and methods This is a retrospective observational study comprising 300 consecutive RC patients who underwent various techniques of TME (RS, n = 88; LS, n = 37; Open surgery, n = 175) at a single center of real world data to compare the pathological and oncological outcomes, with a median follow-up of 48 months.Results Upon multivariate analysis, histologic grade ( P =0.048), tumor depth ( P =0.003), and pre-operative CCRT ( P =0.038) were the independent factors of circumferential resection margin (CRM) involvement. The Kaplan-Meier survival analysis determined RS, early pathologic stage, negative CRM involvement, and pathologic complete response to be significantly associated with better overall survival (OS) and disease-free survival (DFS) (all P &lt;0.05). Multivariable analyses observed the surgical method ( P =0.037), histologic grade ( P =0.006), and CRM involvement ( P =0.043) were the independent factors of DFS, whereas histologic grade ( P =0.011) and pathologic stage ( P =0.022) were the independent prognostic variables of OS.Conclusions This study determined that RS TME is feasible because it has less CRM involvement and better oncological outcomes than the alternatives have. The significant factors influencing CRM and prognosis depended on the histologic grade, tumor depth, and pre-operative CCRT. RS might be an acceptable option owing to the favorable oncological outcomes for patients with RC undergoing TME.

Middle ear cholesteatoma has a remarkable invasive activity accompanied by destruction of ossicles and temporal bone. Its aggressive growth and high tendency to recur have impact on the postoperative care of the patients. Proliferating cell nuclear antigen (PCNA) is a 36 KDa DNA-delta-polymerase-associated protein whose level of synthesis has been found to correlate directly with rates of cellular proliferation. In this present study, we used ABC (avidin-biotin complex) technique and monoclonal antibody to PCNA to evaluate the expression of PCNA in 37 cases of cholesteatoma epithelium and 21 cases of normal postauricular skin. The rate of PCNA-positive cells in basal, parabasal, and upper layer of cholesteatoma epithelium tissue is 78% (29 cases), 68% (25 cases), and 41% (15 cases). In each layer of the postauricular skin tissue is 71% (15 cases), 67% (14 cases) and 34% (7 cases). No statistical difference of expression of PCNA-positive cells exists between each layer of cholesteatoma epithelium and normal postauricular skin; however, a tendency of higher PCNA-positive cells in cholesteatoma epithelium was observed. Immunohistochemical method of PCNA has the advantages of spatial architecture preservation, the relative simplicity of the methodology and the rapid acquisition of results. Although the etiology and histopathology of the growth pattern and osteolytic activity of cholesteatoma are unclear, information on cell kinetics may assist in cholesteatoma classification and may help predict the risk of recurrence and bone destruction. The results of this report indicate that cholesteatoma has a similar proliferative activity to the normal postauricular skin, and cholesteatoma itself is not a real tumor, despite its clinical behavior, which is similar to neoplastic cells. It is necessary to further study whether the cell kinetic information we obtained from the PCNA immunohistochemical analysis provides a valuable tool in accessing the prognosis of the cholesteatoma.

Herein we are reporting a case of simultaneous occurrence of renal and pancreatic foreign body granuloma due to retained gauze. The different imaging features of the two lesions make correct preoperative diagnosis difficult. Foreign body granulomas due to retained surgical gauze or sponges should be considered in patients who have previous histories of operations and who also have a mass in the surgical bed. Simultaneous occurrence of foreign body granuloma away from primary surgical field is also possible.

Tumorigenesis is the result of sequential or multiple genetic alterations. The overexpression or amplification of various oncogenes in diverse human brain tumors have been observed. While numerous studies on the immunohistochemical demonstration of EGFR-overexpression have been reported, little has been found in the literature about the c-erbB-2 protein in human astrocytic tumors. In the present study, we evaluated the expression of EGFR and c-erbB-2 protein in 33 astrocytic tumors with immunohistochemistry. According to the World Health Organization brain tumor classification, the study included 9 low-grade astrocytomas (grade 2), 15 anaplastic astrocytomas (grade 3), and 9 glioblastomas multiforme (grade 4). The positive EGFR immunoreactivity was detected in 28 (85%) of 33 tumors. The expression of EGFR increased with the grade of malignancy in low-grade astrocytomas (67%), anaplastic astrocytomas (87%), and glioblastomas (100%). For the expression of c-erbB-2 protein, 17 (51.5%) of 33 tumors were positive immunostain, including 3 low-grade astrocytomas (37.5%), 9 anaplastic astrocytomas (81.8%), and 5 glioblastomas (62.5%). Different degrees of immunoreactivity for c-erbB-2 protein were found in variant grades of astrocytomas. However, the positive immunostain of EGFR displayed moderate or strong reactivity. The coexpression of EGFR and c-erbB-2 protein was found in 17 (15.5%) of 33 tumors. The results emphasize that the overexpression of EGFR parallels astrocytoma progession and higher frequency of c-erbB-2 immunoreactivity was seen in snaplastic astrocytomas and glioblastomas than in low-grade astrocytomas.

A 36-year-old woman had suffered from epigastric fullness for half a year. A splenic mass was found by ultrasonography. She was treated with splenectomy. Inflammatory pseudotumor of the spleen was diagnosed pathologically. This benign tumor in the spleen is extremely rare. To our knowledge, only 67 cases had been reported in the literature. Recognition of this rare entity is important because it may mimic splenic malignancy clinically and radiographically.

