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Background Danshen is a common traditional Chinese medicine used to treat neoplastic and chronic inflammatory diseases in China. However, the effects of Danshen on human oral cancer cells remain relatively unknown. This study investigated the antiproliferative effects of a Danshen extract on human oral cancer SAS, SCC25, OEC-M1, and KB drug-resistant cell lines and elucidated the possible underlying mechanism. Methods We investigated the anticancer potential of the Danshen extract in human oral cancer cell lines and an in vivo oral cancer xenograft mouse model. The expression of apoptosis-related molecules was evaluated through Western blotting, and the concentration of in vivo apoptotic markers was measured using immunohistochemical staining. The antitumor effects of 5-fluorouracil and the Danshen extract were compared. Results Cell proliferation assays revealed that the Danshen extract strongly inhibited oral cancer cell proliferation. Cell morphology studies revealed that the Danshen extract inhibited the growth of SAS, SCC25, and OEC-M1 cells by inducing apoptosis. The Flow cytometric analysis indicated that the Danshen extract induced cell cycle G0/G1 arrest. Immunoblotting analysis for the expression of active caspase-3 and X-linked inhibitor of apoptosis protein indicated that Danshen extract-induced apoptosis in human oral cancer SAS cells was mediated through the caspase pathway. Moreover, the Danshen extract significantly inhibited growth in the SAS xenograft mouse model. Furthermore, the Danshen extract circumvented drug resistance in KB drug-resistant oral cancer cells. Conclusion The study results suggest that the Danshen extract could be a potential anticancer agent in oral cancer treatment.

// Cheng-Yu Yang 1, 6 , Chih-Kung Lin 3 , Chang-Huei Tsao 7, 8 , Cheng-Chih Hsieh 5 , Gu-Jiun Lin 4 , Kuo-Hsing Ma 4 , Yi-Shing Shieh 6 , Huey-Kang Sytwu 1, 7 and Yuan-Wu Chen 1, 2, 6 1 Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan 2 Department of Oral and Maxillofacial Surgery, Tri-Service General Hospital, Taipei, Taiwan 3 Division of Anatomic Pathology, Taipei Tzu Chi Hospital, Taipei, Taiwan 4 Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan 5 Department of Pharmacy Practice, Tri-Service General Hospital, Taipei, Taiwan 6 School of Dentistry, National Defense Medical Center, Taipei, Taiwan 7 Graduate Institute of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan 8 Department of Medical Research, Tri-Service General Hospital, Taipei, Taiwan Correspondence to: Yuan-Wu Chen, email: h6183@yahoo.com.tw Keywords: patient-derived tumor xenograft, LSD1, melatonin, oral cancer, cell proliferation Received: June 16, 2016 Accepted: March 08, 2017 Published: April 04, 2017 ABSTRACT Aberrant activation of histone lysine-specific demethylase (LSD1) increases tumorigenicity; hence, LSD1 is considered a therapeutic target for various human cancers. Although melatonin, an endogenously produced molecule, may defend against various cancers, the precise mechanism involved in its anti-oral cancer effect remains unclear. Patient-derived tumor xenograft (PDTX) models are preclinical models that can more accurately reflect human tumor biology compared with cell line xenograft models. Here, we evaluated the anticancer activity of melatonin by using LSD1-overexpressing oral cancer PDTX models. By assessing oral squamous cell carcinoma (OSCC) tissue arrays through immunohistochemistry, we examined whether aberrant LSD1 overexpression in OSCC is associated with poor prognosis. We also evaluated the action mechanism of melatonin against OSCC with lymphatic metastases by using the PDTX models. Our results indicated that melatonin, at pharmacological concentrations, significantly suppresses cell proliferation in a dose- and time-dependent manner. The observed suppression of proliferation was accompanied by the melatonin-mediated inhibition of LSD1 in oral cancer PDTXs and oral cancer cell lines. In conclusion, we determined that the beneficial effects of melatonin in reducing oral cancer cell proliferation are associated with reduced LSD1 expression in vivo and in vitro .

Objectives This study aimed to evaluate the adverse clinicopathologic features of oral squamous cell carcinoma (OSCC), including margin status, depth of invasion, lymphovascular invasion, perineural invasion, and extranodal extension that significantly affect survival outcomes. Materials and methods This retrospective cross-sectional study included 341 patients with OSCC who underwent therapeutic surgical treatment in Taiwan. The Kaplan–Meier method was used to estimate survival outcomes. A multivariable Cox regression model was used to evaluate the associations of various clinicopathologic features with 5-year overall survival (OS) outcomes in patients with pN0 and pN+ tumors. Results Overall, the patients had 5-year OS and progression-free survival rates of 60.0 and 47.9%, respectively. In the pN0 group, the multivariate analysis identified a positive margin (odds ratio [OR] = 16.3, 95% confidence interval [95% CI]: 3.7–72.3; P = 0.001), depth of invasion >5 mm (OR = 2.1, 95% CI: 1.2–3.7; P = 0.012), presence of lymphovascular space invasion (OR = 5.4, 95% CI: 1.3–22.0; P = 0.018), and presence of perineural invasion (OR = 4.3, 95% CI: 1.7–11.1; P = 0.002) as independent and significant prognosticators of OS. In the pN+ group, only the presence of extranodal extension independently predicted OS (OR = 1.7, 95% CI: 1.1–2.7; P = 0.0026). Conclusions When determining survival prognosis for patients with a pN0 status, we recommended including all adverse features. In contrast, extranodal extension was the most important prognostic factor for patients with a pN+ status.

Background: Biological and prognostic roles of programmed death ligand-1 (PD-L1) remain unclear in oral squamous cell carcinoma (OSCC). The controversies role of tumor microenvironmental IFN-γ, pivotal roles in host responses to malignant cells, in oral cancer growth and PD-L1 expression was under-investigated. We examined the mechanism of PD-L1 regulation with focus on interferon gamma in vitro and in clinical samples. Triptolide is the bioactive compound isolated from Tripterygium wilfordii, which has been reported exhibit anti‑inflammatory and antitumor activities. Moreover, we investigated whether TPL affected suppression of PD-L1 is involved in its anti-cancer activity. Methods: The PD-L1 expressions were analyzed by immunohistochemistry in 135 tissues samples. We analysed the production of IFN-γ at oral cancer cell by enzyme-linked immunosorbent assay (ELISA) analysis. IFN-ϒ on oral cancer cell proliferation were examined. We investigated the anticancer of the TPL on human oral cancer by targeted PD-L1 in vitro and patient-derived tumor xenograft (PDTX) models. Findings: PD-L1 overexpression was significant in the tumor site of oral cancer (P < .01). IFN-γ driven the PD-L1 expression oral cancer cells in a dose-dependent manner. The TPL inhibits tumor growth in oral cancer PDTX model with suppressing the PD-L1 expression. The TPL also suppresses the oral cancer cell PD-L1 expression in an interferon-gamma microenvironment. Interpretation: Our results provide evidence for clinical development of PD-L1 targeting therapy in OSCC treatment in future. Funding Statement: This study was supported by research grants from Tri-Service General Hospital, Taiwan, Republic of China (grants Nos. TSGH-C106-004- 006-008-S05, TSGH-C107-008-S06, TSGH-C108-007-008-S06), Ministry of Science and Technology, Taiwan, Republic of China (grants No. MOST 105- 2314-MAB-106-090). Declaration of Interests: All authors have completed the disclosure forms and declare that: no support, financial or otherwise, has been received from any organization that may have an interest in the submitted work; and there are no other relationships or activities that could appear to have influenced the submitted work. Ethics Approval Statement: The experiments were conducted according to the ethical guidelines of the institutional review board (TSGH-2-102-05-111) of the National Defense Medical Center, Taiwan.

