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We report a patient who developed reactivated toxoplasmic encephalitis due to human immunodeficiency (HIV)-associated immune compromise, resulting in a breakdown of the balance between the host immunity and toxoplasma cyst. Through detailed pathological analysis, spilling of tachyzoites from the ruptured wall of toxoplasma cyst can be identified. It was also proved that Toxoplasma gondii would infect endothelial cells of blood vessels, leading to vasculitis and brain ischemic necrosis. By transmission electron microscope (TEM), apical complex of the parasite can be identified, as well as tachyzoites in rapid reproduction through fission. Rhoptry, a club-shaped specialized organelle, which is characteristic of the motile stages of Apicomplexa protozoans, was also identified. The prevention of toxoplasma infection is still an issue to be emphasized in public health. This article is special in its pathophysiology-based description of the morphology. 'Form ever follows function' is a famous quote from the architect Louis Sullivan. In this case report, we make effort to depict a pathophysiology-based or a 'form-function correlation' interpretation of the histopathological findings by light microscope, IHC and ultrastructural examination. We believe such an approach should also be included in the daily pathology resident training program.

Breast capillary hemangioma is a rare benign vascular tumor. A 59-year-old asymptomatic woman underwent screening mammography and breast ultrasound. B-mode ultrasound revealed a lobulated, hypoechoic mass. Color Doppler ultrasound showed no intratumoral blood flow. Contrast-enhanced ultrasound (CEUS) revealed internal fast homogeneous contrast enhancement of the mass and persistent enhancement after 4 min. A 14-gauge core needle biopsy was then performed. The radiologic and pathologic appearances were concordant with breast capillary hemangioma. The ultrasonic manifestations of breast hemangioma may vary, and differentiation from other inflammatory diseases and malignancies is challenging. CEUS may help in observing the vascular characteristics of breast capillary hemangioma.

Warthin tumor with ulceration of the surrounding skin is extremely rare, making it difficult to differentiate from parotid cancer in the clinical setting. We report a 65-year-old man with a Warthin tumor in the right parotid gland that had ulceration of the overlying skin. The patient presented with right upper neck mass 2 years ago. Ultrasound and fine needle aspiration were done, and Warthin tumor was suspected. One year later, the mass was enlarged with ulceration of the skin. Superficial parotidectomy with fusiform excision of the skin was performed, and histopathological diagnosis revealed a Warthin tumor with inflammatory change. We proposed that this unique manifestation may have been induced by fine needle aspiration, enlargement of the tumor, and ischemic changes secondary to pulmonary arteriovenous malformations.

Background and Objectives: We aimed to assess the diagnostic value of various immunohistochemical (IHC) markers and panels for differentiation among benign follicular nodules (BFNs), noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTPs), noninvasive encapsulated follicular variants of papillary thyroid carcinoma (NEFVPTCs), and infiltrative FVPTC (IFVPTC). Materials and Methods: Sixty-three cases were classified as BFNs, NIFTPs, NEFVPTCs, or IFVPTCs and were evaluated using the following markers: CK19, CD56, galectin-3, CITED1, HBME-1, VE1, and TROP-2. Results: The IHC results for NIFTP and NEFVPTC exhibited no statistically significant differences. In differentiating IFVPTCs from BFNs and NIFTPs/NEFVPTCs, galectin-3 and TROP-2 were the markers with the highest sensitivity plus high specificity, respectively. In various combinations, panel co-expression of two markers, including galectin-3 and/or HBME-1 and/or TROP-2, and the combination of galectin-3 and TROP-2 co-expression could achieve 100% in all aspects. In terms of discrimination of BFNs from NIFTP/NEFVPTC, CK19 was the single most sensitive marker (81.3%), while CD56 was the most specific (100%). The panel consisting of CK19 and/or HBME-1 exhibited the greatest sensitivity (96.9%), but the panel with CD56 and/or HBME-1 exhibited the greatest specificity (90.5%). Conclusions: Our results broaden the use of IHC markers for differential diagnoses among the four groups of follicular-based lesions. In addition, the similar IHC profiles of NIFTP and NEFVPTC also suggest the original criterion of &lt, 1% papillae within tumors, providing a reliable NIFTP diagnosis. Their close relationship may represent a spectrum of progressing neoplasia.

BACKGROUND Buccal mucosal squamous cell carcinoma (BMSCC) is an aggressive oral cancer. Moreover, reversion-inducing cysteine-rich protein with Kazal motifs (RECK) is a well-known tumor suppressor in many cancers. Our aim was to investigate the association of RECK expression with prognosis in BMSCC patients with different clinicopathological features. MATERIALS AND METHODS The expression level of RECK was determined by immunohistochemistry using tissue microarrays containing specimens from 193 BMSCC patients. The association of RECK expression with outcomes in BMSCC patients stratified by different clinicopathological features was analyzed by Cox proportional hazards models. RESULTS The low expression level of RECK was associated with shorter disease-specific survival, especially in patients with age >40 years, moderate or poor cell differentiation, advanced pathological stage, and history of postoperative radiotherapy. However, the low expression level of RECK was not associated with poor disease-free survival, except in BMSCC patients with age ≦40 years, advanced pathological stage and lymph node metastasis. Furthermore, RECK-knockdowned cells showed higher cell viability and abilities of invasion/migration, indicating that RECK might be a tumor suppressor for tumor progression in oral cancer. CONCLUSION The low expression of RECK might be a potential prognostic biomarker for pathological outcome-dependent BMSCC patients.

