Ileocecal involvement in intestinal Behçet's disease and Crohn's disease: comparison of clinicopathological and immunophenotypic features.

OBJECTIVES: Intestinal Behçet's disease (BD) predominantly affects the ileocecal region and is currently diagnosed based on endoscopic features and clinical manifestations. It is difficult to distinguish between intestinal BD and Crohn's disease (CD) due to similar patient populations, gastrointestinal involvement, extraintestinal manifestations, and long-term recurrent course. In this study we aimed to compare the clinicopathological and immunophenotypic features of intestinal BD to CD. METHODS: The medical and pathological records of 29 cases of intestinal BD and 120 cases of CD diagnosed at Sir Run Run Shaw Hospital were retrospectively analyzed. Immunohistochemistry for CD3, CD20, FOXP3, myeloperoxidase, and quantitative analysis of the infiltrating inflammatory cells was conducted. RESULTS: Intestinal BD with ileocecal ulcer had a higher incidence of abdominal pain and a higher erythrocyte sedimentation rate than CD, while chronic diarrhea was more common in CD. Excessive neutrophils in the mucosal lamina propria, neutrophilic exudate on the ulcer surface, and prominent lymphocytic infiltration in ulcer tissues were statistically more frequent in intestinal BD than in CD. The numbers of FOXP3+ T cells, CD3+ T cells, and CD20+ B cells in biopsy tissue from intestinal BD were significantly higher than CD, but the ratio of FOXP3+ T cells to CD3+ T cells was not statistically different. CONCLUSION: Besides the typical clinical and endoscopic findings, diagnostic biopsies from the ileocecal region in intestinal BD show some histological and immunophenotypic features that are different from CD, which may be useful in distinguishing these two entities.

Quinone oxidoreductase 1 is overexpressed in gastric cancer and associated with outcome of adjuvant chemotherapy and survival.

BACKGROUND: Quinine oxidoreductase 1 (NQO1) plays a vital role in protecting normal cells against oxidative damage and electrophilic attack. It is highly expressed in many solid tumors, suggesting a role in cancer development and progression. However, the role of NQO1 in gastric cancer and its effect on cancer development and prognosis have not been fully investigated. AIM: To investigate the clinical relevance of NQO1 protein expression in gastric cancer and to explore the potential of NQO1 to serve as a prognostic biomarker and therapeutic target. METHODS: In this retrospective study, gastric cancer specimens of 175 patients who were treated between 1995 and 2011 were subjected to immunohistochemistry analyses for NQO1. The correlation of NQO1 expression with gastric cancer prognosis and clinical and pathological parameters was investigated. RESULTS: NQO1 protein was overexpressed in 59.43% (104/175) of the analyzed samples. Overexpression of NQO1 was associated with a significantly inferior prognosis. In addition, multivariate analysis suggested that NQO1 overexpression, along with tumor stage and patient age, are prominent prognostic biomarkers for gastric cancer. Moreover, NQO1 overexpression was correlated to a better response to 5-fluorouracil (5-FU)-based adjuvant chemotherapy. CONCLUSION: NQO1 overexpression is associated with a significantly poor prognosis and better response to 5-FU in patients with gastric cancer. These findings are relevant for improving therapeutic approaches for gastric cancer patients.

Infiltrating regulatory T cells promote invasiveness of liver cancer cells via inducing epithelial-mesenchymal transition.