Biological and prognostic roles of programmed death ligand 1 (PD-L1) remain unclear in oral squamous cell carcinoma (OSCC). Moreover, the pivotal role of tumor microenvironmental interferon-gamma (IFN-γ) in host responses to malignant cells, oral cancer growth, and PD-L1 expression has not been adequately studied. Thus, PD-L1 expression in 130 OSCC samples was analyzed using immunohistochemistry, which was found significantly overexpressed at the tumor site (P

Background: Duodenal contents reflux through the pylorus into the stomach can cause chronic gastritis and gastric cancer. This study aims to propose a new classification of endoscopic findings of duodenogastric reflux (DGR) in symptomatic patients. Patients and Methods: Eighty‑eight patients with symptoms of DGR were included. Endoscopic findings, Helicobacter pylori, and mucosa pathological were recorded. Hepatobiliary scintigraphy was performed to quantify the DGR. Results: Among the 88 patients, 41 patients had normal mucosa (control group), 36 patients had bile lake (BL) (Group A), and 11 patients had bile stain (BS) (Group B). Group A significantly increases in postprandial DGR at 50 and 60 min. Group B significantly increases in fasting DGR at 50 and 60 min and postprandial DGR at 30, 40, 50, and 60 min. Group A and Group B had significant high intestine metaplasia and mucosal inflammation score than those in control group. Group B had a significantly higher incidence of gastric polyp than those patients in Group A and control group. Conclusions: Endoscopic findings of BS increased both fasting and postprandial DGR. BL had significant increased postprandial DGR. DGR increased the intestine metaplasia, mucosal inflammation, and gastric polyp in the stomach.

The effects of intravenous (IV) catheter gauge and pressurization of IV fluid (IVF) bags on fluid flow rate have been studied. However, the pressure needed to achieve a flow rate equivalent to that of a 16 gauge (G) catheter through smaller G catheters and the potential for endothelial damage from the increased kinetic energy produced by higher pressurization are unclear. Constant pressure on an IVF bag was maintained by an automatic adjustable pneumatic pressure regulator of our own design. Fluids running through 16 G, 18 G, 20 G, and 22 G catheters were assessed while using IV bag pressurization to achieve the flow rate equivalent to that of a 16 G catheter. We assessed flow rates, kinetic energy, and flow injury to rabbit inferior vena cava endothelium. By applying sufficient external constant pressure to an IVF bag, all fluids could be run through smaller (G) catheters at the flow rate in a 16 G catheter. However, the kinetic energy increased significantly as the catheter G increased. Damage to the venous endothelium was negligible or minimal/patchy cell loss. We designed a new rapid infusion system, which provides a constant pressure that compresses the fluid volume until it is free from visible residual fluid. When large-bore venous access cannot be obtained, multiple smaller catheters, external pressure, or both should be considered. However, caution should be exercised when fluid pressurized to reach a flow rate equivalent to that in a 16 G catheter is run through a smaller G catheter because of the profound increase in kinetic energy that can lead to venous endothelium injury.

Dysregulation of histone demethylase Jumonji-C domain-containing protein 5 (JMJD5) has been identified as a great effect on tumorigenesis. Silibinin is a commonly used anti-hepatotoxic drug and exhibits anticancer effect in various cancers. However, the antitumor mechanism between silibinin and JMJD5 in oral squamous cell carcinoma (OSCC) remains unclear. In this study, the clinical significance of JMJD5 on OSCC patients was assessed through tissue microarray. Furthermore, mice bearing patient-derived tumor xenografts (PDTXs) and tongue cancer cell lines were treated with silibinin and evaluated for tumor growth and JMJD5 expression. High expression of JMJD5 in oral cancer was significantly associated with tumor size (P = 0.0241), cervical node metastasis (P = 0.0001) and clinical stage (P = 0.0002), was associated with worse survival rate compared with that of the total cohort (P = 0.0002). Collectively the data indicate that JMJD5 expression may be suitable for detection of unfavorable prognosis in OSCC patients, based in part on its apparent role as a marker of metastasis. In addition, silibinin inhibits cancer growth in vitro and in PDTX models. Furthermore, metastasis-associated protein 1 (MTA1) could regulate the expression for JMJD5 and had a positive correlation with JMJD5. Moreover, silibinin could downregulate JMJD5 and MTA1 in oral cancer. Present study thus identifies that JMJD5 might be an essential prognostic indicator and therapeutic target against OSCC progression. In addition, silibinin is a potential candidate among novel chemotherapeutic agents or adjuvants for modulating JMJD5 in OSCC, through a mechanism likely involving MTA1/JMJD5 axis.

Background Aberrant expression of decoy receptor 3 (DcR3) is considered to be a diagnostic and therapeutic target for human cancers. The aim of this study was to assess DcR3 as a target of the anticancer effects of triptolide (TPL) in preclinical patient‐derived tumor xenograft (PDTX) models of oral squamous cell carcinoma (OSCC). Methods The expression of DcR3 was evaluated through immunohistochemistry, and correlations were examined using clinical variables. The effects of TPL on the expression of DcR3 and cell proliferation were investigated in OSCC cell lines and in PDTX models. Results DcR3 overexpression was associated with overall survival and tumor size. TPL significantly decreased tumor growth. Moreover, TPL inhibited the expression of metastasis‐associated protein 1 (MTA1), a transcription factor for DcR3 in vivo, in vitro, and in PDTX models. Conclusion TPL appeared to exert anticancer effects by repressing DcR3 and MTA1 in vitro, in vivo, and in PDTX models.

Chronic osteomyelitis with proliferative periostitis (Garre’s sclerosing osteomyelitis) is a distinctive type of chronic osteomyelitis that mainly affects children and young adults. Here we report on a 9-year-old girl in whom the condition arose following a pulpoperiapical infection in a mandibular right primary secondary molar. Clinically, it manifested as a bony, hard, mildly tender swelling. Radiography revealed a pathognomonic patchy thickening with radiolucency and radiopacity. The dental inflammation and infection were eliminated and conservative therapy followed. The patient was otherwise asymptomatic. Remission of the disease process and reappearance of a normal-looking mandible was observed with computed tomography imaging, three-dimensional reconstruction and a bone scan at a 10-month follow up visit.