PACNS has a broad spectrum of clinical manifestations without typical features, and its clinical diagnosis is challenging. We report an elderly patient of cerebellar PACNS (Primary angiitis of central nervous system) presented as a brain tumor by MRI, and primary angiitis was proven by pathology.We report an 81-year-old female who complained about vertigo for 3 weeks with right arm dysmetria. There were no other neurologic symptoms/signs, and the patient was free from headache. Brain CT showed a space-occupying lesion over the right cerebellum, and a high-grade glioma was suspected by brain MRI and MRS. The pathologic result of brain biopsy showed granulomatous variant of PACNS. The patient received immunosuppressant therapy as long-term therapy, and had favorable response during a 2-year follow up.Due to variations in clinical presentation and nonspecific findings on imaging studies, PACNS is not easily diagnosed, especially in the aged population. PACNS should be considered as one of the differential diagnoses of any CNS dysfunction. PACNS is also an exclusionary diagnosis, so although brain biopsy is limited for its low sensitivity, its application is still important to exclude the possibility of other diseases. Although there have been reports of fulminant cases, PACNS can be treated successfully with immunosuppressant as maintaining therapy.

Background Ganglioneuromas (GNs) are composed of mature ganglion cells and Schwann cells with a fibrous stroma; GNs are most often observed in children and young adults. The majority of non-cranial GNs are located in the retroperitoneum and posterior mediastinum. Other reported rare sites include the adrenal gland, small intestine, colon and urinary bladder. However, para-testicular GNs are even more rare. Case presentation Herein, we report the case of a patient with concurrent adrenal GN and thyroid papillary carcinoma who developed paratesticular GN eighteen years later. Conclusions We conclude that there is an association among papillary thyroid carcinoma, GN and MEN2 syndromes. This case report may provide important information for the proposed association. However, further studies are required.

The report describes a 55-year-old woman with postmenopausal abnormal vaginal spotting. PET/CT revealed focal hot F-FDG uptake in the fundus portion of the uterine cavity, and pathology of hysteroscopic dilation and curettage showed endometrioid intraepithelial neoplasia of uterine endometrium, an endometrial precancer. This case points to the significance of F-FDG PET/CT in determining the dilation and curettage site for the postmenopausal women with abnormal vaginal spotting. Increased F-FDG activity in the region of the uterus must be investigated to determine the possibilities of primary malignancies, metastases, and benign diseases.

// Jer-Shyung Huang 1, 2, * , Cheng-Mei Yang 3, 4, * , Jyh-Seng Wang 5 , Huei-Han Liou 6 , I-Chien Hsieh 5 , Guan-Cheng Li 6 , Sin-Jhih Huang 6 , Chih-Wen Shu 6 , Ting-Ying Fu 5 , Yun-Chung Lin 7 , Luo-Ping Ger 6, 8 and Pei-Feng Liu 6, 9 1 Department of Radiology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan 2 National Yang-Ming University School of Medicine, Taipei, Taiwan 3 Department of Stomatology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan 4 Department of Dental Technology, Shu-Zen Junior College of Medicine and Management, Kaohsiung, Taiwan 5 Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan 6 Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan 7 Department of Pathology, China Medical University Hospital, Taichung, Taiwan 8 Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan 9 Department of Optometry, Shu-Zen Junior College of Medicine and Management, Kaohsiung, Taiwan * These authors have contributed equally to this work Correspondence to: Luo-Ping Ger, email: lpger@vghks.gov.tw Pei-Feng Liu, email: pfliu@vghks.gov.tw Keywords: buccal mucosa squamous cell carcinoma, caspase-3, cleaved caspase-3, tumorigenesis, prognosis Received: June 04, 2017 Accepted: July 26, 2017 Published: August 24, 2017 ABSTRACT Buccal mucosa squamous cell carcinoma (BMSCC) is the most common oral cancer in Southeast Asia. Caspase-3, a key molecule in regulating apoptosis, promotes the malignancy of various cancers. However, its role in BMSCC is unknown. Herein, we evaluated the association of caspase-3 expression with tumorigenesis and prognosis in BMSCC patients. Immunohistochemical staining indicated that the expression levels of cleaved caspase-3 ( p

Rationale: Lymphoma with an initial manifestation of ascites and peritoneal invasion is rare. Patient concerns: A 65-year-old woman presented to the emergency department with a 3-week history of abdominal distention, anorexia, and night sweating, and a 2-week history of melena. She was a silent hepatitis B virus carrier. Abdominal ultrasound showed massive ascites without cirrhosis. Abdominal computed tomography revealed ascites, infiltrative peritoneal lesions with omental cake appearance, and lymphadenopathies. Diagnosis: We performed paracentesis and the ascites cytology was obtained. The patient also underwent esophagogastroduodenoscopy, which showed ulcerative tumors in the stomach. Both ascites cytology and pathology of the gastric tumors confirmed the diagnosis of B-cell lymphoma. Interventions: This patient received 7 cycles of chemotherapy. Outcomes: Follow-up imaging studies revealed partial remission of lymphoma, but an enlargement of residual tumors in omentum and mesentery, which resulted in intractable ascites and rapid deterioration of performance status. Despite a change of regimen of chemotherapy, this patient expired 10 months after diagnosis. Lessons: Lymphoma should be one of the differential diagnoses in patients with intractable ascites not attributable to other comorbidities.

