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Cancer of unknown primary site (CUP) presents as metastatic lesions without an identified primary tumor despite extensive evaluation. Because the primary cancer type cannot be determined, there are no standard treatments, leading to challenges in the treatment and suboptimal clinical outcomes. Herein, we report a 59-year-old woman who presented with an enlarged right inguinal lymph node, and the biopsy revealed metastatic adenocarcinoma. Despite a series of treatments including surgery, radiotherapy, and chemotherapy, the disease progressed. After further treatment with combined chemotherapy and immunotherapy, a treatment response was observed. Genomic profiling was done, which identified KRAS G13D and PIK3CA H1047R mutations. She received treatment with the mTOR inhibitor everolimus, and after 2 months, the right inguinal mass continued to regress. This case highlights that CUP remains a diagnostic and therapeutic challenge, representing an urgent and unmet clinical need. However, in the era of precision medicine, the combination of advanced molecular profiling and sophisticated bioinformatic analysis may have the potential to identify druggable targets for tailored and personalized treatment approaches.

Abstract Background Crosstalk between the aryl hydrocarbon receptor (AhR) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling is called the “AhR–Nrf2 gene battery”, which works synergistically in detoxification to support cell survival. Nrf2-dependent phase II gene promoters are controlled by coordinated recruitment of the AhR to adjacent dioxin responsive element (DRE) and Nrf2 recruitment to the antioxidative response element (ARE). The molecular interaction between AhR and Nrf2 members, and the regulation of each target, including phase I and II gene complexes, and their mediators are poorly understood. Methods Knockdown and forced expression of AhR–Nrf2 battery members were used to examine the molecular interactions between the AhR–Nrf2 axis and AhR promoter activation. Sequential immunoprecipitation, chromatin immunoprecipitation, and histology were used to identify each protein complex recruited to their respective cis-elements in the AhR promoter. Actin fiber distribution, cell spreading, and invasion were examined to identify functional differences in the AhR–Jdp2 axis between wild-type and Jdp2 knockout cells. The possible tumorigenic role of Jdp2 in the AhR–Nrf2 axis was examined in mutant Kras-Trp53-driven pancreatic tumors. Results Crosstalk between AhR and Nrf2 was evident at the transcriptional level. The AhR promoter was activated by phase I ligands such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) through the AhR–Jdp2–Nrf2 axis in a time- and spatial transcription-dependent manner. Jdp2 was a bifunctional activator of DRE- and ARE-mediated transcription in response to TCDD. After TCDD exposure, Jdp2 activated the AhR promoter at the DRE and then moved to the ARE where it activated the promoter to increase reactive oxygen species (ROS)-mediated functions such as cell spreading and invasion in normal cells, and cancer regression in mutant Kras-Trp53-driven pancreatic tumor cells. Conclusions Jdp2 plays a critical role in AhR promoter activation through the AhR–Jdp2–Nrf2 axis in a spatiotemporal manner. The AhR functions to maintain ROS balance and cell spreading, invasion, and cancer regression in a mouse model of mutant Kras–Trp53 pancreatic cancer. These findings provide new insights into the roles of Jdp2 in the homeostatic regulation of oxidative stress and in the antioxidation response in detoxification, inflammation, and cancer progression.

Abstract This study trains three machine learning models with varying complexity—Random Forest, Support Vector Machine, and Neural Network—to predict cyclogenesis at a forecast lead time of 24 hr for given tropical disturbances identified by an optimized Kalman Filter algorithm. The overall performance is competent in terms of f1‐scores (∼0.8) compared to previous research of the same kind. An assessment by SHapley Additive exPlanations (SHAP) values reveals that mid‐level (500 hPa) vorticity is the most influential factor in deciding if a tropical disturbance is developing or non‐developing for all three models. Wind shear and tilting are found to hold a certain level of importance as well. These results encourage further experiments that use physical models to explore the dynamical, mid‐level pathway to tropical cyclogenesis. Another usage of SHAP values in this work is to explain how a machine learning model decides if an individual tropical disturbance case will develop, by listing the contribution of each feature to the output genesis probability, illustrated by a case study of Typhoon Halong. This increases the reliability of the machine learning models, and forecasters can take advantage of such information to issue tropical cyclone formation warnings more accurately. Several caveats of the current machine learning application in the studies of tropical cyclogenesis are discussed and can be considered for future research. These can benefit the interpretation and emphasis of certain output fields in the operational dynamical prediction system, which can contribute to more timely cyclogenesis forecasts.

The most common metastatic sites in breast cancer include the liver, bone, the lungs, and the brain. Metastasis to the gastrointestinal system is rare and can occur years after breast cancer diagnosis. This case report features a woman who was diagnosed with infiltrating ductal carcinoma 10 years ago and was discovered to have stomach metastasis this year. Immunohistochemical staining was employed to distinguish the metastasis from primary gastric cancer. This case is presented to raise awareness of the risk of gastric metastasis from breast cancer after years of breast cancer therapy.