The role of urocortin (UCN) is still ambiguous in human cancers. We tested the hypothesis that using UCN expression discriminates reactive gliosis from primary brain tumors (PBTs). Immunohistochemical analysis of UCN was performed in six reactive gliosis and 99 PBTs. The immunostain scores of UCN were calculated as the degree of intensity multiplied by the percentage of expressed tumor cells. Nuclear staining of UCN revealed weak intensity and small portion of positively stained cells in reactive gliosis. However, comparing with non-neoplastic tissues, higher immunostain scores of UCN were identified in each WHO grade of astrocytomas and meningiomas. Finally, neither WHO grade nor overall survival rate did not significantly correlate with UCN expression in astrocytomas and meningiomas. Our findings demonstrate for the first time that the application of UCN might be a novel biomarker for not only discriminating reactive gliosis from PBTs, but also deciding where the clear surgical margin was.

The interleukin-15 (IL-15) system is important for regulating both innate and adaptive immune responses, however, its role in autoimmune disease remained unclear. Here we found that Il15(-/-) and Il15ra(-/-) mice spontaneously developed late-onset autoimmune phenotypes. CD4(+) T cells of the knockout mice showed elevated autoreactivity as demonstrated by the induction of lymphocyte infiltration in the lacrimal and salivary glands when transferred into nude mice. The antigen-presenting cells in the thymic medullary regions expressed IL-15 and IL-15Rα, whose deficiency resulted in insufficient negative selection and elevated number of natural IL-17A-producing CD4(+) thymocytes. These findings reveal previously unknown functions of the IL-15 system in thymocyte development, and thus a new layer of regulation in T cell-mediated autoimmunity.

Objectives To evaluate whether low body mass index (BMI) is a potential adverse prognostic factor in patients with oral squamous cell carcinoma (OSCC). Material and methods This cross-sectional study included 320 patients with OSCC who underwent therapeutic surgical treatment in Taiwan. The pretreatment BMI was measured as a common indicator of the pretreatment nutritional status to calculate the overall survival in Kaplan-Meier method. The adverse histopathological features of margin status, depth of invasion (DOI), lymphovascular invasion (LVSI), perineural invasion (PNI), and extranodal extension (ENE) were analyzed using the Cox regression model. Results Low BMI (underweight), DOI > 5 mm, and ENE were identified as detrimental prognostic factors. On multivariate Cox regression analysis, the low BMI group (odds ratio [OR] = 1.683; 95% confidence interval [95% CI] 1.116–2.539; P = 0.022), DOI > 5 mm (OR = 2.399; 95% CI 1.459–3.943; P = 0.001), and ENE (OR = 2.467; 95% CI 1.540–3.951; P = 0.000) yielded reduced survival rate. Conclusions The lower BMI had an important and significant effect on the survival of patients with oral cancer and their surgical outcomes. In addition to the adverse histopathological features, a DOI > 5 mm and positive ENE were also identified as the most important prognostic factors. Clinical relevance Underweight patients with low BMI, DOI of > 5 mm, and positive ENE should receive more intensive nutritional supplementation and postoperative adjuvant therapy.

Objectives Lymph node metastasis in oral squamous cell carcinoma (OSCC) is a poor prognostic factor. The histopathologic stage (e.g., pN) is used to evaluate the severity of lymph node metastasis; however, the current staging system insufficiently predicts survival and recurrence. We investigated clinical outcomes and lymph node density (LND) in betel nut-chewing individuals. Material and methods We retrospectively analyzed 389 betel nut-exposed patients with primary OSCC who underwent surgical resection in 2002–2015. The prognostic significance of LND was evaluated by overall survival (OS) and disease-free survival (DFS) using the Kaplan-Meier method. Results Kaplan-Meier analyses showed that the 5-year OS and DFS rates in all patients were 60.9 and 48.9%, respectively. Multivariate analysis showed that variables independently prognostic for OS were aged population (hazard ratio [HR] = 1.6, 95% confidence interval [95% CI] = 1.1–2.5; P = .025), and cell differentiation classification (HR = 2.4, 95% CI = 1.4–4.2; P = .002). In pathologic N-positive patients, a receiver operating characteristic (ROC) curve for OS was used and indicated the best cutoff of 0.05, and the multivariate analysis showed that LND was an independent predictor of OS (HR = 2.2, 95% CI = 1.3–3.7; P = .004). Conclusions Lymph node density, at a cutoff of 0.05, was an independent predictor of OS and DFS. OS and DFS underwent multiple analyses, and LND remained significant. The pathologic N stage had no influence in the OS analysis. Clinical relevance LND is a more reliable predictor of survival in betel nut-chewing patients for further post operation adjuvant treatment, such as reoperation or adjuvant radiotherapy.

Background Biopsy of the retropharyngeal node is not routinely accessible. The diagnosis of retropharyngeal lymph node recurrence in patients with nasopharyngeal carcinoma (NPC) is often based on an imaging study. Methods We reported a patient with NPC who was incorrectly diagnosed with left retropharyngeal lymph node recurrence by both MRI and positron emission tomography (PET)/CT. Results A woman who was treated for stage IVA NPC 2 years previously was found to have a nodal lesion in the left retropharyngeal space on MRI together with focal fluorodeoxyglucose (FDG) uptake on PET/CT. Locoregional recurrence was suspected, and surgery was performed. Subsequent pathology results showed reactive lymphoid hyperplasia. Conclusion Although tissue biopsy for the retropharyngeal node is technically difficult, this case demonstrates that tumor recurrence cannot be diagnosed even based on both positive findings on MRI and PET/CT in patients with NPC. © 2015 Wiley Periodicals, Inc. Head Neck, 2015

Tsai W-C, Lee H-S, Lin C-K, Chen A, Nieh S & Ma H-I (2012) Histopathology 61, 844–856 The association of osteopontin and LMX1A expression with World Health Organization grade in meningiomas and gliomas Aims: Osteopontin (OPN) and LIM homeobox transcription factor 1, alpha (LMX1A) are important factors related to tumour progression, invasion and metastasis in human cancers. The aim of this study was to test the hypothesis that expression of OPN and of LMX1A correlate with the World Health Organization (WHO) grading system of primary brain tumours. Methods and results: Immunohistochemical analyses of OPN and LMX1A expression were performed in 139 cases of brain tumour, including 65 meningiomas, 71 gliomas, and three central neurocytomas. More than 90% of WHO grade I meningiomas showed negative or weak staining for OPN and LMX1A. However, among all WHO grade II and III meningiomas, 100% and 66.7% showed moderate or strong staining for OPN and LMX1A, respectively. Similarly, higher percentages of WHO grade I and II gliomas than of WHO grade III and IV gliomas showed negative or weak staining for OPN. A higher intensity of immunoreactivity for LMX1A correlated with more advanced grade in WHO grade I–III gliomas, but not in WHO grade IV tumours. Conclusions: Higher immunostaining intensity for OPN and LMX1A correlated with WHO grades for meningiomas and some gliomas. Contrary to our expectations, LMX1A staining in WHO grade IV gliomas was shown to be weaker than in WHO grade III tumours.