Tuberculous aortic aneurysm is an extremely rare disease with a high mortality rate. The clinical features of this condition are highly variable, ranging from asymptomatic with or without constitutional symptoms, abdominal pain to frank rupture, bleeding and shock. We herein report the case of a 56-year-old man with a large tuberculous mycotic aneurysm in the abdominal aorta with an initial presentation of repeated attacks of abdominal pain lasting for several months. Due to the vague nature of the initial symptoms, tuberculous aortic aneurysms may take several months to diagnose. This case highlights the importance of having a high index of suspicion and providing timely surgery for this rare but potentially lethal disease.

Epidemiological studies have reported associations between particulate matter (PM) and cardiovascular effects, and diabetes mellitus (DM) patients might be susceptible to these effects. The chief chronic injuries resulting from DM are small vascular injuries (micro-vascular complications) or large blood vessel injuries (macro-vascular complications). However, toxicological data regarding the effects of PM on DM-related cardiovascular complications is limited. Our objective was to investigate whether subchronic PM exposure alters glucose homeostasis and causes cardiovascular complications in a type 1 DM rat model. We constructed a real world PM2.5 exposure system, the Taipei Air Pollution Exposure System for Health Effects (TAPES), to continuously deliver non-concentrated PM for subchronic exposure. A type 1 DM rat model was induced using streptozotocin. Between December 22, 2009 and April 9, 2010, DM rats were exposed to PM or to filtered air (FA) using TAPES in Taipei, Taiwan, 24h/day, 7days/week, for a total of 16weeks. The average concentrations (mean [SD]) of PM2.5 in the exposure and control chambers of the TAPES were 13.30 [8.65] and 0.13 [0.05]μg/m(3), respectively. Glycated hemoglobin A1c (HbA1c) was significantly elevated after exposure to PM compared with exposure to FA (mean [SD], 7.7% [3.1%] vs. 4.7% [1.0%], P

Exposure to zinc oxide (ZnO) has been linked to adverse health effects, but the renal effects of ZnO nanoparticles (ZnONPs) remain unclear. The objective of this study was to determine the renal toxicity of inhaled ZnONPs. Sprague Dawley (SD) rats were exposed to occupationally relevant levels of 1.1 (low dose) and 4.9 mg/m3 (high dose) ZnONPs or high-efficiency particulate arresting-filtered air (HEPA-FA) via inhalation for 2 weeks. Histopathological examinations of rat kidneys were performed at 24 hours, 7 days, and 1 month after exposure. A significant increase in microscopic inflammatory foci with pronounced periglomerular inflammation and interstitial lymphocytic infiltration was found in rats exposed to low and high doses of ZnONPs compared with rats exposed to HEPA-FA at the three time points following 2 weeks of exposure. Tubulitis featuring lymphocytic infiltrate within the tubular epithelium was found after 24 hours but had disappeared at 7 and 30 days in both the low- and high-dose exposure groups. Our findings demonstrate that inhaled ZnONPs cause sustained renal periglomerular and interstitial inflammation through lymphocytic infiltration. These findings provide histopathological evidence regarding sustained renal inflammation of nanoparticle exposure in rats and may provide some insight into the occupational health effects of ZnONPs on exposed workers.

We report the case of a 68-year-old man with a newly defined rare entity of a peripheral pulmonary tumor, consisting of a nodular papillary lesion with papillary structures containing ciliated columnar and goblet cells, as well as floating tumor cells in the mucin pool. The conspicuous mucin pool was observed to be mimicking colloid adenocarcinoma in a low-power view, particularly in a frozen section slide. We originally reported it as an adenocarcinoma during intraoperative consultation. Immunohistochemically, the tumor cells exhibited a similar immunophenotype to pulmonary adenocarcinoma, except for the presence of focal ciliated and basaloid cells, which we found using CK5/6 and P63 immunostaining. No KRAS or EGFR mutation was found. We revised the diagnosis to that of a ciliated muconodular papillary tumor (CMPT). Four years after a wedge resection, the patient remained free of tumors. Although the malignant potential of CMPT cannot be ignored, a wedge resection with a safe margin might be a treatment option for CMPT patients.

Hyalinizing clear cell carcinoma (HCCC) is a rare malignant salivary gland tumor that was characterized as a distinct entity by Milchgrub et al. in 1994 [1]. It has a slight female predominance with ages ranging from 25 to 87 years (mean, 59.4 years) [2]. Most cases occur in the oral cavity, mainly the palate and tongue [2]. Histologically, HCCC is characterized by the predominance of clear cells embedded in a characteristic dual hyaline and fibrocellular stroma [3]. In 2011, Antonescu et al. [2] identified EWSR1 rearrangements in this tumor, which have been subsequently observed in 82% of cases. This genetic change allows the distinction of HCCC from other salivary gland neoplasms with a clear cell phenotype. Here, we present a typical case of HCCC, which we believe is the first case report from Taiwan.

Objective The present study investigated the relationship between the expression of manganese superoxide dismutase (MnSOD), catalase, glutathione peroxidase (GPx), and myeloperoxidase (MPO) in buccal mucosal squamous cell carcinoma (SCC), and the risk of second primary tumors (SPTs). Study design Immunohistochemistry was performed to examine the expression of MnSOD, GPx, catalase, and MPO in tissue microarray slides of 173 male patients with buccal mucosal SCC who had undergone potentially curative resections. Results Forty-five (26.01%) patients developed SPTs. The prevalent subsites of SPTs were buccal mucosa (48.89%), tongue (13.33%), and lip (11.11%). High expression level of MPO was correlated with an increased risk of SPTs, even after adjustment for development of clinicopathologic parameters (high vs. low expression, adjusted hazard ratio = 3.89; 95% confidence interval, 1.33-11.41; P = .013). Conclusions SPTs are common in male buccal mucosal SCC patients. Higher MPO expression in buccal mucosal SCC is a risk factor for SPTs.