Spinal venous malformations are vascular malformations of the central nervous system. Progressive or sudden neurological deficits can result in the deterioration of the quality of life, owing to the nature of the disease. Surgery is recommended after 2–6 weeks in patients with acute symptoms, to facilitate better surgical planning. Steroids are administered during the preoperative planning and rehabilitation period. However, the patient reported in this study developed a perforated peptic ulcer 1 week after surgery and died due to sepsis. Therefore, we questioned the optimum time for surgery, i.e., we considered whether early or delayed surgery would result in better patient outcomes.

A 75-year-old female patient with poorly-controlled diabetes who developed rhino-cerebral mucormycosis and acute stroke is reported. The magnetic resonance (MR) imaging revealed acute stroke in the territory of left anterior cerebral artery territory and corresponding steno-occlusive lesion on MR angiography. Proton MR spectroscopy (MRS) of her brain was obtained with chemical shift imaging, which revealed increased choline peak at 3.2 ppm and a succinate peak at 2.4 ppm. This was not usually present in patients with stroke. Cerebritis caused by mucormycosis may be diagnosed with the aid of MRS. Mucormycosis is a phycomycosis from the genus Mucor. Involvement of the central nervous system by mucormycosis may occur in the uncontrolled diabetic or immunocompromised patients and still attains a high mortality rate if an early diagnosis is not achieved [1]. Therefore an early diagnosis is essential and does improve the prognosis [2, 3]. We present a case with rhinocerebral mucormycosis complicated with left anterior cerebral artery infarction. Magnetic resonance spectroscopy (MRS) assisted diagnosis of superimposed cerebritis in the infarcted brain parenchyma. We propose that magnetic resonance (MR) images combined with MRS can improve early detection of cerebral mucormycosis. In our review of literature, this is the first presentation of in vivo MRS concerning infarction superimposed with mucormycosis cerebritis.

The role of p53 gene mutations in the formation or progression of human astrocytic tumors is controversial. We studied the distribution pattern of p53 immunoreactivity and analyzed p53 gene mutations to define the significance of p53 gene mutations in astrocytoma tumorigenesis or malignant progression. Twenty-three astrocytic tumors were evaluated with immunohistochemistry, single-strand conformation polymorphism (SSCP) analysis, and sequence analysis. We also searched MEDLINE to collect data on p53 gene mutation frequencies in astrocytic tumors in order to evaluate the association of p53 mutations and tumor grade. Strong immunoreactivity with a diffuse clustering pattern was found in three of five glioblastomas and seven of 12 anaplastic astrocytomas. Three of four low-grade astrocytomas were immunonegative. The p53 immunopositive cells in the only positively staining low-grade astrocytoma in our study appeared sparsely scattered. The results of immunostaining suggested that clonal expansion was associated with astrocytoma progression. Mutations of the p53 gene were detected in four of the 23 astrocytomas (one glioblastoma and three anaplastic astrocytomas). In the genetic data analysis, 76 of 367 astrocytomas had p53 gene mutations. A significantly greater p53 gene mutation frequency was found in anaplastic astrocytomas or glioblastomas than in the low-grade astrocytomas. The results of these immunohistochemical and genetic studies support the view that p53 gene mutation is associated with the malignant progression from low-grade to high-grade astrocytomas rather than with tumor initiation or promotion.

Pulmonary mucoepidermoid carcinoma is a rare disease with a common presentation as an intraluminal mass leading to airway obstruction. We reported a 26-year-old woman who suffered from hemoptysis during or a few days before every menstrual period, and spontaneous pneumothorax. The initial clinical impression was thoracic endometriosis syndrome due to the presence of catamenial hemoptysis. However, computed tomography revealed a suspicious mass-like lesion in the left main bronchus and bronchoscopy confirmed the presence of an endobronchial tumor. She underwent sleeve bronchial resection of the tumor and pathological examination revealed low-grade mucoepidermoid carcinoma. She had an uneventful recovery and was continuously followed in our clinic. For patients presenting with catamenial hemoptysis, endobronchial tumor should be considered, in addition to thoracic endometriosis syndrome.

We describe a 52-year-old man who presented with hemoptysis. The chest radiograph showed a widened carinal angle, and the computed tomography (CT) of the chest revealed subcarinal lymphadenopathy with invasion into the trachea and left main bronchus. A mass at the main carina with nearly total obstruction of the left main bronchus was found with bronchoscopy. Biopsy of the lesion revealed anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (ALCL). No other organ or lymph node involvement was found on positron emission tomography. The patient had a complete remission after treatment with chemotherapy and radiotherapy. He has been followed up in the clinic without incident for more than a year. Endotracheal/endobronchial ALCL is very rare. All reported patients were younger than 30 years, and all of them had ALK-positive ALCL. To our knowledge, ours is the first case of endobronchial ALCL in a patient more than 50 years old and with ALK-negative ALCL. This case suggests that lymphoma should be included in the differential diagnoses of endobronchial tumor in older adults.