This study aimed to evaluate the relationship of LMX1A and osteopontin (OPN) expression with clinicopathologic parameters for the 4 most common ovarian surface epithelial carcinomas. Both biomarkers were investigated immunohistochemically using tissue microarrays of 249 specimens including 91 serous cystadenocarcinomas, 56 mucinous cystadenocarcinomas, 64 endometrioid adenocarcinomas, 26 clear cell carcinomas, and 12 normal ovarian tissues. All 4 carcinomas showed significant expression of LMX1A and OPN. In addition, higher immunostaining scores and percentage of cells stained for LMX1A in mucinous cystadenocarcinomas correlated with T stage, American Joint Committee on Cancer clinical stage, poorer tumor differentiation, and poorer survival rate. In serous cystadenocarcinoma, higher percentage of staining for OPN and higher intensity or immunostaining scores for LMX1A correlated with poorer tumor differentiation. Thus, the expression of LMX1A may be an independent prognostic risk factor in mucinous cystadenocarcinoma and a helpful marker in evaluating this tumor's aggressiveness.

Aim: Although the World Health Organization(WHO) histological criteria distinguishing benign fromatypical and malignant meningioma are clear, discern-ing benign from atypical meningioma is still somewhatdifficult, leading to interobserver diagnostic variability.Osteopontin (OPN) and cortactin play important rolesin tumorigenesis, invasion and metastasis of severalhuman cancers. The aim of this study was to evaluatethe usefulness of OPN and cortactin immunohisto-chemistry for distinguishing between benign, atypicaland malignant meningioma and predicting their recur-rence.Methods and results: Seventy-five specimens (48 be-nign, 17 atypical and 10 malignant meningiomas)were investigated immunohistochemically. Themean immunohistochemical scoreimmunohistochemi-cal score ± SE of the mean of both OPN and cortactinwere significantly higher in grade II or grade IIImeningiomas than in grade I meningioma. Discrimi-nant analysis of immunohistochemical OPN expressionshowed correct classification of 97.7% of WHO grade Imeningiomas and 88.2% of WHO grade II meningio-mas (95.4% accuracy). However, the same analysis ofcortactin expression showed correct classification of95.8% of WHO grade I meningiomas and only 23.5%of WHO grade II meningiomas (76.9% accuracy). Acut-off for predicting grades I and II meningiomarecurrence was determined for OPN (3.0) but not forcortactin. Finally, logistic regression identified both thiscut-off (P < 0.05) and WHO grade (P < 0.05) asindependent risk factors for recurrence.Conclusions: OPN expression is a valuable marker fordiagnosis of atypical meningioma and prediction ofgrades I and II meningioma recurrence.Keywords: cortactin, immunohistochemical score, meningioma, osteopontinAbbreviations: DAB, diaminobenzidine; HPF, high-power field; OPN, osteopontin

This study aimed to evaluate the relationship between expression of LGR8, VEGF, MMP-2, MMP-9, fascin-1 and cortactin with clinicopathological parameters in hepatocellular carcinoma (HCC). The six biomarkers were investigated immunohistochemically using tissue microarrays of 93 HCC specimens. The tumor cells showed significant expression of LGR8, VEGF, MMP-9, fascin-1 and cortactin, but not of MMP-2. In addition, higher immunostaining scores for LGR8 in HCC showed negative correlation with T and AJCC clinical stages and upregulation of MMP-9, but no correlation with poorer survival rate; cortactin expression is correlated with poorer tumor differentiation in HCC. Thus, our data suggest that higher expression of LGR8 may facilitate tumor invasiveness in the early clinical stage of hepatocellular carcinoma, and synergic effects of cortactin also play a crucial role in the intrahepatic metastasis. Although tumor biological evidence implicates the relaxin-like hormone family as endocrine mediators of critical cellular action in cancer, characterization of target molecules and signaling pathways specific for LGR8 in defined tumor entities and crosstalk of the relaxin receptors with other receptor systems relevant to carcinogenesis will be of significant clinical relevance and may contribute to novel therapeutic strategies against hepatocellular carcinoma.

Background Patients with hepatocellular carcinoma (HCC) often undergo locoregional therapy before liver transplant either to downstage the tumor or as bridge therapy. Our goal was to assess the risk factors for posttransplant tumor recurrence, specifically the extent of necrosis induced by locoregional therapy.

Prediction of recurrence remains a challenge in histopathological benign/grade I tumors. Osteopontin (OPN) plays important roles in tumorigenesis, invasion, and metastasis of several human cancers. In this study, we investigated OPN protein expression by evaluating the differences between recurrent and non-recurrent histologically benign meningiomas. Thirty-two patients were enrolled, and 23 benign non-recurrent meningiomas and 9 benign recurrent meningiomas were followed for a mean of 34 months after complete surgical resection (Simpson grades I and II). Cytoplasmic OPN staining was evaluated by means of immunohistochemistry (IHC) score and by use of the Allred-8-unit system. We examined clinical biological data, their relationship with tumor recurrence, and the expression of OPN. Our results showed that meningioma recurrence correlated significantly with OPN IHC score (P = 0.001). An OPN Allred score between 0 and 3 was associated with a recurrence-free time of more than 25 months. In comparison, an OPN Allred score from 4 to 8 was indicative of a shorter average recurrence-free time. We concluded that OPN IHC score may play a role in prediction of the recurrence of the grade I meningiomas. Moreover, determination of the OPN Allred score is a reliable, quantitative tool for predicting recurrence-free time in benign meningioma patients.

In addition to its antimicrobial activity, minocycline exerts anti-inflammatory effects in several disease models. However, whether minocycline affects the pathogenesis of inflammatory bowel disease has not been determined. We investigated the effects of minocycline on experimental colitis and its underlying mechanisms. Acute and chronic colitis were induced in mice by treatment with dextran sulfate sodium (DSS) or trinitrobenzene sulfonic acid (TNBS), and the effect of minocycline on colonic injury was assessed clinically and histologically. Prophylactic and therapeutic treatment of mice with minocycline significantly diminished mortality rate and attenuated the severity of DSS-induced acute colitis. Mechanistically, minocycline administration suppressed inducible nitric oxide synthase (iNOS) expression and nitrotyrosine production, inhibited proinflammatory cytokine expression, repressed the elevated mRNA expression of matrix metalloproteinases (MMPs) 2, 3, 9, and 13, diminished the apoptotic index in colonic tissues, and inhibited nitric oxide production in the serum of mice with DSS-induced acute colitis. In DSS-induced chronic colitis, minocycline treatment also reduced body weight loss, improved colonic histology, and blocked expression of iNOS, proinflammatory cytokines, and MMPs from colonic tissues. Similarly, minocycline could ameliorate the severity of TNBS-induced acute colitis in mice by decreasing mortality rate and inhibiting proinflammatory cytokine expression in colonic tissues. These results demonstrate that minocycline protects mice against DSS- and TNBS-induced colitis, probably via inhibition of iNOS and MMP expression in intestinal tissues. Therefore, minocycline is a potential remedy for human inflammatory bowel diseases.