Among enterovirus 71 infections, brainstem encephalitis progressing abruptly to cardiac dysfunction and pulmonary edema causes rapid death within several hours. However, no currently known early indicators and treatments can monitor or prevent the unexpectedly fulminant course. We investigate the possible mechanisms and treatment of fatal enterovirus 71 infections to prevent the abrupt progression to cardiac dysfunction and pulmonary edema by using an animal model.Treatment study.Research laboratory.Sprague-Dawley rats.We microinjected 6-hydroxydopamine or vitamin C into nucleus tractus solitarii of the rat and evaluated the cardiopulmonary changes after treatment with ganglionic blocker.The time course of changes in the heart and lungs of rats with brainstem lesions were investigated. Rats were administered 6-hydroxydopamine to induce brainstem lesions, causing acute hypertension in 10 minutes and acute elevations of catecholamines accompanied by acute cardiac dysfunction and increased strong expressions of connexin 43 gap junction protein in heart and lung specimens by immunohistochemical staining within 3 hours. Severe pulmonary hemorrhagic edema was produced within 6 hours, and the rats expired rapidly within 7 hours. After hexamethonium treatment, it was found that the acute hypertension induced by 6-hydroxydopamine lesions was immediately reversed and the acute high rise of catecholamine serum level was significantly attenuated within 3 hours, accompanied by preserved cardiac output and decreased expressions of connexin 43 in the heart and lungs. No pulmonary edema occurred and the rats survived for more than 14 hours.Early hexamethonium treatment attenuates acute excessive release of catecholamines to prevent cardiac dysfunction and pulmonary edema for increasing survival rate.

Cyclin D1 (CCND1) is an important cell-cycle regulator involved in carcinogenesis and progression of prostate cancer. We tested whether genetic variations within the CCND1 gene are related to clinical outcomes in prostate cancer patients receiving radical prostatectomy.A total of 320 clinical localized prostate cancer patients who underwent radical prostatectomy in Taiwan were prospectively follow-up in this study. A total of 5 tagged single-nucleotide polymorphisms that captured the genetic variability across the CCND1 gene were genotyped, and the prognostic significance on prostate-specific antigen (PSA) recurrence was assessed using the Kaplan-Meier analysis and Cox regression model.We found a polymorphism, rs9344, and 2 haplotypes, GAGG and CTGG, consisting of rs667515, rs2450254, rs9344, and rs678653, were associated with PSA recurrence (P ≤ 0.033). After adjusting for other clinicopathologic predictors, including age, PSA levels, pathologic stage, Gleason score, and surgical margin, rs9344 and the haplotype CTGG remained significant (P ≤ 0.044). The model based on clinical variables plus CCND1 rs9344 or haplotype showed improvement over the model without genetic information, as indicated by ≥ 7.2 % net reclassification improvement (P ≤ 0.040), integrated discrimination index (P ≤ 0.041), and likelihood ratio test (P ≤ 0.028).Our data suggest that the CCND1 rs9344 and a specific haplotype CTGG may be prognostic factors for PSA recurrence after radical prostatectomy.

Objectives This case-control study evaluated the association of the single nucleotide polymorphism rs7372209 (T>C) in pri-mir-26a-1 with the risk and progression of betel quid (BQ)–related oral premalignant lesions (OPLs) and oral squamous cell carcinoma (OSCC). Study Design In total, 597 BQ chewers were recruited: 196 healthy controls, 241 patients with OPLs, and 160 patients with OSCC. Genotypes were determined using the TaqMan real-time assay. Results The C/T + T/T genotypes and T allele in pri-mir-26a-1 were correlated with a decreased risk of BQ-related OPLs (P = .038 and .005, respectively), oral leukoplakia (P = .01 and .001, respectively), and advanced-stage OSCC (P = .021 and .004, respectively). The effects of the C/T + T/T genotypes and T allele on the decreased risk of OPLs were potent in the older age group (both Pinteraction Conclusions BQ chewers carrying the T allele or C/T + T/T genotypes in pri-mir-26a-1 may have a decreased risk of oral leukoplakia, OPLs, and advanced-stage OSCC.

Background Verrucous carcinoma is a non-metastasizing variant of welldifferentiated squamous cell carcinoma, which has been associated with reactive oxygen species generated by betel quid chewing. Salivary antioxidant systems have been suggested to play a protective role in reducing the oxidative damage. Herein, we investigated the difference of the enzymatic antioxidant system expressions in oral verrucous carcinoma and oral squamous cell carcinoma. Methods The enzymatic antioxidant system expressions, including manganese superoxide dismutase, glutathione peroxidase, and catalase were evaluated by immunohistochemistry in a series of 202 surgically resected oral squamous cell carcinoma and 20 oral verrucous carcinoma specimens, using tissue microarray slides. Results The immuno-staining intensities of superoxide dismutase and glutathione peroxidase were strongest in the oral squamous cell carcinoma group than in verrucous carcinoma. The catalase expression showed no difference between different pathological groups. Conclusions The different degrees of superoxide dismutase and glutathione expressions in verrucous carcinoma and squamous cell carcinoma may be helpful for pathologists to differentiate these two entities, especially between oral verrucous carcinoma and well differentiated oral squamous cell carcinoma.