Abstract Personalized genetic profiling has focused on improving treatment efficacy and predicting risk stratification by identifying mutated genes and selecting targeted agents according to genetic testing. Therefore, we evaluated the role of genetic profiling and tumor mutation burden (TMB) using next-generation sequencing in patients with head and neck squamous cell carcinoma (HNSC). The relapse mutation signature (RMS) and chromatin remodeling mutation signature (CRMS) were explored to predict the risk of relapse in patients with HNSC treated with concurrent chemoradiotherapy (CCRT) with platinum-based chemotherapy. Patients in the high RMS and CRMS groups showed significantly shorter relapse-free survival than those in the low RMS and CRMS groups, respectively (p

Abstract The idealized Weather Research and Forecasting (WRF) simulations are conducted to investigate tropical cyclone (TC) size and intensity over the Western North Pacific (WNP) over the past decades, as represented by National Centers for Environmental Prediction/National Center for Atmospheric Research (NCEP/NCAR) R-1, European Center for Medium range Weather Forecasting (ECMWF) twentieth century (ERA20C) reanalysis, and National Oceanic and Atmospheric Administration Cooperative Institute for Research in Environmental Sciences 20th Century (CIRES20) Reanalysis V2 data, and under a future climate, as predicted by the Coupled Model Intercomparison Project Phase 5 (CMIP5). Firstly, sensitivity experiments with varying environmental thermodynamic forcing are conducted to examine how thermodynamic conditions affect TC size and intensity. Secondly, distributions of thermodynamic quantities taken from the NCEP/NCAR R-1, ERA20C, CIRES20, and CMIP5 data are used to initialize four more sets of WRF simulations. There is no significant variation in TC size nor intensity over the WNP within the past 90 years based on the idealized downscaling high-resolution WRF model, whereas those simulations initialized based on CMIP5 data show that both the TC size and intensity would increase in the future (2071–2100) of the representative concentration pathway 8.5 (RCP8.5) as compared to those during the current (2010–2040) climate stage of RCP8.5. An explanation for these findings is given by referring to impact of the air–sea thermal disequilibrium and acutely increasing temperature in the TC outflow, while their relation to previous works is also discussed.

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

The treatment of head and neck squamous cell carcinomas (HNSCCs) is multimodal, and chemoradiotherapy (CRT) is a critical component. However, the availability of predictive or prognostic markers in patients with HNSCC is limited. Inflammation is a well-documented factor in cancer, and several parameters have been studied, with the neutrophil-to-lymphocyte ratio (NLR) being the most promising. The NLR is the most extensively researched clinical biomarker in various solid tumors, including HNSCC. In our study, we collected clinical and next-generation sequencing (NGS) data with targeted sequencing information from 107 patients with HNSCC who underwent CRT. The difference in the NLR between the good response group and the poor response group was significant, with more patients having a high NLR in the poor response group. We also examined the genetic alterations linked to the NLR and found a total of 41 associated genes across eight common pathways searched from the KEGG database. The overall mutation rate was low, and there was no significant mutation difference between the low- and high-NLR groups. Using a multivariate binomial generalized linear model, we identified three candidate genes (MAP2K2, MAP2K4, and ABL1) that showed significant results and were used to create a gene mutation score (GMS). Using the NLR-GMS category, we noticed that the high-NLR-GMS group had significantly shorter relapse-free survival compared to the intermediate- or low-NLR-GMS groups.

Rosai–Dorfman disease (RDD) is a rare proliferative histiocytic disorder, often clinically present with massive lymphadenopathy, which typically involves the cervical lymph nodes and is limited to head and neck. It can also be found extranodally, and an unusual site of incidence is the breast. Although it may be a benign disease, it can mimic malignancy based on features of irregularity and lymphadenopathy; thus, the recognition of this condition before any unnecessary therapeutic management is important. A definitive diagnosis is dependent on pathologic proof. This report describes a 26-year-old Asian female with a recurrent RDD, who presents with a firm and visible nodule in the breast and is treated relatively conservatively by local surgery.

Abstract Epstein‐Barr virus (EBV)‐positive B cells have been detected in 66%‐86% of patients with angioimmunoblastic T‐cell lymphoma (AITL). However, it remains controversial whether EBV status has an impact on the survival of patients with AITL. In this study, we aimed to reevaluate the impact of EBV on the clinicopathological characteristics of AITL. In particular, we focused on the impact of EBV in younger patients with AITL. In total, 270 cases of AITL were studied. Epstein‐Barr virus‐positive B cells were detected in 191 (71%) cases (EBER+ group). Among the patients who received anthracycline‐based therapy, the EBER status did not affect the overall survival (OS) or progression‐free survival (PFS). In the younger group of AITL (≤60 years), PFS was significantly worse in the EBER− group compared to the EBER+ group (P = .0013). Furthermore, the multivariate analysis identified EBER‐negative status, thrombocytopenia, and elevated serum IgA level as significant adverse prognostic factors for PFS (P

Abstract Background Primary lymphomas of the gastrointestinal tract are rare, accounting for only 1 to 4% of malignancies arising in the stomach, small intestine, or colon. The stomach is the most common extranodal site of lymphoma and gastric mucosa-associated lymphoid tissue (MALT) lymphoma accounts for 40% of primary gastric lymphoma. Gastric MALT lymphoma reaches its peak incidence between 50 to 60 years of age, therefore, it is rarely encountered in pediatric population. The presenting symptoms of gastric MALT lymphoma are usually nonspecific and primary perforation of gastric MALT lymphoma is uncommon. Case presentation A 12 year-old female presented with iron deficient anemia developed gastric perforation. Emergency laparoscopic repair of the perforation was performed and tissue pathology showed gastric MALT lymphoma infiltration. Helicobacter pylori eradication and radiotherapy were sequentially performed. Complete remission was achieved at two months after radiotherapy. To our best knowledge, she is the youngest patient with gastric MALT lymphoma reported in the literature. Conclusion Iron deficient anemia is a common presenting manifestation of malignancies in adulthood. In pediatric population, iron deficient anemia is usually caused by nutritional deficient or blood loss. In this case report, we present a teenaged female without previous gastric ulcer history who presented with a rare gastric tumor and an uncommon primary perforation. Even if there is an uncertainty about the exact diagnosis prior to the surgery, the strategy of stomach-preserving therapy by laparoscopy for primary perforation was successful and provided a good quality of life.