BACKGROUND: Regulatory T (Treg) cells are a major component of the microenvironment of hepatocellular carcinoma (HCC) contributing to immunosuppression. The present study aimed to evaluate the effects of Treg cells on the invasion potential of HCC. METHODS: Infiltrating Treg cells were isolated from fresh HCC tissues by immunomagnetic bead separation and detected by flow cytometry. Circulating tumor cells (CTCs) were detected using the CellSearch platform. The cell migration and invasion potentials were evaluated by Transwell assays. The cell viability was tested by the cell counting kit-8 (CCK8) approach, and the apoptosis rates were determined by flow cytometry. The concentrations of active transforming growth factor-ß1 (TGFß1) were measured by enzyme-linked immunosorbent assay. RESULTS: Infiltrating Treg cells significantly correlated with the number of CTCs and vascular invasion (both P<0.05). Moreover, these cells could greatly promote HCC migration, invasion, and proliferation, and inhibit HCC apoptosis. Polymerase chain reaction and Western blot assays revealed that Treg cells significantly decreased the expression levels of epithelium-related molecules and increased the expression levels of mesenchyme-related molecules. Treg cells could activate Smad2/3 via secreting TGFß1, and these effects could be impaired by knocking down the expression of TGFß1 in Treg cells. CONCLUSIONS: The involvement of infiltrating Treg cells in triggering the TGFß1 signaling pathway and promoting the epithelial-mesenchymal transition (EMT) of cancer cells during tumor hematogenous dissemination is presumably responsible for increasing the invasiveness potential of HCC cells. Targeting Treg cells in microenvironments can be a promising therapeutic strategy to improve the prognosis for patients with HCC undergoing resection.

Interobserver Agreement in the Diagnosis of Inflammatory Bowel Disease-Associated Neoplasia in China in Comparison to Subspecialized American Gastrointestinal Pathologists.

BACKGROUND: The aim of this study was to evaluate the interobserver variability in diagnosing inflammatory bowel disease (IBD)-associated neoplasia among practicing pathologists from China using telepathology, a practice of remote diagnostic consultation increasingly used nationally and internationally, and its comparison with the interpretation of subspecialized gastrointestinal (GI) pathologists from the United States (US). METHODS: Eight GI pathologists from the US and 4 pathologists from China with an interest in GI pathology participated in this study. A total of 50 colonic biopsies from patients with a clinical history of IBD from 8 medical centers in China were included. All microscopic slides in each case were digitized using an Aperio system. One pathologist (XL) reviewed the digitized full-slide images, and selected areas of interest were captured at low, medium, and high magnifications at a resolution of 1712 × 1072 pixels and saved as tagged image file format (TIFF) files on read-only DVD. Each pathologist evaluated the images and selected the most appropriate diagnostic category for each case (negative, indefinite, low-grade dysplasia [LGD], high-grade dysplasia [HGD], and carcinoma). A Fleiss' kappa coefficient (K) analysis was performed to determine interobserver agreement and the agreement of each pathologist from China with the consensus diagnosis (defined as diagnostic agreement by at least 4 participating US GI pathologists). RESULTS: There was substantial interobserver agreement among 4 pathologists from China on the interpretation of IBD-associated neoplasia (kappa value 0.68, 95% confidence interval: 0.56-0.78). A consensus diagnosis included negative (n = 22), LGD (n = 22), HGD (n = 3), carcinoma (n = 2), and indefinite for dysplasia (n = 1). Using consensus diagnoses as references, the agreement between each pathologist from China and the consensus diagnosis was substantial with kappa values ranging from 0.75 to 0.80. CONCLUSIONS: This study reveals substantial interobserver agreement for the interpretation of colonic neoplasia in IBD using digitized images among Chinese pathologists as well as between each Chinese pathologist and a consensus diagnosis generated by US GI pathologists.

Malignant glomus tumor of the lung with multiorgan metastases: case report and literature review.

Glomus tumor is an exceedingly rare neoplasm that is derived from cells of the neuromyoarterial glomus or glomus body. It rarely occurs in the visceral organs where glomus body may be sparse or even absent, such as the stomach, intestines, mediastinum, and respiratory tract. It is unusual for a glomus tumor to demonstrate atypical or malignant histopathological characteristics. It is also rare for such a tumor to express clinically aggressive behavior. However, when metastasis does occur, this disease is often fatal. We herein report an interesting case of a middle-age woman admitted due to progressive cough and hemoptysis. A polypoid mass was found to occlude the left lingular lobar bronchus. Final histopathologic examination showed the presence of malignant glomus tumor, confirmed by immunoreactivity for smooth muscle actin and vimentin. Two months later, the patient developed abdominal distension and gastrointestinal bleeding. Further evaluation lead to the discovery of widespread metastatic disease to the gastrointestinal tract, spleen, and the left adrenal gland. We further entail a review of the literature on the clinicopathologic features and diagnosis of this uncommon tumor.

