Diagnostic Utility of Cytomegalovirus (CMV) DNA Quantitation in Ulcerative Colitis.

Cytomegalovirus (CMV) colitis is a critical condition associated with severe complications in ulcerative colitis (UC). This study aimed to investigate the diagnostic value of the presence of CMV DNA in intestinal mucosa tissue and blood samples in patients with active UC. This study included 81 patients with exacerbated symptoms of UC. Patient data were obtained from the Hospital Information Management System. CMV DNA in colorectal tissue and plasma samples were analyzed using a real-time quantitative PCR assay. CMV markers were detected using immunohistochemistry and hematoxylin-eosin staining. Immunohistochemistry positivity was observed in tissue samples from eight (9.9%) patients. Only one (1.2%) patient showed CMV-specific intranuclear inclusion bodies. CMV DNA was detected in 63.0% of the tissues (median: 113 copies/mg) and in 58.5% of the plasma samples (median: 102 copies/mL). For tissues, sensitivity and the negative predictive value (NPV) for qPCR were excellent (100.0%), whereas specificity and the positive predictive value (PPV) were low (41.9% and 15.7%, respectively). For plasma, sensitivity and NPV were high (100.0%) for qPCR, whereas specificity and PPV were low (48.6% and 24.0%, respectively). CMV DNA ≥392 copies/mg in tissue samples (sensitivity 100.0% and specificity 83.6%) and ≥578 copies/mL (895 IU/mL) in plasma samples (sensitivity 66.7% and specificity 100.0%) provided an optimal diagnosis for this test. The qPCR method improved patient management through the early detection of CMV colitis in patients with UC. However, reliance on qPCR positivity alone can lead to overdiagnosis. Quantification of CMV DNA can improve diagnostic specificity, although standardization is warranted.

Leaf Extract from European Olive (Olea europaea L.) Post-Transcriptionally Suppresses the Epithelial-Mesenchymal Transition and Sensitizes Gastric Cancer Cells to Chemotherapy.

The overall survival of patients with the advanced and recurrent gastric cancer (GC) remains unfavorable. In particular, this is due to cancer spreading and resistance to chemotherapy associated with the epithelial-mesenchymal transition (EMT) of tumor cells. EMT can be identified by the transcriptome profiling of GC for EMT markers. Indeed, analysis of the TCGA and GTEx databases (n = 408) and a cohort of GC patients (n = 43) revealed that expression of the CDH2 gene was significantly decreased in the tumors vs. non-tumor tissues and correlated with the overall survival of GC patients. Expression of the EMT-promoting transcription factors SNAIL and ZEB1 was significantly increased in GC. These data suggest that targeting the EMT might be an attractive therapeutic approach for patients with GC. Previously, we demonstrated a potent anti-cancer activity of the olive leaf extract (OLE). However, its effect on the EMT regulation in GC remained unknown. Here, we showed that OLE efficiently potentiated the inhibitory effect of the chemotherapeutic agents 5-fluorouracil (5-FU) and cisplatin (Cis) on the EMT and their pro-apoptotic activity, as was demonstrated by changes in the expression of the EMT markers (E- and N-cadherins, vimentin, claudin-1) in GC cells treated with the aforementioned chemotherapeutic agents in the presence of OLE. Thus, culturing GC cells with 5-FU + OLE or Cis + OLE attenuated the invasive properties of cancer cells. Importantly, upregulation of expression of the apoptotic markers (PARP cleaved form) and increase in the number of cells undergoing apoptosis (annexin V-positive) were observed for GC cells treated with a combination of OLE and 5-FU or Cis. Collectively, our data illustrate that OLE efficiently interferes with the EMT in GC cells and potentiates the pro-apoptotic activity of certain chemotherapeutic agents used for GC therapy.

Microscopic Growth Pattern of Metastatic Colorectal Carcinomas, Morphological Findings of the Non-Neoplastic Liver, and Their Relationship With Prognosis and Survival.

Introduction. Various clinicopathological, radiological, and molecular parameters are predictive of prognosis in patients with colorectal carcinoma and distant organ metastases continue to have a significant place among them. Recent studies reveal that not only the presence of metastases but also the histopathological growth pattern of the metastatic tumor significantly affects prognosis. This study aimed to investigate the prognostic significance of the histopathological growth patterns of metastatic tumors, the morphological findings in the peritumoral non-neoplastic liver, and its relationship with survival in patients who have metastatic colorectal carcinoma. Materials and Method. Hematoxylin and eosin-stained slides of the tumors were re-examined in terms of histopathological diagnosis, growth pattern, presence and degree of peritumoral lymphocytic infiltration, steatosis, cholestasis, and peritumoral ductular reaction in the non-neoplastic liver. Results. In terms of histopathological growth patterns, 24 (47%) tumors showed replacement, 19 (37%) showed desmoplastic and 8 (16%) showed pushing growth pattern. In terms of total survival, there was a significant difference (P = .011) between desmoplastic and replacement growth patterns, and the survival period was shorter in patients with replacement growth patterns. Conclusion. Recent studies show that histopathological growth patterns in metastatic liver tumors may be a promising prognostic and predictive parameter. It is important to include this parameter in the pathology reports as it does not require additional equipment for evaluation in routine pathology practice, does not bring additional costs, or takes a long time to evaluate. This feature can be evaluated standardly by every pathologist.