Esophageal cancer has a dismal prognosis with a five-year survival rate below 20%. Recently, immunotherapy has become a new standard of care for this cancer; therefore, we aimed to examine the programmed death ligand 1 (PD-L1) expression in esophageal squamous cell carcinoma (ESCC) tissues before and after concurrent chemoradiation therapy (CCRT). In total, 64 patients with pre-CCRT ESCC specimens were examined for PD-L1 expression, with twenty-three of them having a partial response (N = 23) or stable disease (N = 1) after CCRT while post-CCRT tissue specimens were collected. All of them were tested for PD-L1 and 15 of them also had CD8 expression in the paired ESCC samples. The prevalence of PD-L1 positivity was 54.7% and we found a trend of decreased PD-L1 expression and increased CD8 positive signal after CCRT. High pre-CCRT PD-L1 H-score in tumors was related to poor prognosis (adjusted hazard ratio = 2.81; p = 0.02), although CD8 signal was not associated with overall survival either in pre- or post-CCRT treatment. In conclusion, we found that PD-L1 expression tended to decrease in CCRT responders and our result supports PD-L1 expression in tumor as a predictor of ESCC prognosis.

Oral squamous cell carcinoma (OSCC) has a high mortality rate (∼50%), and the 5-year overall survival rate is not optimal. Cyto- and histopathological examination of cancer tissues is the main strategy for diagnosis and treatment. In the present study, we aimed to uncover immunohistochemical (IHC) markers for prognosis in Asian OSCC. From the collected 742 synthetic lethal gene pairs (of various cancer types), we first filtered genes relevant to OSCC, performed 29 IHC stains at different cellular portions and combined these IHC stains into 398 distinct pairs. Next, we identified novel IHC prognostic markers in OSCC among Taiwanese population, from the single and paired IHC staining by univariate Cox regression analysis. Increased nuclear expression of RB1 [RB1(N)↑], CDH3(C)↑-STK17A(N)↑ and FLNA(C)↑-KRAS(C)↑were associated with survival, but not independent of tumor stage, where C and N denote cytoplasm and nucleus, respectively. Furthermore, multivariate Cox regression analyses revealed that CSNK1E(C)↓-SHC1(N)↓ (P = 5.9 × 10–5; recommended for clinical use), BRCA1(N)↓-SHC1(N)↓ (P = 0.030), CSNK1E(C)↓-RB1(N)↑ (P = 0.045), [CSNK1E(C)-SHC1(N), FLNA(C)-KRAS(C)] (P = 0.000, rounded to three decimal places) and [BRCA1(N)-SHC1(N), FLNA(C)-KRAS(C)] (P = 0.020) were significant factors of poor prognosis, independent of lymph node metastasis, stage and alcohol consumption. An external dataset from The Cancer Genome Atlas HNSCC cohort confirmed that CDH3↑-STK17A↑ was a significant predictor of poor survival. Our approach identified prognostic markers with components involved in different pathways and revealed IHC marker pairs while neither single IHC was a marker, thus it improved the current state-of-the-art for identification of IHC markers.

Abstract Background Patients with advanced gastric cancer (GC) may ultimately die because GC mostly leads to synchronous or metachronous metastasis. However, colonic metastasis of GC is extremely rare. According to a PubMed search of papers published from May 1968 to March 2017, only 21 patients with GC (10 patients from 10 case reports and 11 patients from a retrospective study) have been found to have colonic metastasis. In this report, we present two cases of synchronous and metachronous colonic metastases of advanced GC. Case presentation Two patients with advanced GC received a diagnosis of colonic metastasis based on colonoscopic findings and computed tomography images, and the diagnosis was confirmed through pathological immunohistochemical analysis. Herein, we describe the management and outcomes of these metastases. Conclusions Submucosal swelling and segmental bowel wall thickening observed through colonoscopy in patients with advanced GC might indicate colonic metastasis.

The aim of this single-center case-control study is to investigate the feasibility and accuracy of oral cancer protein risk stratification (OCPRS) to analyze the risk of cancer progression. All patients diagnosed with oral cancer in Taiwan, between 2012 and 2014, and who underwent surgical intervention were selected for the study. The tissue was further processed for immunohistochemistry (IHC) for 21 target proteins. Analyses were performed using the results of IHC staining, clinicopathological characteristics, and survival outcomes. Novel stratifications with a hierarchical clustering approach and combinations were applied using the Cox proportional hazard regression model. Of the 163 participants recruited, 102 patients were analyzed, and OCPRS successfully identified patients with different progression-free survival (PFS) profiles in high-risk (53 subjects) versus low-risk (49 subjects) groups (p = 0.012). OCPRS was composed of cytoplasmic PLK1, phosphoMet, and SGK2 IHC staining. After controlling for the influence of clinicopathological features, high-risk patients were 2.33 times more likely to experience cancer progression than low-risk patients (p = 0.020). In the multivariate model, patients with extranodal extension (HR = 2.66, p = 0.045) demonstrated a significantly increased risk for disease progression. Risk stratification with OCPRS provided distinct PFS groups for patients with oral cancer after surgical intervention. OCPRS appears suitable for routine clinical use for progression and prognosis estimation.