Previously, 7-[2-[4-(4-Nitrobenzene)piperazinyl]ethyl]-1,3-dimethylxanthine (KMUP-3) has been shown to induce aortic smooth muscle relaxation through KATP channel opening and endothelial nitric oxide synthase (eNOS) enhancement. We further investigate the cardioprotective effect of KMUP-3 in myocardial infarction (MI) rats.

A unique case of pilocytic astrocytoma (PCA) with leptomeningeal dissemination occurring after surgery in a 2-year-old boy who presented with progressive left-sided weakness is reported. A cranial magnetic resonance imaging (MRI) disclosed a lesion with a cystic component in the right thalamus and basal ganglia. The lesion was subtotally resected and diagnosed by the pathology department to be a PCA. An MRI 16 days after surgery revealed a residual tumor with a tumor seeding along the surgical tract and in the meninges. The patient then underwent chemotherapy and a cranial MRI. Eleven months later the patient did not disclose any residual or additional lesions. The patient continues to do well at the time of this writing. This case illustrates a unique instance of leptomeningeal dissemination through the surgical tract of a resected cerebral PCA in a child.

Lung cancer is the leading cause of cancer death in the world [1-2]. In patients with lung cancer, metastasis to the bone, brain, liver and adrenal gland is most frequently found [2]. Gastrointestinal metastasis is not as frequently reported [1]. Among these patients, bleeding, anemia, and acute abdomen were the common presentations. Intussusception is a relatively rare but emergent condition. Aggressive investigation and early surgery are the only methods for providing palliation to patients with gastrointestinal metastasis. However, morbidity and mortality remain high and the prognosis is poor. Herein, we report a lung adenocarcinoma patient who presented acute abdomen; the final diagnosis was the unexpected small bowel intussusception caused by metastasis. We report this rare case and review the literature.

The title of the following article was incorrectly published: Cheng-Che E Lan, Ching-Shuang Wu, Shu-Mei Huang, Hsuan-Yu Kuo, I-Hui Wu, Chien-Hui Wen, Chee-Yin Chai, Ai-Hui Fang, and Gwo-Shing Chen. High-Glucose Environment Inhibits p38MAPK Signaling and Reduces Human β-3 Expression in Keratinocytes. Mol. Med. 2011;17(7–8):771–9.

On the Cover: September 2012 marked the beginning of the outbreak of infections associated with epidural and intra-articular injections that were contaminated with the black mold Exserohilum rostratum.Exserohilum fungal hyphae (red) in brain sample of a fatal case as seen using polyfungal immunohistochemistry. (See page 881.

Lercanidipine, a calcium channel antagonist, is currently employed in the treatment of essential hypertension and angina pectoris. The purpose of this study was to elucidate the anti-proliferative effect of lercanidipine and to investigate the molecular role of this agent. Both in vitro studies and in a balloon injury rat carotid artery model were employed to study the effect of lercanidipine on smooth muscle cell proliferation. Lercanidipine-inhibited rat vascular smooth muscle cell (VSMC) proliferation and migration in a dose-dependent manner following stimulation of VSMC cultures with 10% fetal bovine serum (FBS) and 20 ng/ml platelet-derived growth factor (PDGF)-BB. FBS- and PDGF-BB-stimulated intracellular Ras, MEK1/2, ERK1/2, proliferative cell nuclear antigen (PCNA), and Akt activations were significantly inhibited by lercanidipine; however, lercanidipine did not affect FBS- and PDGF-BB-induced STAT3 phosphorylation. Lercanidipine also inhibited PDGF-receptor b chain phosphorylation and reactive oxygen species (ROS) production induced by PDGF-BB. Lercanidipine blocked the FBS-inducible progression through the G0/G1 to the S-phase of the cell cycle in synchronized cells. In vivo, 14 days after balloon injury, treatment with 3 and 10 mg/kg lercanidipine resulted in significant inhibition of the neointima/media ratio. Suppression of neointima formation by lercanidipine was dependent on its influence on ERK1/2 phosphorylation. These results demonstrate that lercanidipine can suppress the proliferation of VSMCs via inhibiting cellular ROS, Ras-MEK1/2- ERK1/2, and PI3K-Akt pathways, and suggesting that it may have therapeutic relevance in the prevention of human restenosis.

Of the upper urinary tract (UUT) transitional cell carcinomas (TCCs), only about 25% are ureteral TCC. Typical ureteral carcinoma symptoms are painless hematuria and flank pain. Bone metastasis of ureteral cancer is always directly invasive to nearby bone structures such as the spine, pelvis, and hip bone. Distal bone metastasis such as that in the tibial bone, however, is rare. This report describes a female patient who initially presented with left early stage ureteral transitional cell carcinoma (pT1N0M0) after nephroureterectomy and bladder cuff excision in MK 92. She complained of low back pain and suspected combined radicular pain in MK94. Due to poor response to initial conservative treatment, the patient was eventually diagnosed with right tibial bone metastasis. Three years after surgical intervention chemotherapy to treat the metastasis, follow-up examination revealed stable condition. In clinical practice, accurate differential diagnosis is essential in patients with low back pain and low leg pain, HIVD with radicular pain, and metastatic bone lesions. Detailed patient history and physical and neurological examinations are essential. Further survey for other etiologies is indicated in patients who respond poorly to conservative treatment, particularly those with history of urinary tract cancer.