A 58-year-old male patient presented with a recurrent true malignant mixed tumor of the parotid gland. Patchy pulmonary opacities were identified with a chest radiograph. Subsequently, a CT scan of the chest showed pulmonary parenchymal consolidation with amorphous calcifications. This abnormality was confirmed to be the result of a metastatic true malignant mixed tumor by using CT-guided biopsy. The current case demonstrated an extremely rare example of atypical pulmonary metastases from a true malignant mixed tumor of the parotid gland showing an air-space pattern and calcification.

Objective: Survivin and cortactin are factors that promote tumor progression. We tested the hypothesis that survivin and cortactin expressions correlate with the clinico-pathological parameters of colorectal adenocarcinomas and survival time. Methods: Immunohistochemical analysis of survivin and cortactin were performed using tissue microarrays of 119 specimens from 18 well, 50 moderately, and 27 poorly differentiated colorectal adenocarcinomas and 24 colorectal adenomas with dysplasia. As control, 10 specimens of normal colorectal epithelia were included.Results: The percentage of cells immunostained and the immunostaining scores for survivin and cortactin were all significantly higher in well-, moderately, and poorly differentiated colorectal adenocarcinomas than in normal colorectal epithelia. The survivin immunostaining score was significantly correlated with T, M, and AJCC/TNM stages (p `0.05). For cortactin, the score was significantly correlated with T and M stages (p ` 0.05). Higher survivin immunostaining score was associated with higher mortality.Conclusions: Higher expression of survivin and cortactin correlates significantly with tumor stages and shorter survival time. Survivin and cortactin may be good biomarkers of aggressiveness of colorectal adenocarcinomas. Our findings require validation in independent cohorts and these data support the potential targeting of survivin and cortactin for the development of novel therapeutic strategies.

Enterogastric reflux (EGR) is regarded as an unavoidable consequence of distal gastrectomy. We evaluated the efficacy of Roux-en-Y (RY) gastrojejunostomy and Braun enteroenterostomy (BEE) for preventing EGR. Between January 2002 and January 2005, 60 patients who underwent distal gastrectomy for gastric cancer or peptic ulcers were divided into RY, Billroth II reconstruction (BII) without or with BEE (BII+B) according to reconstructive method. After 12 months, EGR and mucosal alterations of the remnant stomach were evaluated using biliary scintigraphy, endoscopy, and histology. Scintigraphy showed fasting and postprandial EGR into the remnant stomach occurred in 5.3% and 21.1% of the RY group, 62.1% and 93.1% of the BII group, and 50.0% and 91.7% of the BII+B group, respectively. Endoscopy showed bile reflux occurred in 15.8% of the RY group, 75.9% of the BII group, and 83.3% of the BII+B group. In addition, the prevalence of Helicobacter pylori (HP) infection in the RY group was less than in the other groups (P

Massive localized lymphedema (MLL) is an uncommon benign skin lesion typically presenting with prominent edema and vascular proliferation in the adipose tissue of lower limbs. When rarely occurring in scrotum, it instead is characterized by a striking proliferation of dermal smooth muscle bundles mimicking acquired smooth muscle hamartoma of dartos. The authors report a rare case of scrotal MLL. A 57-year-old obese man with a history of previous surgery for rectal adenocarcinoma, 20 years earlier, presented with progressive nodular enlargement of the scrotum for 2 years, causing discomfort, difficulty in ambulation, and cosmetic problems. The preoperative radiographic investigation revealed thickening of the scrotal wall with multiple soft-tissue nodules. The patient underwent a wide excision of the scrotal wall, perineum, and penile skin. The pathological examination showed a scrotal MLL associated with well-differentiated squamous cell carcinoma. The authors speculate that prior radiotherapy and surgery together with morbid obesity led to long-standing lymphedema that triggered the proliferation of smooth muscle cells, chronic epidermal change, and finally squamous cell carcinoma.

Objectives Advanced oral cancer is a major public health concern because of a lack of effective prevention and treatment. Triptolide (TPL), a diterpenoid triepoxide derived from the Chinese herb Tripterygium wilfordii, has been demonstrated to possess strong anticancer properties. In this study, we investigated whether TPL exerts anticancer effects on the tumor microenvironment of head and neck squamous cell carcinoma (HNSCC). Materials and methods Human macrophage-like U937 cells were co-inoculated with oral cancer SAS cells in a noncontact transwell coculture system. Cytokine expression was detected using ELISA, and cell proliferation was detected using methylene blue. RNA levels were detected using qPCR. Protein levels were detected using Western blot analysis. In vivo experiments involved using xenografted NOD/SCID mice. Results Our results demonstrated that TPL inhibited the growth of SAS cells co-inoculated with U937 cells in vitro and in vivo. TPL inhibited the invasion, migration ability, and angiogenesis of SAS cells co-inoculated with U937 cells. Expression of cytokines IL-6, IL-8, and TNF-α was induced by co-inoculation, but TPL repressed their expression. Conclusion TPL suppressed the expression of cytokines IL-6, IL-8, and TNF-α, as well as tumor growth, invasion, migration, and angiogenesis in the co-inoculation of human tongue cancer cells with macrophage-like U937 cells. Clinical relevance TPL is a potential candidate among novel chemotherapeutic agents or adjuvants for modulating tumor-associated macrophages in a tumor microenvironment of HNSCC.

Biopsy of the retropharyngeal node is not routinely accessible. The diagnosis of retropharyngeal lymph node recurrence in patients with nasopharyngeal carcinoma (NPC) is often based on an imaging study.We reported a patient with NPC who was incorrectly diagnosed with left retropharyngeal lymph node recurrence by both MRI and positron emission tomography (PET)/CT.A woman who was treated for stage IVA NPC 2 years previously was found to have a nodal lesion in the left retropharyngeal space on MRI together with focal fluorodeoxyglucose (FDG) uptake on PET/CT. Locoregional recurrence was suspected, and surgery was performed. Subsequent pathology results showed reactive lymphoid hyperplasia.Although tissue biopsy for the retropharyngeal node is technically difficult, this case demonstrates that tumor recurrence cannot be diagnosed even based on both positive findings on MRI and PET/CT in patients with NPC.

Limb ischemia/reperfusion (I/R) causes oxidation and inflammation and subsequently induces muscle and kidney injuries. Cepharanthine, a natural plant alkaloid, possesses anti-inflammatory and antioxidative properties. We elucidated the salutary effects of cepharanthine against muscle and kidney injuries following limb I/R. Adult male rats were randomized to receive I/R or I/R plus cepharanthine. I/R was achieved by applying tourniquet high around each thigh for 3 hours followed by reperfusion for 24 hours. Cepharanthine (10 mg/kg, intraperitoneal) was injected immediately before reperfusion. After euthanization, degrees of tissue injury, inflammation, and oxidation were examined. Our data revealed that the I/R group had significant increases in injury biomarker concentrations of muscle (creatine kinase and lactate dehydrogenase) and kidney (creatinine, neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1). Histological assays revealed moderate muscle and kidney injury characteristics in the I/R group. The I/R group also had significant increases in concentrations of inflammatory molecules (interleukin-6, macrophage inflammatory protein-2, and prostaglandin E2) and reactive nitrogen species (nitric oxide) as well as lipid peroxidation (malondialdehyde). Of note, these effects of limb I/R could be mitigated by cepharanthine. These data confirmed that cepharanthine attenuated muscle and kidney injuries induced by limb I/R. The mechanisms may involve its anti-inflammatory and antioxidative capacities.