Retinal perforation with vitreous seeding is an uncommon condition of treatment-naïve choroidal malignant melanoma. We reported a 52-year-old male who had a pigmented tumor protruding from choroid of his right eye. He had only black shadow sensation for 4 months then a rapid deterioration of vision. Fundus examination showed vitreous haze with many pigmented materials. B-scan ultrasonography revealed a mass with low internal reflectivity and vitreous opacity. The eyeball was enucleated and a stage IIIA melanoma was confirmed by the pathologist. No local recurrences or metastases were found during 31-month follow-up. Although vitreous seeding may indicate rapid tumor growth, early enucleation may insure a better prognosis.

Arsenic is a well-known toxic element and carcinogenic agent. The aim of this study was to investigate p63, E-cadherin, and β-catenin proteins in urothelial carcinoma (UC) in both arsenic contaminated areas [so-called blackfoot disease (BFD) area] and non-BFD areas. The expressions of p63, E-cadherin, and β-catenin proteins in 20 UC cases of blackfoot disease and 22 UC cases in non-BFD areas were detected using immunohistochemical methods. The results revealed a high p63 expression in 20 (47.6%) UC cases and high E-cadherin expression in six (14.3%) UC cases. Expressions of p63 and E-cadherin showed no significant correlations with clinicopathologic parameters. However, all 20 BFD cases and 12 of 22 (54.5%) non-BFD cases showed aberrant β-catenin expression. Ten out of 22 (45.5%) non-BFD cases also had normal membranous immunoreactivity. The β-catenin staining pattern significantly differed between cases in endemic and nonendemic areas of BFD (p=0.001). Tumor sites also significantly correlated with β-catenin expression (p=0.044). In addition, membranous localization of β-catenin was lower in UC from BFD-endemic areas compared with those from non-BFD endemic areas. In conclusion, it is suggested that relocalization of β-catenin from membrane to cytoplasm may be involved in the tumorigenesis of UC from BFD-endemic areas.

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

Hepatocellular carcinoma (HCC) is a primary malignancy of the liver. Patients with HCC usually have poor prognosis and high mortality. It has been shown that carcinoembryonic antigen-related cell adhesion molecule 1 (CD66a) regulates cell signaling, proliferation, and tumor growth. The aim of this study is to analyze the expression and possible role of CD66a in HCC. Immunohistochemical staining of CD66a was performed on 86 HCC cases, and microvessel density was evaluated by CD34 immunostaining. The results were further correlated with clinicopathological parameters. For 47 of 86 HCC cases, the CD66a expression showed diffuse membrane or cytoplasmic staining. The other 39 HCC cases revealed loss of CD66a expression. Loss of CD66a expression was statistically significantly associated with large tumor size (p=0.016), fatty change (p=0.039), patients with transcatheter arterial embolization (p=0.007), and high microvessel density (p=0.036). CD34 expression had no significant association with tumor size, virus infection, histological grade, and capsular invasion. The diffuse and cytoplasmic expression of CD66a may involve the early stage of the HCC, and the loss of CD66a expression indicates tumor progression.

We used satellite data, typhoon-resolving atmospheric forcing and a data assimilating ocean model, the East Asian Seas Nowcast/Forecast System (EASNFS), to investigate circulation and three upwelling regions perturbed by tides and Typhoon Fanapi (2010) in the seas around Taiwan. The three upwelling areas located off northeast Taiwan, off southeast China and over the Penghu Channel off southwest Taiwan are normally limited in expanse before Fanapi. The tidal currents enhance all three. To cope with typhoon strength atmospheric forcing, we applied typhoon-resolving Weather Research and Forecasting (WRF) model wind fields that significantly enhanced Fanapi-induced upwelling. Approaching Taiwan, Fanapi induces a cold wake spreading preferably on the right side of the essentially westward running track in the western Pacific. The three upwelling areas in the East China Sea and Taiwan Strait subsequently become expansive as Fanapi approaches and enters the Taiwan Strait. The mechanisms leading to normal or Fanapi-perturbed upwelling and circulation in seas around Taiwan, especially the latter two mentioned above, are suggested. In essence, Fanapi disrupts circulation in the Taiwan Strait, and also the Taiwan Strait outflow entering the East China Sea, leading to expanded upwelling areas. We also suggest that high-resolution wind and tides application is essential for the upwelling modeling study and also the general circulation in the region with and without typhoons.

Microtubules are an ideal target for anticancer drugs because of their essential role in mitosis. Colchicine is a microtubule destabilizer. Whether the clinically acceptable colchicine concentrations had anticancer effects on human cholangiocarcinoma cells was investigated. Two human cholangiocarcinoma cell lines (C14/KMUH, C51/KMUH) were investigated using clinically acceptable plasma colchicine concentrations (2 ng/mL and 6 ng/mL for the in vitro experiment, 0.07 mg colchicine/kg/d × 14 days for the nude mouse experiment). Our results showed that colchicine caused significantly dose-dependent antiproliferative effects on both cell lines (all p

The association of the tuberous sclerosis complex with angiomyolipoma (AML) arising from the retroperitoneum and mediastinum has not been reported in the literature. We present the first case in which a patient presented with a combined retroperitoneal extrarenal and posterior mediastinal AML. Interestingly, the ipsilateral retroperitoneal AML emerged 15 years after radical nephrectomy for the left renal AML.

Expressions of human p16 and p27 were tested for correlations with clinicopathologic features of urothelial carcinoma (UC). Tissue microarrays (TMA) constructed from paraffin-embedded specimens from 78 patients with UC were analyzed by immunohistochemical staining. In 49 of the 78 tumors (63%), high p16 expression was associated with absence of tumor invasiveness and low-grade carcinoma (p = 0.003 and p = 0.046, respectively). The p27 expression was high in 33 of the 78 tumors (42%) and showed a significant negative association with invasiveness, carcinoma grade, and tumor size (p = 0.016, p = 0.046, and p = 0.014, respectively). Kaplan–Meier analysis indicated that patients with high p27 levels had longer than average overall survival (p = 0.021). This study demonstrates that p16 and p27 are prognostic indicators of tumor stage and grade in UC and that they provide clinicians with the ancillary information needed for selecting suitable therapeutic strategies.