Primary hepatic angiosarcoma: A report of two cases and literature review.

Primary hepatic angiosarcoma (PHA) is a rare malignancy that carries a poor prognosis. Of 1500 patients who underwent hepatectomy for primary hepatic tumors between 1994 and 2013 at our center, two patients were pathologically diagnosed with PHA. Clinical characteristics, treatment modalities, and outcomes of the two patients were collected and analyzed. Both patients underwent hepatectomy and had a postoperative survival time of 8 and 16 mo, respectively. A search of PubMed yielded eight references reporting 35 cases of PHA published between 2004 and 2013. On the basis of the presented cases and review of the literature, we endorse complete surgical resection as the mainstay definitive treatment of PHA, with adjuvant postoperative chemotherapy potentially improving survival. Palliative chemotherapy is an option in advanced hepatic angiosarcoma.

FOXA1 Expression Significantly Predict Response to Chemotherapy in Estrogen Receptor-Positive Breast Cancer Patients.

PURPOSE: Most estrogen receptor (ER)-positive breast cancer responds poorly to chemotherapy and no single cost-effective biomarker capable of selecting chemosensitive ones has been found yet. We investigated FOXA1 for its role in predicting chemosensitivity of this subgroup in neoadjuvant chemotherapy settings. METHODS: We reviewed pathologic slides of 123 patients who were diagnosed with ER-positive breast cancer on core needle biopsy and underwent neoadjuvant chemotherapy at our institution between 2002 and 2012. FOXA1 expression and pathologic response were evaluated. We then statistically analyzed FOXA1 expression and its relationship with chemosensitivity. RESULTS: FOXA1 expression before NAC was correlated with poor chemoresponse in ER-positive as well as luminal A and luminal B breast cancer patients (p = 0.002, 0.001, and 0.049 respectively). Significant association between change of FOXA1 staining position after NAC and chemosensitivity also was observed (p = 0.024). Multivariate analysis identified FOXA1 expression before NAC as an independent predictor of chemosensitivity in ER-positive and luminal A breast cancer patients [p = 0.002; relative risk (RR) 0.163; 95 % confidence interval (CI) 0.053-0.500, and p = 0.002; RR 0.055; 95 % CI 0.008-0.353, respectively]. Additionally, change of FOXA1 staining position after NAC was shown to be an independent predictor of chemoresponse in luminal B subtype breast cancer patients (p = 0.012; RR 0.153; 95 % CI 0.035-0.665). CONCLUSIONS: FOXA1 expression can independently predict chemosensitivity of ER-positive breast cancer patients.

The transcription factor KLF4 as an independent predictive marker for pathologic complete remission in breast cancer neoadjuvant chemotherapy: a case-control study.

BACKGROUND: To identify whether a stem cell biomarker, KLF4, may predict the pathologic tumor response to neoadjuvant chemotherapy for patients with locally advanced breast cancer. METHODS: Twelve locally advanced breast cancer patients who achieved pathologic complete remission (pCR) after neoadjuvant chemotherapy were identified and for each, three non-pCR breast cancer patients - matched for age, clinical tumor-node-metastasis stage, and neoadjuvant chemotherapy cycles - were selected. The relationship between KLF4 expression in the core needle biopsied cancer tissue and patient pCR rate was assessed using univariate and multivariate analysis. RESULTS: Receiver operating characteristic curve analysis showed that the patients with a histoscore of KLF4 expression >0.18 had a lower pCR rate. Multivariable analysis showed that higher KLF4 expression (odds ratio 0.013; 95% confidence interval 0.013-0.444; P=0.004) was independently correlated with a lower pCR rate after neoadjuvant chemotherapy. CONCLUSION: KLF4 overexpression was associated with lower pCR in locally advanced breast cancer patients undergoing neoadjuvant chemotherapy. This study suggests that KLF4 may serve as a predictor for pCR in patients with breast cancer after neoadjuvant chemotherapy.

Estrogen receptor α roles in breast cancer chemoresistance.