WWOX has been shown to be a candidate tumor suppressor gene in numerous human cancers. The objective of this study is to determine the expression of WWOX in human renal cell carcinoma tumor cells and its possible correlation with clinical outcome.The WWOX protein expressions of human renal cell carcinoma (RCC) tumor and of matched normal renal parenchyma were examined, and its correlation with clinical cancer-specific survival was investigated.Downregulation of WWOX only in clear cell type RCC was demonstrated in our results including immunohistochemistry, Western blot, and RT-PCR assay. For the remnant cell types of RCC, sample sizes were insufficient to draw any conclusion of WWOX protein expression. The decreased expression of WWOX in clear cell RCC tumor compared with matched normal renal parenchyma was also correlated with clinical cancer-specific survival (Kaplan-Meier, p=0.0482).We proved that the expression level of WWOX is downregulated in human clear cell RCC. Moreover, the decreased expression of WWOX in clear cell RCC tumor compared with matched normal renal parenchyma was also correlated with clinical cancer-specific survival. Since clear cell RCC is a special human cancer using unique molecular pathogenesis, further investigation will provide more linking intracellular signaling of WWOX and novel therapeutic targets of human renal cell carcinoma.

Background. We investigated the relationship of the immunohistochemical expression status of manganese superoxide dismutase (MnSOD), catalase, glutathione peroxi- dase (GPx), and myeloperoxidase (MPO) in buccal mucosal squamous cell carcinoma (SCC) with clinicopathologic parame- ters and prognosis. Methods. The expression status of MnSOD, GPx, catalase, and MPO was evaluated by immunohistochemistry in a series of 216 surgically resected buccal mucosal SCC specimens, using tissue microarray slides. Results. MnSOD, GPx, catalase, and MPO were commonly expressed in buccal mucosal SCC. The high expression level of MnSOD was associated with better disease-specific survival (p ¼ .009), especially for patients in moderate or poor cell differentiation (p ¼ .045), pathologic stage I (p ¼ .002) and postoperative radiotherapy (p ¼ .048). The high expres- sion level of GPx was also correlated with better disease-specific survival (p ¼ .042), especially for patients in pathologic stage IV (p ¼ .010) and postoperative radiotherapy (p ¼ .018). Conclusions. MnSOD and GPx are significant prognostic factors for favorable survival in patients with buccal mucosal SCC. V C 2011 Wiley Periodicals, Inc. Head Neck 33: 1606- 1615, 2011

Cases of isolated hepatic tuberculosis (TB) are rare. The diagnosis is often delayed or missed because of nonspecific symptoms and laboratory findings. Besides, the disease is extremely rare even in a country where TB is an alarming public health problem. This report demonstrates the difficulty in correctly diagnosing local hepatic TB. We report the case of a 62-year-old male patient with end-stage renal disease treated with hemodialysis, who developed 2 months of abdominal distension and general anorexia, with hyperechoic hepatic lesions on ultrasound. Computed tomography suspected multiple liver tumors. The liver biopsy finally led to the diagnosis of TB of the liver without other involvements. We conclude that isolated hepatic TB is one of the rare forms of extrapulmonary TB in dialysis patients. A greater awareness of this rare clinical entity may prevent needless surgical interventions.

We report an extremely rare case of bilateral total limbal stem cell deficiency (LSCD) induced by long-term systemic chemotherapy for squamous cell carcinoma of the lung, and the outcomes of bilateral keratolimbal allograft transplantation (KLAT) in such a case. A 34-year-old male patient had underlying disease of squamous cell carcinoma in the right upper lung with extensive mediastinum and lymph node metastasis and received a series of systemic chemotherapy, including a combination of vinorelbine and cisplatin and a combination of gemcitabine, cisplatin, and docetaxel. According to clinical manifestations of ocular surface disorder, pathology findings, and immunostaining of cytokeratin 13 (CK13), LSCD secondary to systemic chemotherapy was diagnosed. KLAT was performed in both eyes. Although graft rejection developed in the right eye, complete re-epithelialization with favorable visual acuity occurred in the left eye 3 years after limbal transplantation.

Context.—Primary cutaneous lymphoma is an uncommon, extranodal lymphoma, and it is usually more indolent with a better prognosis than its histologically similar systemic counterpart is. Objectives.—To illustrate the clinicopathologic features of cutaneous lymphomas in Taiwan and to compare the relative frequencies of subtypes of cutaneous lymphoma among different geographic areas. Design.—A total of 56 patients with cutaneous lymphomas were retrospectively collected and were reclassified according to the 2005 World Health Organization and the European Organization for Research and Treatment of Cancer and the 2008 World Health Organization classifications. The data were compared with those from other studies for different geographic areas. Results.—Thirty-one (55%) tumors were primary cutaneous lymphomas, and twenty-five (45%) tumors were secondary or concurrent cutaneous lymphomas. Among primary cutaneous lymphomas, 23 cases (74%) were T-cell or natural killer–cell lymphomas, and 8 cases (26%) were B-cell lymphomas. The most common types were extranodal natural killer/T-cell lymphoma, nasal type, and primary cutaneous peripheral T-cell lymphoma, unspecified (5 cases each; 16%). In contrast with other primary cutaneous B-cell and T-cell lymphomas, either primary or secondary extranodal cutaneous natural killer/T-cell lymphomas, nasal type, had extremely poor prognoses (1-year overall survival, 0%). Conclusions.—This study showed that the frequency of subtypes of primary cutaneous lymphoma varied in different geographic areas. Compared with the Western countries, there was a higher frequency of extranodal natural killer/T-cell lymphoma, nasal type, and a lower frequency of mycosis fungoides in Taiwan. Extranodal natural killer/T-cell lymphoma, nasal type, also had an extremely poor prognosis compared with other lymphomas.