To investigate the correlation of HER-2 expression and oncological outcomes in patients treated with radical nephrouretectomy for upper tract urothelial carcinoma (UTUC).

[This corrects the article DOI: 10.18632/oncotarget.9841.].

Background: Many factors are thought to be associated with the development of cholesteatoma, while the mechanisms of its formation remain unclear. This study aimed to identify the potential mechanisms of the proliferation and growth of cholesteatoma by analysis of the differential expressions of proteins in cholesteatoma and retroauricular skin tissue collected from the same patients. Methods: The present study is a retrospective study performed in an academic medical center. Comparative proteomics analyses using two-dimensional gel electrophoresis (2-DE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS), in addition to immunohistochemical analysis, were conducted to identify differentially-expressed proteins in cholesteatoma tissue as compared with retroauricular skin tissue. Western blotting was also employed to verify the expression patterns of the specific proteins identified by 2-DE and to measure the changes in potential modulators related to cholesteatoma proliferation and growth. Results: Calreticulin (CRT) and annexin A2 (AnxA2) were identified as being differentially-expressed in cholesteatoma by 2-DE and LC-MS/MS, the results of which were in agreement with the results of immunohistochemical analysis and western blotting. Downregulation of CRT and AnxA2 were observed in cholesteatoma. Conclusion: Our data suggests that CRT and AnxA2 downregulation are seen in cholesteatoma compared to retroauricular skin. We speculate that the reduced expression of CRT and the persistent inflammatory response play important roles in the epithelial proliferation of cholesteatoma.

Muscle loss and weakness after a burn injury are typically the consequences of neuronal dysregulation and metabolic change. Hypermetabolism has been noted to cause muscle atrophy. However, the mechanism underlying the development of burn-induced motor neuropathy and its contribution to muscle atrophy warrant elucidation. Current therapeutic interventions for burn-induced motor neuropathy demonstrate moderate efficacy and have side effects, which limit their usage. We previously used a third-degree burn injury rodent model and found that irisin-an exercise-induced myokine-exerts a protective effect against burn injury-induced sensory and motor neuropathy by attenuating neuronal damage in the spinal cord. In the current study, spinal irisin gene delivery was noted to attenuate burn injury-induced sciatic nerve demyelination and reduction of neuromuscular junction innervation. Spinal overexpression of irisin leads to myelination rehabilitation and muscular innervation through the modulation of brain-derived neurotrophic factor and glial-cell-line-derived neurotrophic factor expression along the sciatic nerve to the muscle tissues and thereby modulates the Akt/mTOR pathway and metabolic derangement and prevents muscle atrophy.

Rationale: Angiomatosis is a rare non-neoplastic proliferative vascular lesion that typically develops during childhood or adolescence with a female predominance. Management of angiomatosis is challenging because of the manifestation of a wide variety of lesions as well as their invasive and highly recurrent nature. Patient concerns: We report the case of a 74-year-old man who presented with a right lower back mass that persisted for a decade. The mass progressively enlarged and had been painful in the previous month. Diagnosis: Computed tomography (CT) revealed suspected lipomatous sarcoma with invasion of the ribs, pleurae, and lung parenchyma. The final pathological examination revealed angiomatosis. Interventions: The patient underwent wide composite excision of the tumor along with excision of the pleura and lung nodules in the right lower and middle lobes via video-assisted thoracoscopic surgery (VAST). Fasciocutaneous rotational flap reconstruction was performed immediately after the wide composite excision and video-assisted thoracoscopic surgery (VAST). Outcomes: The patient recovered uneventfully, was discharged without complications, and tolerated the daily activities well. Lessons: Angiomatosis is a rare benign vascular tumor that frequently mimics malignancy. Even if the patient profile does not match the reported epidemiology of this disease, differential diagnosis should be considered. Complete resection is the mainstay of treatment for the prevention of recurrence.

In a rabbit model, transplantation of largely expanded microskin grafts (expansion ratio 25 X) were studied. In Group I, the autologous microskin grafts were transplanted onto the full-thickness skin defect on the back of a rabbit and were overlaid with Biobrane. In Group II, the autologous microskin grafts were mixed with allogeneic microdermal substance (expansion ratio 25 X) before the transplantation. The percentage of re-epithelialized area to the total grafted wound was analyzed by means of computerized planimetric analyses of photographs of the grafted wounds on days 11 and 13. Biopsies of the grafted wounds were done. On day 11, the mean percentage of Group I was 72.4% and that of Group II was 82.7%. On day 13, they were 82.3% in Group I and 92.3% in Group II. In Group II, the allogeneic dermal tissue did not cause obvious rejection in the neoepithelium. Histological features showed the existence of allogeneic dermal tissue in the grafted wound. The adding of largely expanded allogeneic dermal substance to autologous microskin grafts in Group II provided better circumstances than that in Group I for re-epithelialization of autologous mciroskin grafts.