Resistance to chemotherapy treatment, which may lead to limited efficacy of systemic therapy in breast cancer patients, is multifactorial. Among the mechanisms of resistance to chemotherapy treatment, there are those closely related to estrogen receptor α, P-glycoprotein, multidrug resistance-related protein, glutathione S-transferase pi and topoisomerase-II. ERα is ligand-activated transcription factor that regulates gene expression and plays a critical role in endocrine signaling. In previous preclinical and clinical studies, positive ERα expression in breast cancer cells was correlated with decreased sensitivity to chemotherapy. This article reviews current knowledge on the predictive value of ERα with regard to response to chemotherapy. Better understanding of its role may facilitate patient selection of therapeutic regimens and lead to optimal clinical outcomes.

Isolated splenic metastases from gastric carcinoma: a case report and literature review.

Isolated metastases to the spleen from gastric carcinoma is very rare. Only a few cases have been reported in the literature. We herein present a case of isolated splenic metastases in a 62-year-old man, occurring 12 mo after total gastrectomy for gastric carcinoma. The patient underwent a laparoscopic exploration, during which two lesions were found at the upper pole of the spleen, without involvement of other organs. A laparoscopic splenectomy was performed. Histological examination confirmed that the splenic tumor was a poorly differentiated adenocarcinoma similar to the primary gastric lesion. The postoperative course was uneventful and the patient has been well for 9 mo, with no tumor recurrence. The clinical data of 18 cases of isolated splenic metastases from gastric carcinoma treated by splenectomy were summarized after a literature review. To our knowledge, this is the first reported case of isolated splenic metastases undergoing laparoscopic splenectomy.

Small intestinal hemolymphangioma with bleeding: a case report.

Small intestinal hemolymphangioma is a very rare benign tumor. There was only one report of a hemolymphangioma of the pancreas invading to the duodenum until March 2011. Here we describe the first case of small intestinal hemolymphangioma with bleeding in a 57-year-old woman. She presented with persistent gastrointestinal bleeding and endoscopy revealed a small intestinal tumor. Partial resection of the small intestine was thus performed and the final pathological diagnosis was hemolymphangioma. We also highlight the difficultly in making an accurate preoperative diagnosis in spite of modern imaging techniques. To arrive at a definitive diagnosis and exclude malignancy, partial resection of the small intestine was considered to be the required treatment.

Pulmonary vein sarcoma: a case report.

Recently, we treated a patient with pulmonary vein sarcoma. The patient was a 41-year-old woman, had cough, short of breath and apsychia, with obvious jugular venous distention, rales in both lungs and a diastolic murmur at the apex. CT and Echo revealed a tumor in the left atrium. She received an emergency surgery to remove the mass in the heart. The pathological diagnosis demonstrated it as leiomyosarcoma. Though the patient accepted radiotherapy and chemotherapy, she still died of recurrence and metastasis of the sarcoma 10 months after operation.

Changes of histology and expression of MMP-2 and nm23-H1 in primary and metastatic gastric cancer.

AIM: To investigate the changes of histology and expression of MMP-2 and nm23-H1 in primary and metastatic gastric cancer. METHODS: One hundred and seventy-seven gastric cancer patients with lymph node and/or distal metastasis between 1997 and 2001 were reviewed. Differences in histology of the primary and metastatic gastric cancer were assessed. MMP-2 and nm23-H1 immunoreactivity was compared in 44 patients with tumor infiltration to the serosa layer. RESULTS: Poorly and moderately differentiated metastatic gastric cancer was found in 88.7% (157/177) and primary gastric cancer in 75.7% (134/177) of the patients. The histological type of metastatic gastric cancer that was not completely in accordance with the preponderant histology of primary gastric cancer was observed in 25 patients (14.1%). MMP-2 immunoreactivity in metastatic gastric cancer was significantly stronger than that in primary gastric cancer, while nm23-H1 immunoreactivity showed no difference in primary and metastatic gastric cancer. CONCLUSION: Metastatic gastric cancer presents more aggressive histological morphology and higher MMP-2 immunoreactivity than primary gastric cancer. This heterogeneity may elicit a possible mechanism of gastric cancer metastasis.