Extraosseous Ewing sarcoma is now regarded as a member of the Ewing sarcoma/primitive neuroectodermal tumor (PNET) family. It typically involves the soft tissues of the chest wall, pelvis, paravertebral region, abdominal wall, retroperitoneal region and extremities of children, adolescents and young adults, but it seldom occurs in the female genital tract. We report an extremely rare case of retrospective diagnosis of vaginal extraosseous Ewing sarcoma/PNET which metastasized to the right frontoparietal scalp, skull, and dura. Surgical resection, followed by adjuvant radiotherapy and chemotherapy resulted in a favourable clinical outcome. Both the vaginal and head tumors had similar light microscopic features supporting the diagnosis.

Cadmium (Cd 2+ ) is an industrial and environmental metal. The effect of Cd 2+ on intracellular free-Ca 2+ levels ([Ca 2+ ] i ) and viability in Madin Darby canine kidney cells was explored. Cd 2+ increased [Ca 2+ ] i in a concentration-dependent manner with an EC 50 of 85 μM. Cd 2+ -induced Mn 2+ entry demonstrated Ca 2+ influx. Removal of extracellular Ca 2+ decreased the [Ca 2+ ] i signal by 60%. The [Ca 2+ ] i signal was inhibited by La 3+ but not by L-type Ca 2+ channel blockers. In Ca 2+ -free medium, Cd 2+ -induced [Ca 2+ ] i signal was abolished by pre-treatment with 1 μM thapsigargin (an endoplasmic reticulum Ca 2+ pump inhibitor) and 2 μM carbonylcyanide m-chlorophenylhydrazone (CCCP; a mitochondrial uncoupler). Cd 2+ -induced Ca 2+ release was not altered by inhibition of phospholipase C. At concentrations between 10 and 100 μM, Cd 2+ killed cells in a concentration-dependent manner. The cytotoxic effect of 100 μM Cd 2+ was reversed by pre-chelating cytosolic Ca 2+ with BAPTA. Cd 2+ -induced apoptosis was demonstrated by propidium iodide. Collectively, this study shows that Cd 2+ induced a [Ca 2+ ], increase in Madin Darby canine kidney cells via evoking Ca 2+ entry through non-selective Ca 2+ channels, and releasing stored Ca 2+ from endoplasmic reticulum and mitochondria in a phospholipase C-independent manner.

We report a case of nephrotic syndrome and acute renal failure apparently induced by sunitinib. A 67-year-old man with a history of metastatic renal cell carcinoma presented with progressive kidney dysfunction with proteinuria, general edema, and body weight gain of 21 kg after undergoing 3 weeks of sunitinib therapy. The patient had taken no other over-the-counter medications, and all other possible causes of nephrotic syndrome were excluded. The Naranjo Adverse Drug Reaction Probability Scale score for this event was 6, indicating a high probability that the observed presentations were associated with use of the drug. However, despite the discontinuation of sunitinib, his condition deteriorated, and hemodialysis was initiated for respiratory distress. A renal biopsy was performed, which revealed ischemic acute tubular necrosis with minimal change nephropathy. In conclusion, nephrologists and oncologists should be aware that nephrotic syndrome with ischemic acute tubular necrosis is a possible adverse effect of sunitinib. For early diagnosis of this condition and to avoid renal damage, we recommend differential diagnosis of serum creatinine and proteinuria in patients undergoing sunitinib therapy.

Purpose: Evidence is accumulating indicating that chronic inflammation plays an important role in prostate cancer. We investigated the potential prognostic roles of IL-6, IL-8 and IL-10 polymorphisms in clinical localized prostate cancer after radical prostatectomy. Materials and Methods: A total of 116 clinically localized prostate cancer patients undergoing curative radical prostatectomy were included in this study. The IL-6, IL-8 and IL-10 polymorphisms were determined by the TaqMan real-time PCR method. Their prognostic significance on prostate-specific antigen (PSA) recurrence was assessed using Kaplan-Meier analysis and Cox regression model. Results: The IL-6 polymorphism (rs2066992) T/G and G/G genotype cases were associated with a higher percentage of preoperative PSA levels of ≥10 ng/ml; higher risk of positive surgical margin, and higher risk of extraprostatic extension compared to the T/T genotype. The IL-10 polymorphism (rs1800871) A/A genotype was associated with a higher risk of PSA recurrence compared with the A/G + G/G genotypes and significantly poorer PSA-free survival (log-rank test, p = 0.019). After considering other covariates in a Cox proportional hazard model, the IL-10A/A genotype and high Gleason score (8–10) were still independent predictors of poor PSA-free survival. Conclusion: Our results suggest that the IL-10 polymorphism may be a prognostic factor for PSA recurrence after radical prostatectomy.