Therapeutic ultrasound has been used in the treatment of osteoarthritis for the relief of symptom and improvement of functional status. In recent study, we found that ultrasound enhances cartilage repair in experimental early stage osteoarthritis, and prevents deteriorative changes in later stages. In the present study, we further investigate the bioeffects of ultrasound on cartilage matrix of experimental arthritis. Fifty-four rats with three different degrees of papain induced osteoarthritis classified by 99m-Tc pertechnetate bone scan were collected for ultrasound treatment. The changes in their arthritic severity after sonication treatment and two months after treatment were measured using 99m-Tc bone scan. The histopathological changes were evaluated through light microscope after disarticulation sections (H.E. stain), and the changes in mucopolysaccharide density in cartilage matrix were measured using a Optimas scanner analyzer after Alcian blue staining. The results showed that the density of mucopolysaccharide rose in the initial stage of induced arthritis, and decreased progressively in the later stage. The density of mucopolysaccharide increased upon complete sonication more for the treated rats than for the controls, and this was closely related with the improvement in histopathological findings, but inversely with the changes in arthritic severity. In conclusion, therapeutic ultrasound enhances mucopolysaccharide synthesis of arthritic cartilage, and results in the repair of arthritic cartilage in the early stage of induced arthritis and the prevention of deteriorative changes in later stages.

Purpose: To analyze treatment outcome and prognostic factors of patients with olfactory neuroblastoma. Materials and Methods: Seventeen patients with pathology-proven olfactory neuroblastoma diagnosed between March 1994 and October 2005 were analyzed retrospectively. Clinical charts, pathology reports, radiology images and radiotherapy records were reviewed. Patients' characteristics, details of treatment modalities and clinical outcome were collected. Sixteen patients were re-staged with three staging system including: Kadish, Dulguerov and the 6th AJCC staging system for nasal cavity and paranasal sinuses. Histo-pathological specimens of 17 patients were reviewed to define the tumor grading using Hyams' four-tier system. Results: There were 9 male and 8 female, age ranged from 14 to 74 years old. According to Kadish's classification, there were 3 stage A, 3 stage B and 10 stage C diseases. The most common symptom was epistaxis. Thirteen patients received treatment at our institute. A median follow-up time of 40.3 months (mean: 48.6 months), 6 patients were alive without disease and 4 were alive with disease. Locoregional failure occurred in 5 patients and distant metastases were noted in 2 patients. Five-year overall survival rate was 52.5% and 5-year disease free survival rate was 42%. Degree of surgery was the only significant prognostic factor in univariate analysis (p=0.021). Conclusion: In this study, surgical intervention to total removal of the tumor was the most significant prognostic factor. Adjuvant treatment such as radiotherapy was needed for advanced diseases, in which residual tumor was notified even after radical surgery. Radiotherapy combined with surgical resection was an effective modality for treatment of olfactory neuroblastoma; this combination could provide excellent local control. Most tumors were response to the initial radiotherapy at the range of 55 to 65 Gy. Elective neck irradiation was not needed routinely. Local recurrence might happen even 5 years later, and long-term follow-up should be mandated.

OBJECTIVE: Much research has discussed the expression of granulocyte colony-stimulating factor (G-CSF) in urothelial cancer but few clinical data are available. A significant proportion of bladder carcinomas have been reported to express G-CSF. Our study examined the role of G-CSF expression in bladder cancer. MATERIALS AND METHODS: From 1999 to 2006, we collected data on 56 cases who received a radical cystectomy at Kaohsiung Medical University Hospital. Clinical data including TNM stage, grade, laboratory data, and infective status were reviewed. Expressions of G-CSF in the tumors were detected by immunohistochemical staining. We examined the association of the expression of G-CSF with the tumor TNM stage, grade, and infectious status by Chi-squared or Fisher's exact test. RESULTS: The immunohistochemical staining for G-CSF was performed on tissues from 56 patients with bladder cancer after a radical cystectomy. All of the non-tumor parts of the urinary bladder negatively stained for G-CSF. We divided the results of staining into 2 parts: low and high. We found there was a negative association between the G-CSF expression intensity and patient postoperative survival (p=0.008). However, no significant relationships between G-CSF expression and tumor TNM stage or grade were identified. We did, however, find positive associations between G-CSF levels and preoperative leukocytosis and urinary tract infection (p=0.009 and 0.04, respectively). CONCLUSIONS: In the present study, G-CSF expression in bladder cancer was proven to be negatively associated with postoperative survival in patients who received a radical cystectomy. This cannot be explained by the invasiveness of the tumor when we compared the expression of G-CSF with the tumor TNM stage and grade. We also found that preoperative leukocytosis and urinary tract infection were positively associated with the intensity of G-CSF expression. Strict control of these problems may be beneficial to patients who are to receive a radical cystectomy.

Abstract The objective of this study is to characterize the oncogenic roles of a recently identified cancer-associated gene called YWHAZ (also known as 14-3-3 α/ζ ) in urothelial carcinomas of urinary bladder (UCUB). Based on a genomewide study, YWHAZ was found located at the 8q22.3 amplicon and its genetic amplification was predominantly detected in tumors at more advanced stages, muscle-invasive bladder cancer (MIBC). IHC staining confirmed the association of YWHAZ overexpression with higher tumor stages, lymph node/vascular invasion, and mitotic activity. Univariate and multivariate analyses further indicated the prognostic potential of YWHAZ for more aggressive cancer types. Both gene set enrichment analysis (GSEA) and STRING network studies suggest the involvement of YWHAZ in regulating caspase-mediated apoptosis. Ectopic expression of YWHAZ in bladder cells with low YWHAZ levels boosted cells becoming more tolerated toward chemical and ionizing radiation treatments. Gene knockdown by specific shRNA in cells with high YWHAZ levels attenuated the survival activity, resulting in cell growth suppression and cell death. Our data confirmed an essential role of YWHAZ in providing survival signals to sustain cell proliferation during chemo- or radio-therapy. Treatments based on anti-YWHAZ strategies may be beneficial for patients with YWHAZ overexpression. Citation Format: Jim Jinn-Chyuan Sheu, Chia-Cheng Yu, I-Hsuan Chen, Praveen Korla, Grace Ko, Chee-Yin Chai, Chien-Fong Li. YWHAZ amplification/overexpression defines aggressive bladder cancer and contributes to chemo-/radio-resistance via deregulation of caspase-mediated apoptosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 265.