Prostate cancer typically metastasizes to bones and regional lymph nodes. Generalized lymphadenopathy is a rare manifestation of metastatic prostate cancer. We report a case of prostate cancer in a 65-year-old male with initial presentation of generalized lymphadenopathy and no urinary symptoms. Lymph node biopsy revealed metastatic adenocarcinoma, and immunohistochemical staining was positive for prostate-specific antigen (PSA) compatible with a prostatic origin. Directed biopsy confirmed that the tumor originated in the prostate. Therefore, the prostate should be considered a possible origin of metastatic adenocarcinoma in men, and presentations consistent with generalized lymphadenopathy cannot exclude a diagnosis of prostate cancer.

We report the case of a 38-year-old man who developed vanishing bile duct syndrome in association with Hodgkin's lymphoma. He was noted to have cervical lymphadenopathy and marked elevation of total serum bilirubin at diagnosis. He achieved complete remission with normalization of serum bilirubin after eight courses of Adriamycin, bleomycin, vinblastine, and dacarbazine chemotherapy followed with autologous hematopoietic cell transplantation. Consecutive liver biopsies performed at diagnosis and at the stage of complete remission revealed the disappearance and regeneration of interlobular bile ducts, respectively. Our case provides pathological evidence that Hodgkin's lymphoma-related vanishing bile duct syndrome is a reversible bile duct injury disease. Bilirubin is a reliable serum marker to monitor the treatment response of these cases. The mechanism to develop hyperbilirubinemia with vanishing bile duct in such a case of Hodgkin's lymphoma remains to be studied. A literature review was carried out.

This study aims to explore whether certain occupations were associated with the risk of esophageal squamous cell carcinoma (ESCC) in Taiwan. In a hospital-based case-control study, we collected 326 newly diagnosed ESCC patients and 386 age-matched controls (the ratio of case patients: controls = 1:1–2). All respondents completed a questionnaire, including 33 occupations in which environments potential exposure to cancer-related hazards are present. Workers with dust and metal exposure were categorized into Groups A and B, respectively. Relative risks for ESCC were estimated by odds ratios adjusting for covariates (AOR). Compared with the controls, farmer/gardener (AOR = 2.08, 95% CI = 1.02–4.24) and workers in Group A (AOR = 2.80, 95% CI = 1.21–6.47) had significantly higher risk for developing ESCC. A tendency of increased risk was also found in workers in group B (OR = 5.72 95% CI = 2.33–14.03), but such association was not significant after adjusting for other covariates (AOR = 1.57, 95% CI = 0.54–6.61). Our results suggested that farmer/gardener and workers with exposure to dust had a significant excess risk of ESCC. This study added further evidence to the current knowledge that occupational hazards are important in the development of ESCC.

Dermatofibroma (DF) and dermatofibrosarcoma protuberans (DFSP) are the spindle cell mesenchymal neoplasms of the dermis and subcutis. Their histogenesis still remains uncertain and controversial. Traditionally, CD34 and factor XIIIa or other markers have been widely used to distinguish these two diseases. However, the results of these markers reveal overlapping and they lack specificity. Formalin-fixed, paraffin-embedded blocks were collected from the biopsied cases in Kaohsiung Medical University Hospital in Taiwan between 2004 and 2006. This study included 19 cases of DF and 17 cases of DFSP. Immunohistochemical analysis using antibodies CD34, matrix metalloproteinases (MMP)-2, MMP-9, and MMP-11 was performed. We found that the expression of CD34, MMP-2 and MMP-11 shows significant statistical differences in Immunohistochemistry (IHC) study positive or negative reactivity (positive of CD34 in DFSP and positive of MMP-2 and MMP-11 in DF; p=0.03, p

During August and September 2008, The Observing System Research and Predictability Experiment (THORPEX) – Pacific Asian Regional Campaign (T-PARC) was conducted to investigate the formation, structure, targeted observation, extratropical transition (ET) and downstream effects of tropical cyclones (TCs) in the Western North Pacific (WNP) region. This study investigates the effect of targeted dropsonde observations from T-PARC and the TC best track data on the track forecast of Typhoon Sinlaku (2008). A WRF-based ensemble Kalman filter (EnKF) is used for a series of observation system experiments (OSEs). From the innovation statistics and rank histograms, the EnKF behaves well in terms of ensemble spread, despite some spread deficiency in low-tropospheric winds and warm and moist biases. Assimilation of targeted dropsonde observations leads to improved initial position and subsequent track forecast compared with experiments that only assimilate conventional observations. In the meantime, assimilation of TC position reduces the initial position error, whereas assimilation of minimum sea level pressure (SLP) information is efficient to analyse the strong vortex structures of TC and reduces track forecast errors. Assimilation of TC position and minimum SLP information is particularly beneficial when dropsonde observations do not exist.

Pheochromocytomas and paragangliomas (extra-adrenal pheochromocytomas) are catecholamine-secreting tumors. The paraganglioma of the urinary bladder is an uncommon neoplasm with a higher malignancy rate. Only about 60% of bladder paragangliomas presented with hematuria, and most of them were microscopic hematuria. Herein, we report two cases of bladder paraganglioma with bladder bloody tamponade. In Case 1, radical cystectomy and regional lymphadenectomy were performed for a huge bladder tumor and left pelvic lymph nodes metastasized. In Case 2, we chose endoscopic transurethral resection of the bladder tumor. Literatures since 1989 were also reviewed to illustrate the clinical characteristics and current treatments.