Introduction: Acceleration on the +G z axis increases pressure in the cardiac chambers. Our research was designed to study whether: 1) such acceleration would impair cardiac function; and 2) a "preconditioning" exposure to +G z would protect the heart from any such effects. Methods: There were 45 male Sprague-Dawley rats that were randomly divided into 3 groups of 15: 1) control without acceleration (CTRL); 2) exposure to 5 min of + 15 G z (EXP); and 3) pretreatment whereby the 5-min exposure was preceded by two exposures of 30 s at + 15 G z (PRE). Within each group of 15, subsets of 7 animals were used to study: 1) echocardiographic heart function or 2) myocardial injury [lactic dehydrogenase (LDH) and malondialdehyde (MDA)], and 1 animal was used to examine the histology of cardiac tissue. Results: Acceleration (EXP) was found to have a significant effect on cardiac function; specifically the early diastolic myocardial velocity (E m ) and systolic myocardial velocity (S m ) in both ventricles decreased in EXP compared to CTRL, while PRE significantly reduced this effect. The systolic mitral annular velocity in the left ventricular lateral wall was significantly less affected in PRE than in EXP (1.99 ± 0.65 vs. 1.2 ± 0.39 cm ·s -1 , P = 0.017). Enzyme levels showed only minor changes. In histology, no neutrophil infiltration was found in three groups. Conclusions: These results suggest that short bouts of acceleration might offer cardiac protection. Confirmation using larger animal models may allow application of the concept to pilots preparing to undertake sustained high G maneuvers and may explain some aspects of the "G layoff" effect.

Pilocytic astrocytomas are found predominantly in the pediatric population; reports of these tumors are extremely rare in adults. We report 2 cases of adult pilocytic astrocytoma with intracranial hemorrhage. A 32-year-old male presented with neck stiffness and severe headache, and a 34-year-old male was referred for headache and double vision. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a well-enhanced and circumscribed cystic hemorrhagic tumor with mural nodule over the cerebral hemisphere region. Perfusion-weighted MRI (PWI) was also performed in both patients. The measured relative cerebral blood volume ratios of the mural nodules in these 2 cases were, respectively, 1.34 and 2.81 when compared with normal white matter. After surgical resection, microscopic examination of the lesions showed pilocytic astrocytomas. Since pilocytic astrocytoma and other cystic tumors with mural nodule (such as hemangioblastoma) have similar findings on conventional CT and MRI, PWI is helpful in the differential diagnosis. The literature on hemorrhagic pilocytic astrocytoma is also reviewed.

We retrospectively studied 19 cases of nasal NK/Tcell lymphoma for various potential prognostic factors and performed real-time quantitative polymerase chain reaction for Epstein-Barr virus (EBV) viral load in tumor tissue. Patients with a low EBV viral load (

Objectives: Cyclins and cyclin-dependent kinase (CDK) complexes have important regulatory roles during cell cycle progression and can be used as prognostic markers in various kinds of malignant tumors. This study investigated the expression of proliferative cell nuclear antigen (PCNA), p53, Rb, p27kip1, and cyclin D1 by immunostains in bladder tumors, especially urothelial papilloma, papillary urothelial neoplasm of low malignant potential, and low and high grade urothelial carcinoma, to see if their expression is associated with classification or grading of the urinary bladder urothelial carcinoma. Method: Nuclear expression of PCNA, p53, Rb, p27kip1, and cyclin D1 was determined immunohistochemically in a series of 89 urinary bladder tumor specimens, including 13 papilloma, 15 urothelial neoplasm of low malignant potential, 17 low grade urothelial carcinoma, and 44 high grade urothelial carcinoma. The results of immunoreactivity were analyzed with respect to the associations with tumor grade. Results: Eighty-two percent (38/45) of the p27kip1 positive tumors were urothelial carcinoma, and the percentage of the p27kip1 positivity was higher with increasing grade of the urothelial carcinoma (P = 0.011). A tendency of higher percentage of positive p53 immunoreactivity was noted in the urothelial carcinoma (P = 0.053). There was no significant difference in cyclinD1, Rb and PCNA expression between benign, low malignant potential and urothelial carcinoma. Conclusion: We first noted an overexpression of p27kip1 in urinary bladder urothelial carcinoma. The result indicates that some urothelial carcinomas may tolerate this inhibitor of cell cycle progression.

The expression of vascular endothelium growth factor (VEGF) has been correlated to the grading and stage of prostate cancers. However, data regarding Taiwanese prostate cancer patients are lacking. The aim of the present study was to examine VEGF expression in our radical prostatectomy specimens. Methods: Fifty-one radical prostatectomy specimens with prostate cancer (15 stage pT2N0, 25 pT3N0, 11 pT2-4 N1) were stained using goat anti-human VEGF polyclonal antibody (AB-293NA; R&D Systems Inc., Minneapolis, MN, USA). The VEGF expression in malignant and nonmalignant prostate tissues was compared. The correlations of VEGF immunoreactivity with Gleason scores and pathologic stages were examined. Mann–Whitney U test was used for comparison of preoperative prostate-specific antigen levels between patients with and without VEGF expression. Results: Positive VEGF staining was observed in 80.4% of malignant epithelia, 39.2% of peritumoral stroma, 68.6% of benign hyperplastic glands, and 25.5% of adjacent stroma. There was no difference in VEGF expression between malignant and nonmalignant areas. Advanced disease had significantly higher frequency of stroma but not epithelium VEGF staining as compared to organ-confined disease (p = 0.002 and p = 0.412, respectively). The Gleason 7 and higher tumors had significantly higher frequency of VEGF staining in stroma but not glandular epithelium (p = 0.041 and p = 0.353, respectively). Tumors with positive epithelium VEGF staining had significantly higher PSA levels (21.3 ± 18.1 vs. 10.8 ± 6.8 ng/mL; p = 0.013). Conclusion: There was no difference in VEGF immunoreactivity between malignant and benign prostatic epithelium in Taiwanese. High Gleason grade tumors and advanced disease had significantly higher frequency of VEGF expression in stroma but not glandular epithelium. Tumors with positive epithelium VEGF staining had significantly higher PSA levels.