Abstract Aims Chronic inflammation and cancer stem cells are known risk factors for tumorigenesis. The aetiology of hepatocellular carcinoma (HCC) involves a multistep pathological process characterised by chronic inflammation and hepatocyte damage but the correlation between HCC, inflammation and cancer stem cell remains unclear. In this study, we examined the role of hepatic progenitor cells in a mouse model of chemical-induced hepatocarcinogenesis to elucidate the relationship between inflammation, malignant transformation and cancer stem cells. Methods and results We used diethylnitrosamine (DEN) to induce liver tumour and scored for H&amp;E and reticulin staining, and also immunohistochemistry staining for OV-6 expression and analysed the statistical correlation between each other. DEN progressively induced inflammation at 7 week 7 (40%, 2/5), week 27 (75%, 6/8), week 33 (62.5%, 5/8) and week 50 (100%, 12/12). DEN progressively induced malignant transformation at week 7 (0%, 0/5), week 27 (87.5%, 7/8), week 33 (100%, 8/8) and week 50 (100%, 12/12). Data obtained showed that DEN progressively induced high-levels of OV-6 expression at week 7 (20%, 1/5), week 27 (37.5%, 3/8), week 33 (50%, 4/8) and week 50 (100%, 12/12). DEN-induced inflammation, malignant transformation and high-level OV-6 expression in hamster liver as shown above and applying Spearman’s correlation to the data showed that expression of OV-6 was significantly correlated to inflammation ( p = 0.001) and malignant transformation ( p &lt; 0.001) Conclusions There was a significant correlation between number of cancer stem cells, inflammation and malignant transformation in a DEN-induced model of hepatic carcinogenesis in the hamster.

Background Pulmonary artery hypertension (PAH) is a life-threatening and deteriorating disease with no promising therapy available currently due to its diversity and complexity.An imbalance between vasoconstriction and vasodilation has been proposed as the mechanism of PAH.Angiotensin-converting enzyme 2 (ACE2), which catalyzes the hydrolysis of the vasoconstrictor angiotensin (Ang) II into the vasodilator Ang-(1-7), has been shown to be an important regulator of blood pressure and cardiovascular diseases.Herein we hypothesized diminazene aceturate (DIZE), an ACE2 activator, could ameliorate the development of PAH and pulmonary vascular remodeling.Methods A murine model of PAH was established using left pneumonectomy (PNx) on day 0 followed by injection of a single dose of the VEGF receptor-2 inhibitor SU5416 (25mg/kg) subcutaneously on day 1.All hemodynamic and biochemical measurements were done at the end of the study on day 42.Animals were divided into 4 groups (n= 6/group): (1) sham-operated group, (2) vehicle-treatment group (SuPNx42), (3) early treatment group (SuPNx42/DIZE1-42) with DIZE at 15 mg/kg/day, subcutaneously from day 1 to day 42, and (4) late treatment group (SuPNx42/DIZE29-42) with DIZE from day 29-42.Results In both the early and late treatment groups, DIZE significantly attenuated the mean pulmonary artery pressure, pulmonary arteriolar remodeling, and right ventricle brain natriuretic peptide (BNP), as well as reversed the overexpression of ACE while up-regulating the expression of Ang-(1-7) when compared with the vehicle-treatment group.In addition, the early treatment group also significantly decreased plasma BNP and increased the expression of eNOS.Conclusions ACE2 activator has therapeutic potentials for preventing and attenuating the development of PAH in an animal model of left pneumonectomy combined with VEGF inhibition.Activation of ACE2 may thus be a useful therapeutic strategy for the treatment of human PAH.

Abstract Total mesorectal excision (TME) with or without neoadjuvant concurrent chemoradiotherapy (CCRT) is the treatment for rectal cancer (RC). Recently, the use of conventional laparoscopic surgery (LS) or robotic-assisted surgery (RS) has been on a steady increase cases. However, various oncological outcomes from different surgical approaches are still under investigation.Materials and methods This is a retrospective observational study comprising 300 consecutive RC patients who underwent various techniques of TME (RS, n = 88; LS, n = 37; Open surgery, n = 175) at a single center of real world data to compare the pathological and oncological outcomes, with a median follow-up of 48 months.Results Upon multivariate analysis, histologic grade ( P =0.048), tumor depth ( P =0.003), and pre-operative CCRT ( P =0.038) were the independent factors of circumferential resection margin (CRM) involvement. The Kaplan-Meier survival analysis determined RS, early pathologic stage, negative CRM involvement, and pathologic complete response to be significantly associated with better overall survival (OS) and disease-free survival (DFS) (all P &lt;0.05). Multivariable analyses observed the surgical method ( P =0.037), histologic grade ( P =0.006), and CRM involvement ( P =0.043) were the independent factors of DFS, whereas histologic grade ( P =0.011) and pathologic stage ( P =0.022) were the independent prognostic variables of OS.Conclusions This study determined that RS TME is feasible because it has less CRM involvement and better oncological outcomes than the alternatives have. The significant factors influencing CRM and prognosis depended on the histologic grade, tumor depth, and pre-operative CCRT. RS might be an acceptable option owing to the favorable oncological outcomes for patients with RC undergoing TME.