Primary adrenal lymphoma (PAL) is an extremely rare neoplasm of T-cell origin. Here we describe a 42-year-old woman who suffered from intermittent fevers and night sweats of 3 months duration. Laboratory results, imaging, pathology, and immunohistological examination led to a final diagnosis of primary adrenal T-cell lymphoma (PATL) with adrenal insufficiency. The patient received combination chemotherapy and prednisolone but expired 2 months after the treatment. Most reported PAL patients who have received only one therapeutic modality have unsatisfactory survival rates resulting from tumor recurrence and/or postchemotherapy infections. In contrast, one patient who received an adrenectomy followed by low-dose radiotherapy experienced long-term survival. A combination of therapeutic modalities may improve prognosis for patients with PATL, although the case numbers are too small to draw any conclusions.

Solitary fibrous tumor (SFT) is a benign mensenchymal neoplasm of spindle-cell origin. The authors report the case of a 50-year-old man with SFT arising from the meninges of the left parasellar region with cavernous sinus involvement. The tumor was demonstrated isointense on T1-weighted and heterogeneously hypointense on T2-weighted magnetic resonance imaging (MRI) with strong contrast enhancement. The preoperative MRI diagnosis was meningioma or hemangiopericytoma. Pathological study revealed an SFT that stained positive immunohistochemically for CD34 and vimentin.

AIM To determine whether any markers in biopsy specimens were useful for distinguishing (1) fibroadenoma (FA) from benign phyllodes tumors (PTs); and (2) from benign borderline PTs of the breast. MATERIALS AND METHODS Specimens of 80 breast tumors (20 FA, 38 benign, 12 borderline, and 10 malignant PTs) diagnosed at Tri-Service General Hospital from 1986 to 2006 and 10 normal breast tissue were investigated immunohistochemically for the expression of 11 biomarkers including p53, Ki-67, topoisomerase IIα, p16, retinoblastoma protein (pRb), fascin-1, estrogen receptor-β, CD117, osteopontin, hypoxia-inducible factor-1α, and cyclooxygenase-2. The binary logistic regression method was used to generate functions that discriminate between benign and borderline PT and also between FA and benign PT. RESULTS On the basis of the most active area of stained stromal cells, the staining intensity, and the immunoscore, the expression of Ki-67, topoisomerase IIα, p16, and pRb was significantly higher in borderline or malignant PTs than in benign PTs. Ki-67 could discriminate benign from borderline PTs singly with a high sensitivity (91.7%), specificity (100%), and accuracy (98%). In addition, expression of Ki-67, p16, and pRb was significantly higher in benign PT than in FA. Binary logistic regression identified p16 and pRb as the only marker combination capable of distinguishing FA from benign PTs with sensitivity (94.7%), specificity (75%), and accuracy (87.9%). CONCLUSION Ki-67 may be a useful marker for discriminating benign from borderline PTs, and p16 and pRb may be a useful combination of markers for distinguishing FA from benign PTs in core biopsy specimen.

Osteopontin (OPN) and epidermal growth factor receptor (EGFR) are important factors associated with tumor progression, invasion and metastasis in humans. The aim of this study was to assess the correlation of OPN and EGFR expression with hepatocellular carcinoma (HCC) progression. Expression of OPN and EGFR was assessed by immunohistochemistry in 100 HCC specimens. Immunostaining scores (0 to 400) were calculated from the percentage of cells (0 to 100) at each immunostaining intensity and the immunostaining intensity (0 to 4). The average immunostaining score for OPN was correlated with tumor grade (56.1 for grade I, 104.6 for grade II, and 141.2 for grade III; P = 0.023) and T stage (58.6 for stage T1, 85.9 for stage T2, 126.8 for stage T3, and 189.1 for stage T4; P = 0.029). Similarly, the average immunostaining score for EGFR was correlated with tumor grade (80.5 for grade I, 142.1 for grade II, 230.6 for grade III; P = 0.011) and T stage (96.4 for stage T1, 135.5 for stage T2, 221.3 for stage T3, and 261.4 for stage T4; P = 0.026). In addition, OPN and EGFR immunostaining scores were also correlated with M, N, and AJCC stages. In conclusion, higher expression of OPN and EGFR is significantly associated with advanced histological grades, advanced pathological stages and poorer survival rates in HCC. OPN and EGFR may be used as novel biomarkers for diagnosis or monitoring of progression of hepatocellular carcinoma.

Dysregulation of epidermal growth factor receptor (EGFR) has been associated with colorectal cancer, but no evidence shows a relationship of EGFR expression to clinicopathological parameters in colorectal cancer in Taiwan. Immunohistochemical analysis of EGFR, Ki67, and p53 was performed in tissue microarray slides of 9 normal glandular tissues and 150 specimens including 49 well, 58 moderately, and 43 poorly differentiated colorectal adenocarcinomas. Differences in intensity of EGFR immunostaining and the percentages of Ki67 and p53 positive cells between normal and tumor specimens were evaluated using the Student t-test, one-way ANOVA, and linear regression analysis. Intensity of EGFR staining was weak and nuclear expression of Ki67 and p53 was scattered in all 9 control specimens. Expression of Ki67 and p53 but not EGFR was significantly higher in more advanced grades and TNM stages of colorectal adenocarcinoma than in normal controls. The percentages of Ki67 and p53 stained tumor cells were significantly higher in moderately (Ki67: 60.3 ± 6.5, p53: 47.6 ± 3.8) and poorly (Ki67: 61.8 ± 5.3, p53: 55.1 ± 4.1) differentiated tumor cells than in well differentiated (Ki67: 40.8 ± 4.4, p53: 39.8 ± 4.2) tumor cells. Additionally, the Ki67 and p53 staining intensity was also significantly correlated with the more advanced T, N and American Joint Committee on Cancer (AJCC) clinical stage of colorectal adenocarcinoma, suggesting their usefulness as biomarkers of colorectal adenocarcinoma progression. In conclusion, EGFR immunochemistry may not be a good method for pre-treatment evaluation of colorectal adenocarcinoma in Taiwan.