Les leiomyosarcomes vasculaires sont extremement rares et representent moins de 2% de l'ensemble des leiomyosarcomes. La frequence de survenue d'un leiomyosarcome au niveau veineux est 5 fois plus importante qu'au niveau arteriel, la moitie d'entre eux etant localises a la veine cave inferieure. Bien que les leiomyosarcomes developpes a partir d'arteres ou de veines volumineuses aient ete largement rapportes, des tumeurs de ce type interessant les vaisseaux peripheriques du membre superieur sont extremement rares. A notre connaissance, les leiomyosarcomes de la veine cephalique au poignet n'ont pas ete precedemment documentes. Nous rapportons un cas de leiomyosarcome de la veine cephalique chez un homme de 63 ans qui s'etait presente avec un œdeme et une sensibilite de la main et de l'avant-bras droits evoluant depuis plus d'un an. Macroscopiquement, une tumeur solitaire, allongee, blanche et ferme a developpement intra-luminal s'infiltrait le long de la paroi vasculaire avec formation de nodules remplissant la lumiere de la veine cephalique et mesurant 11 cm de longueur. L'examen histologique montra un leiomyosarcome vasculaire de grade intermediaire.

Objective The molecular mechanism of major burn-induced gut damage is not clear. This study is to determine whether IkappaB-kinase (IKK)/nuclear factor-kappaB signaling in intestinal mucosa maintains gut function through the regulation of the c-Jun NH2-terminal kinase (JNK) and p38 phosphorylation. Design Prospective, experimental study. Setting Research laboratory at a university hospital. Subjects Thermal injury models in mice. Interventions Conditional intestinal epithelial cell IKKbeta knockout (Vil-Cre/Ikkbeta(F/Delta) mice and control (Ikkbeta(F/Delta) mice were subjected to 30% total body surface area third-degree burn. JNK inhibitor (SP600125) or p38 inhibitor (SB203580) was given to mice immediately after burn injury. Measurements and main results Thermal injury induced a significant increase of intestinal permeability, nuclear factor-kappaB DNA-binding activity, phosphorylated JNK, phosphorylated p38, and caspase 3 expression of intestinal mucosa in Vil-Cre/Ikkbeta(F/Delta) mice compared with those of Ikkbeta(F/Delta) mice. BCL-xL and cellular FLICE inhibitory protein, but not GADD45beta (growth arrest and DNA damage-inducing protein beta), cellular inhibitor of apoptosis 1, Bfl-1, or TRAIL, messenger RNA expression was significantly decreased in Vil-Cre/Ikkbeta(F/Delta) mice compared with that of Ikkbeta(F/Delta) mice. SP600125 decreased intestinal permeability and increased phosphorylated p38 and tumor necrosis factor receptor-associated factor 2 expression of intestinal mucosa in Vil-Cre/Ikkbeta(F/Delta) mice. SB203580 treatment enhanced thermal injury-induced gut damage in Vil-Cre/Ikkbeta(F/Delta) mice. Conclusions Thermal injury induces nuclear factor-kappaB activation of intestinal mucosa and IKK protects intestinal mucosa from thermal injury-induced gut damage. IKK blocks caspase 3 expression by up-regulating BCL-xL and cellular FLICE inhibitory protein expression. IKK inhibits JNK and p38 but not p44/42 phosphorylation of intestinal mucosa. JNK inhibition increases p38 and tumor necrosis factor receptor-associated factor 2 expression and decreases thermal injury-induced gut damage. Taken together with the enhanced thermal injury-induced gut damage by p38 inhibition, we conclude that IKK maintains gut function by inhibiting JNK phosphorylation, which suppresses p38 phosphorylation and induces gut damage.

Objective. The objective of this study was to investigate whether the expression of SKP2 , p27 and phospho- MAPK/ERK1/2 is associated with the progression of human cervical neoplasia. Methods. We performed immunohistochemical detection to stain formalin-fixed paraffin-embedded cervical tissues with anti-SKP2 and anti-p27 monoclonal antibodies and anti-phospho-p42/44 MAPK antibody. The study sample included 23 normal cervical epithelium, 25 low-grade squamous intraepithelial lesion (LSIL), 19 high-grade squamous intraepithelial lesion (HSIL), and 31 squamous cell carcinomas (SCC). In addition, 14 frozen cervical biopsies, including 1 normal, 6 HSIL, 2 adenocarcinoma and 5 SCC, and a human cervical cancer cell line (HeLa), were analyzed the expression levels of mRNA and protein of SKP2 and p27 by RT-PCR and Western blot analysis, respectively. Results. The expression of SKP2 , p27 and phospho- MAPK/ERK1/2 were strongly associated with cervical neoplastic progression ( P P =0.006, P =0.003, respectively; Fisher's Exact Test). In addition, SKP2 expression was positively correlated with phospho-MAPK/ERK1/2 expression (Spearman correlation coefficient=0.480, P =0.0002). The association between SKP2 and phospho-MAPK/ERK1/2 was significant after controlling for the four histologic grades ( P =0.038, Mantel–Haenszel test). Conclusions. These results suggest that expression levels of SKP2, p27 and phospho-MAPK/ERK1/2 may serve as markers for progression in human cervical carcinoma and may also play roles in cervical carcinoma progression and cervical carcinogenesis.