Abstract Background: Many factors are thought to be associated with the development of cholesteatoma, while the mechanisms of its formation remain unclear. This study aimed to identify the potential mechanisms of the proliferation and growth of cholesteatoma by analysis of the differential expressions of proteins in cholesteatoma and retroauricular skin tissue collected from patients. Methods: Comparative proteomics analyses using two-dimensional gel electrophoresis (2-DE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS), in addition to immunohistochemical analysis, were conducted to identify differentially-expressed proteins in cholesteatoma tissue as compared with retroauricular skin tissue. Western blotting was also employed to verify the expression patterns of the specific proteins identified by 2-DE and to measure the changes in potential modulators related to cholesteatoma proliferation and growth. Results: Calreticulin (CRT) and annexin A2 (AnxA2) were identified as being differentially-expressed in cholesteatoma by 2-DE and LC-MS/MS, the results of which were in agreement with the results of immunohistochemical analysis and western blotting. Downregulation of CRT and AnxA2 were observed in cholesteatoma. Conclusion: Our data suggested that CRT and AnxA2 were associated with cholesteatoma. We speculated that the reduced expression of CRT and the persistent inflammatory response play important roles in the epithelial proliferation of cholesteatoma.

We report on a 6 yr 7 m-old girl who had suffered from recurrent oral ulcers since July, 2000. Anal ulcers were also noted initially, and arthralgia was observed. Skin testing (pathergy test) showed only mild erythematous changes over the test area. HLA typing revealed HLA-B56. Intestinal symptoms included watery diarrhea with occasional blood. No ocular involvement was found. Her ailment was diagnosed as incomplete Behçet's disease with intestinal involvement. Diagnosis of Behçet's disease in childhood is a challenge and there are only a few studies on juvenile Behçet's disease (JBD) in the literature, with only a small number of patients. According to the literature, Behçet's disease in childhood is characterized by a low incidence of ocular lesion and a high incidence of intestinal involvement, as exhibited in this case.

The occurrence of pneumatosis cystoides intestinalis (PCI) in the gastrointestinal tract is rare. Among the cases already documented in the English language literature, the association of PCI with jejunal diverticulosis has only been mentioned once or twice. We herein report a case of a 63-year-old woman who had both entities concurrently in a segment of the jejunum. What is important to note is the relationship of PCI to the diverticulosis and its possible pathogenesis. Through histological examination and review of related articles, we are convinced that a mechanical theory plays a pivotal role when both diseases occur in the same segment of intestine and are compounded by obstruction or impaired peristalsis. This finding, when properly applied to PCI in other settings, helps to resolve the pathogenesis of PCI and other related gas-filled cysts.

We would like to apply 3 corrections to our published paper [[1]Hsu Y.C. Luo C.W. Huang W.L. Wu C.C. Chou C.L. Chen C.I. et al.BMI1-KLF4 axis deficiency improves responses to neoadjuvant concurrent chemoradiotherapy in patients with rectal cancer.Radiother Oncol. 2020; 149 (Epub 2020 Jun 24. PMID: 3259289): 249-258https://doi.org/10.1016/j.radonc.2020.06.023Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar]. The reason for the correction #1 is that Figure legend 2C should be Figure legend 2D, and Figure legend 2D should be Figure 2C. Correction #2 is that Figure 4A was misplaced with Figure 4B. Correction #3 is that there is a typo error in the Figure legend 4A. These changes do not change on the results and conclusions of our paper. We apologize for any inconvenience caused.#1 Figure 2. Depletion of BMI1 increases radiosensitivity of HCT-116 cells and leads to a reduction in expression of the KLF4 gene. (A) Cells (500 cells/dish) were exposed to 2 Gy irradiation (IR), 5-fluorouracil (5-FU; 2.5 µM), or IR (2 Gy) + 5-FU (2.5 µM) for 2 weeks and clonogenic activity was evaluated. Statistical analysis was performed using one-way ANOVA. (B) Cells were treated with IR (2 Gy), 5-FU (2.5 µM), or IR (2 Gy) + 5-FU (2.5 µM) and sphere formation was evaluated 14 d later for the formation of 1st generation spheres. Second generation of spheres was measured 14 d after subculture of 1st generation spheres. The experiments were repeated three times. Scare bar, 100 μm (*p < 0.05). (C) Expression levels of KLF4 mRNA in HCT-116 and BMI1-depleted cells were determined by real time qPCR. Columns represent the mean results from PCR assays performed in triplicate and normalized to GAPDH. (*p < 0.05). (D) Indicated proteins in HCT-116 cells were determined by western blotting analysis. (E) ChIP-qPCR analysis was performed to investigate the status of H3K4m3, H3K27m3, and BMI1 in the KLF4 gene promoter. The experiments were repeated three times. (*p < 0.05).#2 #3 Figure 4. BMI1 expression is positively correlated with KLF4 expression in rectal cancer. (A) Parental SW48 cells, BMI1 overexpressing SW48 cells, parental Caco-2 cells, and BMI1-depleted Caco-2 cells were treated with 2 Gy irradiation to study clonogenic activity. Data were calculated using paired t-test. *Indicated p < 0.05. (B) Representative images of colon tumor tissues with high and low expression of BMI1 and KLF4 in the same patients who received CCRT. Original magnification: ×200, scale bar: 100 μm. The associations between BMI1 and KLF4 and were determined by X2 analysis. The p-values are shown. BMI1-KLF4 axis deficiency improves responses to neoadjuvant concurrent chemoradiotherapy in patients with rectal cancerRadiotherapy and OncologyVol. 149PreviewColorectal cancers (CRCs) remain the most prevalent malignancies worldwide [1] with incidences increasing approximately by 22% over the past 10 years among patients <50 years of age, primarily due to a trend in greater numbers of rectal and distal colon tumors [2]. Neoadjuvant concurrent chemo-radiotherapy (CCRT) prior to surgery has been recommended for patients with locally advanced rectal cancer since the addition of fluorouracil-based chemotherapy might sensitize cells to the local radiation effect and eradicate micro-metastases, thereby further increasing the pathologic complete response rate [3]. Full-Text PDF