Introduction: Decoy receptor 3 (DcR3) functions as a death decoy inhibiting apoptosis mediated by the tumor necrosis factor receptor family. It is highly expressed in many tumors and its expression can be regulated by the MAPK/ERK signaling pathway and ERK is a vital member of this pathway. Toll-like receptor 4 (TLR4) is expressed on immune cells. Increased TLR4 expression has been associated with various types of cancers. Material and Methods: The study was conducted to investigate the expression of DcR3, ERK1/2, and TLR4 in astrocytomas and evaluate if they are validating markers for discriminating glioblastoma from anaplastic astrocytoma in limited surgical specimen. Expression of DcR3, ERK1/2, and TLR4 was determined by immunohistochemical staining of tissue microarray from 48 paraffin-embedded tissues. A binary logistic regression method was used to generate functions that discriminate between anaplastic astrocytomas and glioblastomas. Results: The expression of TLR4 and DcR3 was significantly higher in glioblastomas than in anaplastic astrocytomas. DcR3 could discriminate anaplastic astrocytomas from glioblastomas with high sensitivity (93.8%), specificity (90%), and accuracy (92.3%). Conclusion: Our results suggest that DcR3 may be a useful marker for discriminating anaplastic astrocytomas from glioblastomas.

Osteopontin (OPN) and LIM homeobox transcription factor 1, alpha (LMX1A) are important factors related to tumour progression, invasion and metastasis in human cancers. The aim of this study was to test the hypothesis that expression of OPN and of LMX1A correlate with the World Health Organization (WHO) grading system of primary brain tumours.Immunohistochemical analyses of OPN and LMX1A expression were performed in 139 cases of brain tumour, including 65 meningiomas, 71 gliomas, and three central neurocytomas. More than 90% of WHO grade I meningiomas showed negative or weak staining for OPN and LMX1A. However, among all WHO grade II and III meningiomas, 100% and 66.7% showed moderate or strong staining for OPN and LMX1A, respectively. Similarly, higher percentages of WHO grade I and II gliomas than of WHO grade III and IV gliomas showed negative or weak staining for OPN. A higher intensity of immunoreactivity for LMX1A correlated with more advanced grade in WHO grade I-III gliomas, but not in WHO grade IV tumours.Higher immunostaining intensity for OPN and LMX1A correlated with WHO grades for meningiomas and some gliomas. Contrary to our expectations, LMX1A staining in WHO grade IV gliomas was shown to be weaker than in WHO grade III tumours.

Objective Adenoid basal carcinoma (ABC) is an uncommon neoplasm of the uterine cervix. ABC can be accompanied by carcinoma in situ or invasive carcinoma. Most cases are discovered accidentally during radical hysterectomy. ABC is associated with a high risk of human papillomavirus infection (HPV), most often HPV 16 infection. Case report We present a rare case of an 86-year-old Taiwanese married woman who suffered from bloody vaginal discharge and occasional lower abdominal pain and received cervical biopsy. The pathological report revealed squamous cell carcinoma (SCC) of the uterine cervix. After radical hysterectomy, bilateral salpingo-oophorectomy, and bilateral pelvic and para-aortic lymph node dissection, the final pathological report revealed SCC coexisting with ABC, and both of the components were infected by HPV 31. After receiving radiotherapy, she maintained outpatient department follow-up. Conclusion A literature review revealed that this was a rare case of combined ABC–SCC associated with HPV 31 infection. In this case, the ABC component did not affect the tumor stage because it was confined to the cervix. However, we must avoid overestimating the clinical stage because the ABC component is thought to be a benign lesion.

The radiologic appearance of multiple discrete pulmonary nodules in immunocompetent patients, with cryptococcal infection, has been rarely described. We describe a case of pulmonary cryptococcosis, presenting with bilaterally and randomly distributed nodules on a computed tomography, mimicking hematogeneous metastases. Positron emission tomography does not demonstrate 18F-fluorodeoxyglucose (FDG) uptake, suggesting a low probability for malignancy, which is a crucial piece of information for clinicians when making a management decision. We find the absence of FDG uptake correlates with the pathologic finding of an infectious nodule, composed of fibrosis and necrosis. Index terms: Cryptococcosis; Positron emission tomography; Neoplasm metastasis; Multiple pulmonary nodules

Although the World Health Organization (WHO) histological criteria distinguishing benign from atypical and malignant meningioma are clear, discerning benign from atypical meningioma is still somewhat difficult, leading to interobserver diagnostic variability. Osteopontin (OPN) and cortactin play important roles in tumorigenesis, invasion and metastasis of several human cancers. The aim of this study was to evaluate the usefulness of OPN and cortactin immunohistochemistry for distinguishing between benign, atypical and malignant meningioma and predicting their recurrence.Seventy-five specimens (48 benign, 17 atypical and 10 malignant meningiomas) were investigated immunohistochemically. The mean immunohistochemical scoreimmunohistochemical score ± SE of the mean of both OPN and cortactin were significantly higher in grade II or grade III meningiomas than in grade I meningioma. Discriminant analysis of immunohistochemical OPN expression showed correct classification of 97.7% of WHO grade I meningiomas and 88.2% of WHO grade II meningiomas (95.4% accuracy). However, the same analysis of cortactin expression showed correct classification of 95.8% of WHO grade I meningiomas and only 23.5% of WHO grade II meningiomas (76.9% accuracy). A cut-off for predicting grades I and II meningioma recurrence was determined for OPN (3.0) but not for cortactin. Finally, logistic regression identified both this cut-off (P0.05) and WHO grade (P0.05) as independent risk factors for recurrence.OPN expression is a valuable marker for diagnosis of atypical meningioma and prediction of grades I and II meningioma recurrence.

Retroperitoneal malignant germ cell tumors (GCTs) are rare and of uncertain origin. Almost all retroperitoneal GCTs with seminomatous histology have been reported in male patients. Pediatric hypertension in a girl secondary to a retroperitoneal mixed GCT (dysgerminoma plus mature monodermal teratoma) has not been reported previously in the literature. We present the first case of an 11-year-old girl with a retroperitoneal mixed GCT presenting with hypertension.

Cortactin and fascin-1 are important factors affecting progression and metastasis of carcinomas. We tested the hypothesis that cortactin and fascin expression has significant correlation with clinicopathological parameters in pancreatic and ampulla of Vater adenocarcinomas. Immunohistochemical analysis of cortactin and fascin-1 was performed in 50 pancreatic and 40 ampulla of Vater adenocarcinomas. The specimens were from 29 R0, 8 R1, and 13 palliative resections of pancreatic adenocarcinomas and 18 R0, 14 R1, and 8 palliative resections of ampulla of Vater adenocarcinomas. 'R0' resection is defined by complete removal of the tumor and histologically negative surgical margins and 'R1' resection indicates the presence of microscopically residual disease at the surgical margins. The level of expression was assessed by scoring the intensity of cytoplasmic or membranous immunostaining on a 4-point scale. Higher immunostaining scores of cortactin and fascin-1 were both significantly correlated with histological grade, American Joint Committee on Cancer (AJCC) stage, and survival rate in all patients. In conclusion, overexpression of cortactin and fascin-1 implies poorer tumor differentiation, advanced AJCC stage, and shorter survival rate in pancreatic and ampulla of Vater adenocarcinomas.