In this study, we investigated the expression of phosphorylated signal transducer and activator of transcription 3 (p-STAT3) Tyr705 and suppressor of cytokine signaling 3 (SOCS3) in urothelial carcinoma (UC). p-STAT3 (Tyr705) and SOCS3 were analyzed by immunohistochemistry using tissue microarray and Western blotting. Our results showed that p-STAT3 (Tyr705) was frequently detected in high-grade and infiltrating UC. However, there was no difference in p-STAT3 (Tyr705) staining between UC of the upper and lower urinary tracts. In addition, there was no significant correlation between expression of SOCS3 and histological differentiation and invasiveness of UC. These findings suggest that overexpression of p-STAT3 (Tyr705) occurs in UC, and that pathways other than SOCS3 may contribute to its activation in this cancer.

Low-grade fibromyxoid sarcoma (LGFMS) is a rare neoplasm that commonly arises in the deep soft tissues of the lower extremities, particularly in the thigh. LGFMS occurs preferentially in young male adults. The microscopic appearance of LGFMS exhibits bland fibroblastic spindle cells with a whorled or linear arrangement in fibrous and myxoid areas. Although LGFMS has a deceptively benign histologic appearance, local recurrence and late metastases have frequently been reported. Diagnosis of LGFMS is still difficult because of its characteristic bland-looking histologic features that can be confused with other benign or low-grade fibromyxoid lesions. Although immunohistochemical staining can offer an overview of the differential diagnosis of myxoid tumors of soft tissue, it is sometimes limited for diagnosis of LGFMS. However, recent cytogenetic and molecular analyses have provided significant improvements in the diagnosis of LGFMS. Such analyses have demonstrated that most cases of LGFMS have a characteristic t (7,16) (q33;p11) translocation, resulting in the FUS-CREB3L2 fusion gene. We report a 29-year-old female who presented with a LGFMS located in the soleus muscle of her left lower leg. Preoperative imaging suggested the possibility of an intramuscular histiocytoma of the left soleus muscle. In conclusion, diagnosis of LGFMS can be challenging in routine practice in surgical pathology because of its bland-looking features. The immunohistochemical and ultrastructural findings were consistent with the fibroblastic properties of LGFMS. Cytogenetic and/or molecular genetic analyses can be used as ancillary diagnostic tools for LGFMS.

Classical renal angiomyolipoma (AML) is a common tumor that, in most cases, follows a benign course and has clearly defined radiologic and histological characteristics. However, rare cases of clinically aggressive or malignant AML, the epithelioid variant of AML (EAML), have been reported. Here, we review the five cases of EAML diagnosed since 2000 at our institution to highlight the spectrum of clinical, radiological and histological characteristics. In all cases, renal lesions seen on computed tomography (CT) were considered as suspicious for renal cell carcinoma (RCC) without tumor extension or metastasis. One of the two patients with definitive tuberous sclerosis complex had a small conventional AML with fat content in the other kidney. Histologically, these tumors can resemble sarcomatoid RCC or high grade RCC. The final diagnosis is established by the presence of perivascular epithelioid cells and immunohistochemistry markers. There was no evidence of local recurrence or metastatic disease found by sonography, CT and magnetic resonance imaging during the follow-up period. EAMLs are capable of aggressive or malignant clinical behavior. Approximately one third of the reported EAMLs show advanced disease; therefore, we recommend that it is important to treat and closely follow-up such cases, similar to that for RCC, because of its malignant potential.

Intranasal or paranasal sinus olfactory neuroblastoma is a rare malignant neoplasm of olfactory neuroepithelial origin, accounting for approximately 5% of paranasal sinus cancers. Most of the presenting symptoms include nasal obstruction, nasal bleeding, anosmia, rhinorrhea, and headache. In this present report, we describe a 79-year-old man who presented with bilateral nasal congestion for more than 1 year. Nasoendoscopy showed a huge, smooth, mucosal tumor in the nasopharynx with extension to the posterior nasal septum. The tumor was completely resected under endonasal endoscopy and the pathology revealed olfactory neuroblastoma. Olfactory neuroblastomas usually arise in the cribriform plate and superior turbinate. However, the origin and isolation of olfactory neuroblastomas to the sphenoid sinus is exceedingly rare. Only four cases of olfactory neuroblastoma isolated in the sphenoid sinus have been described in English literature and the frequency of presenting symptoms with cranial neuropathies and headache. We report a case of primary sphenoid sinus olfactory neuroblastoma with the greatest enlargement reported to date.

Diagnosis of abdominal splenosis is often undiagnosed until treatment for splenic rupture or splenectomy. This report describes a patient with splenosis mimicking hepatic tumor. The patient had a history of splenic trauma with splenectomy and chronic hepatitis C. After routine abdominal ultrasound revealed a liver nodule, further imaging studies, including magnetic resonance imaging, computed tomography and angiography, were performed. After the patient eventually underwent surgery, pathology revealed splenic tissue. Despite its distinguishable clinical features, splenosis is difficult to identify by modern imaging modalities. Therefore, accurate and timely diagnosis of this disease requires constant vigilance.

Rhabdomyosarcoma (RMS) is the most common soft tissue tumor of childhood; about 80% of cases occur before the age of 21 with the remaining 20% evenly spread throughout the remaining decades. A primary paratesticular site is considered to have a good prognosis in comparison with other RMS sites. Histologically, any subtype of RMS, including alveolar, pleomorphic, embryonal, and mixed type, may occur in the paratesticular region, but only a relatively small number of cases are mixed and this variant has a poor prognosis. We report a case of paratesticular RMS (mixed embryonal and alveolar type) in a 16-year-old boy.