The difference of prognosis in patients with the same WHO grade of astrocytic tumors suggests that such tumors comprise a heterogeneous group in biological behavior. The correlation between p53 immunoreactivity and prognosis has often been reported but remains controversial. From the perspective of clonal expansion of p53 immunopositive cells, the distribution patterns of p53 immunoreactivity can be divided into four types: negative, scattered, focally clustered, and diffusely clustered. The survival rate was evaluated by classifying the p53 immunoreactivity into two groups: the significantly immunopositive patterns (focally and diffusely clustered types) and the significantly immunonegative patterns (negative and scattered types). The survival analysis showed a highly significant difference between these two patterns within the same WHO grade of astrocytic tumors (p = 0.0185). Our studies demonstrate that the distribution patterns of p53 immunoreactivity, which reflect the trends of clonal expansion of p53 immunopositive cells, are significantly valuable in predicting the prognosis of patients with the same WHO grade of astrocytic tumors.

BACKGROUND: The clinical characteristics of cholesteatomas, namely invasion, migration, altered differentiation, aggressiveness, and easy recurrence, are traits typically associated with the neoplastic cells. Using the proliferating cell nuclear antigen (PCNA) immunohistochemical staining method, we attempted to compare the proliferative features of human middle ear cholesteatoma with tympanic membrane of chronic otitis media (COM) and normal postauricular skin and to delineate the possible role of this immunohistochemical staining method in assessing the middle ear cholesteatoma. METHODS: We used ABC (avidin-biotin complex) technique and monoclonal antibody to PCNA to evaluate the expression of PCNA in 37 cases of cholesteatoma epithelium, 7 cases of tympanic membrane of chronic otitis media, and 21 cases of normal postauricular skin. RESULTS: The PCNA-positive cell rate in basal, parabasal, and upper layer of each cholesteatoma epithelium tissue was 78%, 68%, and 41% respectively. In the epithelium of the tympanic membrane, PCNA-positive cell rate in basal, parabasal, and upper layer was 86%, 71%, and 43% respectively. The PCNA-positive cell rate in normal postauricular skin tissue was 71%, 67%, and 34% respectively. The results of this report indicate that the proliferative activity in cholesteatoma is similar to that of the tympanic membrane of chronic otitis media and normal postauricular skin (P＞0.05). CONCLUSION: we found that cholesteatoma and tympanic membrane have a higher PCNA-positive cell rate than normal postauricular skin, but no statistical significance was observed among the epithelium layer. We conclude that despite its clinical behavior, which is similar to neoplastic cells, cholesteatoma itself is not a real tumor.

A 56 year-old lady presented a slowly growing tumor in left lacrimal sac area for 3 years. This tumor finally resulted in a prominent left unilateral telecanthus. The CT scan showed a large well encapsulated, homogenous tumor in left lacrimal sac area with an expanded fossa. At the first visit, lacrimal irrigation was patent without regurgitated bleeding. One and a half years later, lacrimal irrigation showed obstruction with much aspirated blood from irrigation needle. Although tumor excision and dacryocystorhinostomy had been attempted, severe hemorrhage from the tumor and the uncertain report from the frozen section of the tumor turned the operation to a dacryocystectomy. The detached medial canthal ligament was reattached to a titanium miniplate, which was fixed to the frontal process of maxillary bone. Jones tube was not inserted in the operation, because the frozen section could not rule out a malignancy. The subsequent histopathological study revealed an inflammatory pseudotumor. In a follow-up for 10 months postoperatively, epiphora was not a particular complaint. The unilateral telecanthus has been corrected with the simple and effective reconstruction method which used the titanium miniplate as a base for reattachment of medial canthal ligament.