Triptolide, a diterpenoid triepoxide derived from the Chinese herb Tripterygium wilfordii, exerts an antitumor effect in KB cancer cells through the induction of apoptosis. In this study, we show that triptolide possesses an anticancer effect on drug-sensitive parental KB cells and multidrug-resistant KB-7D and KB-tax cells that overexpress multidrug resistance protein and MDR, respectively. Our data revealed that triptolide decreases the expression of multidrug resistance protein and MDR in both KB-7D and KB-tax cells. It also induces apoptosis in these multidrug-resistant cancer cells by activating caspase-3, and decreasing Mcl-1 and XIAP. Triptolide not only inhibits tumor growth but also induces apoptosis of these drug-resistant cancer cells in xenograft mouse models. Moreover, we also show that triptolide combined with 5-fluorouracil could be an alternative strategy for chemotherapy enhancement. These results indicate the therapeutic value of triptolide on multidrug-resistant cells, and when combined with 5-fluorouracil for the enhancement of cancer therapy.

Small-cell lung cancer accounts for 15-20% of all lung cancers, and it is the cell type most commonly associated with paraneoplastic syndrome. Small-cell lung cancer presenting as ectopic adrenocorticotropic hormone (ACTH) syndrome associated with hypothyroidism and hypogonadotropic hypogonadism is clinically very rare.A 43-year-old man who presented with bilateral lower-extremity edema and hypokalemia had a mass lesion in his left hilum base visible on chest radiograph. Biopsy identified the mass as small-cell lung cancer with focal ACTH staining. The endocrine tests disclosed hypercortisolism, hypogonadism and hypothyroidism.Partial remission as evidenced by regression of the tumor mass and return to normal serum cortisol and ACTH levels occurred after the first course of combination chemotherapy using cisplatin and etoposide. An unexpected left-sided spontaneous pneumothorax developed after the first course of chemotherapy and was treated with thoracostomy and a chest tube. The patient developed persistent air leakage and chronic empyema. The patient received surgery of the Eloesser flap and reconstruction with the latissimus dorsalis flap. The treatment of the complicated problems was successful.Combination chemotherapy may prove effective in the treatment of small-cell lung cancer with ectopic ACTH syndrome, hypothyroidism and hypogonadism.

This study aimed to evaluate the relationship of fascin-1, matrix metalloproteinase (MMP)-2, MMP-9, cortactin, survivin, and epidermal growth factor receptor (EGFR) expression with clinicopathological parameters for the four most common ovarian surface epithelial carcinomas. Six biomarkers were investigated immunohistochemically using tissue microarrays of 185 specimens including 79 serous cystadenocarcinomas, 47 mucinous cystadenocarcinomas, 45 endometrioid adenocarcinomas, and 14 clear cell carcinomas. The four most common ovarian carcinomas showed significant expression of fascin-1, cortactin, survivin, and EGFR, but not of MMP-2 and MMP-9. In addition, higher immunostaining scores for fascin-1 in mucinous cystadenocarcinomas correlated with T stage, N stage, American Joint Committee on Cancer AJCC clinical stage, and a poorer survival rate; for cortactin in serous cystadenocarcinomas correlated with T stage; for cortactin in clear cell carcinomas correlated with T and clinical AJCC stages; and for survivin in clear cell carcinomas correlated with T stage and AJCC clinical stage. In addition, higher immunostaining scores for fascin-1, cortactin, and survivin correlated with poorer tumor differentiation in serous, mucinous, and endometrioid adenocarcinomas. Thus, the expression of fascin-1, cortactin, and survivin may be helpful in evaluating the aggressiveness of ovarian mucinous, serous, and clear cell adenocarcinoma. Additionally, the expression of fascin-1 may be an independent prognostic risk factor in mucinous cystadenocarcinoma.

Cortactin, fascin-1 and EGFR are recognized as important factors in tumor progression. We tested the hypothesis that cortactin, fascin-1 and EGFR expression correlates with clinicopathological parameters of the four most common ovarian surface epithelial carcinomas – serous cystadenocarcinoma, mucinous cystadenocarcinoma, endometrioid adenocarcinoma, and clear cell carcinoma. Immunohistochemical analysis of cortactin, fascin-1 and EGFR was performed using tissue microarrays of 172 specimens comprising 69 serous cystadenocarcinomas, 44 mucinous cystadenocarcinomas, 45 endometrioid adenocarcinomas and 14 clear cell carcinomas. All ovarian carcinomas showed significant expression of cortactin, fascin-1 and EGFR in staining intensity, tumor percentages and immunostaining scores. In addition, higher immunostaining scores of fascin-1 correlated with more advanced cancer stages (TNM), poorer histological differentiation and poorer survival rate of mucinous cystadenocarcinoma. Similarly, higher immunostaining scores of cortactin correlated with T stages and histological differentiation of serous cystadenocarcinoma. The immunostaining scores of EGFR did not correlate with TNM stages, tumor differentiation or prognosis in the four ovarian surface epithelial carcinomas. Our findings suggest that cortactin and fascin-1 may serve as good biomarkers in evaluating aggressiveness of ovarian serous and mucinous cystadenocarcinoma. And the pharmacological inhibitors of fascin-1 activity may slow down tumor progression and prolong survival time in patients with mucinous cystadenocarcinoma.

Adult-onset Still’s disease (AOSD) is an inflammatory disorder characterized by high-spiking fever, arthritis, and an evanescent rash. The pattern of chronic arthritis is a universal feature of AOSD. However, chronic bursitis with the formation of numerous rice bodies is a very rare presentation in a patient with AOSD. To our knowledge, no case of formation of numerous rice bodies in AOSD has been reported thus far. We describe the case of a 28-year-old man with AOSD with rice bodies in his left shoulder joint.

Primary adrenal lymphoma (PAL) is an extremely rare neoplasm of T-cell origin. Here we describe a 42-year-old woman who suffered from intermittent fevers and night sweats of 3 months duration. Laboratory results, imaging, pathology, and immunohistological examination led to a final diagnosis of primary adrenal T-cell lymphoma (PATL) with adrenal insufficiency. The patient received combination chemotherapy and prednisolone but expired 2 months after the treatment. Most reported PAL patients who have received only one therapeutic modality have unsatisfactory survival rates resulting from tumor recurrence and/or postchemotherapy infections. In contrast, one patient who received an adrenectomy followed by low-dose radiotherapy experienced long-term survival. A combination of therapeutic modalities may improve prognosis for patients with PATL, although the case numbers are too small to draw any conclusions.

Kaposi's sarcoma (KS) is the most common AIDS-associated neoplasm. It involves the gastrointestinal tract, skin and lymph nodes with about equal frequency. However, most cases of gastrointestinal KS are clinically silent and found incidentally. We report the case of a 31-year-old homosexual man who developed intussusception in association with a primary ileal KS. He was admitted due to abdominal pain lasting 2 hours. Flat abdominal roentgenogram revealed small bowel ileus in the central abdomen. Abdominal sonography and computerized tomography revealed an intraluminal soft tissue mass in the small intestine with an intussusception. Exploratory laparotomy found an ileal tumor mass 90 cm proximal to the ileocecal valve. Pathologic examination of the resected intestine showed KS. HIV-1 infection was confirmed by Western blot. The CD4 T-cell count was 59/mm3. In conclusion, intussusception by enteric KS may present as the initial AIDS-associated neoplasm in patients with HIV infection.