Background. The suppression of Helicobacter pylori (H. pylori) decreases H. pylori-related diseases. The probiotics have an inhibitory effect on H. pylori. Aim. We investigated the effects of long-term use of yogurt on H. pylori based on Mongolian gerbils’ model. Materials and Methods. Yogurt (containing a supplement of Lactobacillus acidophilus, Bifidobacterium lactis, etc.) was used. Forty-six gerbils were divided into five groups. All groups were inoculated with H. pylori for 5 to 8 weeks. The yogurt was given as follows: Group (Gr.) A: from 1st to 4th week; Gr. B from 5th to 8th week; Gr. C: from 17th week to sacrifice; Gr. D: from 5th week to sacrifice. Gerbils were sacrificed on the 52nd week. Histology was evaluated according to the Sydney system. Results. The positive rates of H. pylori were 60% (Gr. A), 75% (Gr. B), 67% (Gr. C), 44% (Gr. D), and 100% (Gr. E). Gr. D showed lower inflammatory score. Only Gr. E (60%) had intestinal metaplasia. Gr. D showed higher IL-10 and lower TNF-α expression than Gr. E. Conclusion. Long-term intake of yogurt could decrease H. pylori infection. The long-term use of yogurt would be an alternative strategy to manage H. pylori infection.

Esophageal squamous cell cancer (ESCC) is one of the most common fatal human cancers. The identification of biomarkers for early detection could be a promising strategy to decrease mortality. Previous studies utilized microarray techniques to identify more than one hundred genes; however, it is desirable to identify a small set of biomarkers for clinical use. This study proposes a sequential forward feature selection algorithm to design decision tree models for discriminating ESCC from normal tissues. Two potential biomarkers of RUVBL1 and CNIH were identified and validated based on two public available microarray datasets. To test the discrimination ability of the two biomarkers, 17 pairs of expression profiles of ESCC and normal tissues from Taiwanese male patients were measured by using microarray techniques. The classification accuracies of the two biomarkers in all three datasets were higher than 90%. Interpretable decision tree models were constructed to analyze expression patterns of the two biomarkers. RUVBL1 was consistently overexpressed in all three datasets, although we found inconsistent CNIH expression possibly affected by the diverse major risk factors for ESCC across different areas.

BACKGROUND:Few studies have reported the association between lifestyle factors and prognosis of esophageal squamous cell carcinoma (ESCC) and among these, the effects of habitual areca nut chewing have never been examined. METHODOLOGY/PRINCIPAL FINDINGS:Data from 718 pathology-proven ESCC patients recruited in a multicenter hospital-based case-control study between 2000 and 2008 in Taiwan were analyzed. Clinical and lifestyle information were obtained by chart review and questionnaire survey. Death was confirmed using the National Death Index. The mean age at diagnosis was 59.8 years and 506 (70.5%) patients presented with stage III or IV diseases. The overall 1- and 5-year survival rates were 41.8% and 9.75% respectively. In addition to clinical stage, habitual alcohol drinking was found to be the strongest predictor for ESCC survival, followed by areca chewing and smoking. Compared with non-users, patients who regularly used all three substances (alcohol, areca nut, and cigarette) had 1.52 times the risk of early death (adjusted hazard ratio = 1.52, 95% CI = 1.02-2.27, p = 0.04). In addition, the more the number of substances used, the worse the prognosis of ESCC (adjusted p for trend = 0.01). CONCLUSIONS/SIGNIFICANCE:Our study found that indulgence in more substances is a significant predictor of ESCC survival. Further mechanistic studies are necessary to elucidate how these substances lead to an adverse outcome.

BACKGROUND: The epidemiology of neuroendocrine tumors (NETs) is not well illustrated, particularly for Asian countries. METHODS: The age-standardized incidence rates and observed survival rates of NETs diagnosed in Taiwan from January 1, 1996 to December 31, 2008 were calculated using data of the Taiwan Cancer Registry (TCR) and compared to those of the Norwegian Registry of Cancer (NRC) and the US Surveillance, Epidemiology, and End Results (SEER) program. RESULTS: During the study period, a total of 2,187 NET cases were diagnosed in Taiwan, with 62% males and a mean age of 57.9 years-old. The age-standardized incidence rate of NETs increased from 0.30 per 100,000 in 1996 to 1.51 per 100,000 in 2008. The most common primary sites were rectum (25.4%), lung and bronchus (20%) and stomach (7.4%). The 5-year observed survival was 50.4% for all NETs (43.4% for men and 61.8% for women, P

BACKGROUND: Second cancers have been reported to occur in 10-20% of patients with neuroendocrine tumors (NETs). However, most published studies used data from a single institution or focused only on specific sites of NETs. In addition, most of these studies included second cancers diagnosed concurrently with NETs, making it difficult to assess the temporality and determine the exact incidence of second cancers. In this nationwide population-based study, we used data recorded by the Taiwan Cancer Registry (TCR) to analyze the incidence and distribution of second cancers after the diagnosis of NETs. METHODS: NET cases diagnosed from January 1, 1996 to December 31, 2006 were identified from the TCR. The data on the occurrence of second cancers were ascertained up to December 31, 2008. Standardized incidence ratios (SIRs) of second cancers were calculated based on the cancer incidence rates of the general population. Cox-proportional hazards regression analysis was performed to estimate the hazard ratio (HR) and 95% confidence interval (CI) for the risk of second cancers associated with sex, age, and primary NET sites. RESULTS: A total of 1,350 newly diagnosed NET cases were identified according to the selection criteria. Among the 1,350 NET patients, 49 (3.63%) developed a second cancer >3 months after the diagnosis of NET. The risk of second cancer following NETs was increased compared to the general population (SIR = 1.48, 95% CI: 1.09-1.96), especially among those diagnosed at age 70 or older (HR = 5.08, 95% CI = 1.69-15.22). There appeared to be no preference of second cancer type according to the primary sites of NETs. CONCLUSIONS: Our study showed that the risk of second cancer following NETs is increased, especially among those diagnosed at age 70 or older. Close monitoring for the occurrence of second cancers after the diagnosis of NETs is warranted.

Whether the habitual use of substances (tobacco, alcohol, or areca nut (seed of the Areca palm)) can affect the age of esophageal squamous cell carcinoma (ESCC) presentation has rarely been examined.The study subjects were those who were males and the first time to be diagnosed as ESCC (ICD-9 150) and who visited any of three medical centers in Taiwan between 2000 and 2009. A standardized questionnaire was used to collect substance uses and other variables.Mean age (±SD) at presentation of ESCC was 59.2 (±11.3) years in a total of 668 cases. After adjusting for other covariates, alcohol drinkers were 3.58 years younger to have ESCC than non-drinkers (p = 0.002). A similar result was found among areca chewers, who were 6.34 years younger to have ESCC than non-chewers (p

This study investigated the tropical cyclone (TC) rainfall (PTC) contribution to the interdecadal change in summer (June, July and August) rainfall (PTotal) over South China between 1981 - 1992 (ID1) and 1993 - 2002 (ID2). In an area-averaged sense, the interdecadal change in PTotal was largely attributed to non-TC rainfall for the summer total and months of June and July, while PTC became comparable in August. When the month-to-month spatial variability was considered, noticeable negative PTC contributions showed up over the southeastern coast, Hainan Island, and Taiwan in June and over the southern coastal regions in July. In contrast, a positive PTC contribution spread over South China with its maxima over the southern coastal regions in August, a pattern which appeared to be diametrically opposed to that of the negative PTC contribution in July, though the latter was less significant. The negative PTC contribution over the coastal and insular regions in June and July corresponded to less TC activity there. In June, it was attributed to reduced basin-wide TC activity due to prevailing unfavorable large-scale environments in ID2, whereas, in July, to less TC approaches from the Philippine Sea due to an enhanced cyclonic circulation centered on Taiwan in ID2. Conversely, in August, the overall enhanced positive PTC contribution was mainly by the direct influences of increased TC formations over the South China Sea in ID2.

On 6 August 2009, typhoon Morakot encountered a giant warm ocean eddy approximately 700 km by 500 km in the southern eddy rich zone of the western North Pacific Ocean. Soon after passing over the warm ocean eddy, Morakot reached its peak intensity at category 2. Results based on multiple satellite observations and numerical modelling suggest very favourable ocean conditions provided by the warm ocean eddy during this earlier developmental stage of Morakot. It is found that in the presence of the observed warm ocean eddy, the upper ocean heat content increased significantly by ~100%, from ~60 to 120 KJ cm -2. This very deep and warm subsurface temperature effectively reduced the negative feedback of typhoon-induced ocean cooling. As a result, the during-storm sea surface temperature remained high at ~29 - 30°C. This very warm during-typhoon sea surface temperature (SST) provided an increase in air-sea enthalpy flux supply by ~200% (i.e., ~500 W m -2 under the warm eddy situation .vs. the ~170 W m -2 under the without eddy situation). Also, since the during-typhoon SST remained high, the moisture supply was increased to enhance convective activities. Numerical experiments using the Weather Research and Forecasting (WRF) model suggest that the presence of the warm ocean eddy does not change the overall structure or characteristics of Morakot. Rather, it contributes to a ~10% increase in Morakot’s precipitation. This research shows that in addition to the favourable atmospheric conditions such as the Intra-Seasonal Oscillation or the southwestern monsoon flow, there also exist favourable ocean conditions provided by the presence of a warm ocean eddy during the early developmental stage of Morakot. Further studies based on a full-physics typhoon-ocean coupled model are needed to quantify the role of the upper ocean features in affecting the evolution of Morakot, including its rainfall over Taiwan.

Typhoon Morakot produced record-breaking accumulated rainfall over southern Taiwan in August 2009. The combination of several factors resulted in this extreme weather event: the steep terrain in Taiwan, the prevailing south-westerly flow in the monsoon trough, Typhoon Goni over the northern South China Sea, and the slow translation speed of Morakot itself over Taiwan. In this study, the influence of the translation speed is particularly emphasized. Based on the EnKF data assimilation, an innovative method is applied to perform ensemble simulations with several designated translation speeds of Morakot using the WRF model. Thus the influence of the translation speed on the amount of accumulated rainfall over Taiwan can be quantitatively evaluated. In the control simulation with observed translation speed, the maximum amount and geographic pattern of accumulated rainfall during the landfall period of Morakot are generally consistent with the observations, though the detailed overall distributions of accumulated rainfall is mostly underestimated, resulting in the low bias of the frequency distribution of the accumulated rainfall. In a simulation with nearly-doubled translation speed of Morakot, the maximum accumulated rainfall is decreased by 33% than that in the control simulation, while the rainfall distribution over Taiwan remains similar. In addition, the 28 ensemble members can further provide additional information in terms of their spread and other statistics. The results from ensemble members reveal the usefulness of ensemble simulations for the quantitative precipitation forecast.