Liver metastasis of breast carcinoma: An unusual presentation and growth pattern.

Breast carcinoma is one of the tumors that frequently metastasize to the liver. Extramedullary hematopoiesis (EMH) usually occurs due to insufficient medullary hematopoiesis. In this case report, we present a female patient with sinusoidal breast carcinoma metastasis and extramedullary hematopoiesis in liver biopsy. A 63-year-old female patient with history of breast carcinoma was admitted to our center with respiratory distress. Pleural effusion was detected and thoracentesis was planned. Treatment was given after detection of non-mycobacterial tuberculosis bacillus in the thoracentesis fluid. Antibiotherapy was terminated due to elevation of liver enzymes and bilirubin. The patient's clinical status was evaluated and treatment was re-initiated. The patient did not have any mass lesion in the liver. Tru-cut biopsy was performed to evaluate a possible tuberculosis involvement in the liver. The diagnosis of metastatic breast carcinoma located in the sinusoidal area and cholestatic liver with extramedullary hematopoiesis foci was given using the histomorphological, immunohistochemical and histochemical findings. Radiological evaluation has an important role in staging of malignancies. However, it should be kept in mind that hepatic metastases may present without formation of a mass lesion, and unexpected laboratory results of cases without abnormal radiological features should raise the suspicion of a metastasis. Such materials should be evaluated in detail by making multiple serial sections in the pathology laboratory. Rare metastatic tumor growth patterns not causing a mass lesion such as sinusoidal or portal pattern, should also be kept in mind.

Early-stage colon cancer with high MALAT1 expression is associated with the 5-Fluorouracil resistance and future metastasis.

BACKGROUND: This study aimed to investigate the role of long noncoding RNA (LncRNA) expression profiles to predict relapse and 5-FU response in patients with stage I/II colon cancer (CC). METHODS AND RESULTS: The expression level of 15 LncRNA was analyzed in stage I/II colon tumors of 126 CC patients. To confirm the findings in-vitro, 5FU-resistant HT29 cells were generated by subjecting HT-29 cells to the increasing concentrations of 5FU for 6 months. The 5FU resistance was observed in WST-1 and Annexin V analyses. The colony formation and wound healing assays were assessed to determine the metastatic properties of the cells. Expression levels of LncRNAs and mRNA of EMT-related genes were determined by RT-PCR. The role of LncRNA on metastasis and 5FU sensitivity were confirmed in pcDNA3.0-PTENP1 and si-MALAT1 expressed 5FU-resistant HT29 cell lineages. RESULTS: High MALAT1 (p = 0.0002) and low PTENP1 (p = 0.0044) expressions were significantly associated with 5-FU resistance and tumor relapse in stage I/II CC. The invasiveness and colony-forming characteristics of 5-FU-resistant cell lineages were higher as compared to the parent HT-29. Moreover, the expression of MALAT1 (p = 0.0009) was increased while the expression of PTENP1 (p = 0.0158) decreased in 5FU-resistant-HT-29 cells. Si-MALAT1 treatment increased cell sensitivity to 5FU, whereas it decreased invasive behaviors of 5 FU-resistant-HT-29 cells. CONCLUSION: MALAT1 may be a biomarker in predicting recurrence in early-stage CC. Our findings suggest that a cell-based therapy to target MALAT1 could be established for these patients to prevent metastasis and 5-FU resistance.

Do morphologic characteristics play a role in nodal metastatic progression of well-differentiated pancreatic neuroendocrine tumors?

BACKGROUND: Pancreatic neuroendocrine neoplasms (NENs) are tumors with histopathologic and prognostic heterogeneity that pose difficulties in establishing standards for diagnosis, classification, and treatment. Among NENs, well-differentiated neuroendocrine tumors (NETs) have been classified as grade 1, 2, and 3 in the most recently released World Health Organization classification. Although well-differentiated NETs are associated with relatively better prognosis, they have a potential for malignant behavior such as extrapancreatic spread, metastasis, or recurrence. The present study aimed to evaluate clinical and histomorphologic findings of patients with well-differentiated pancreatic NETs and to identify histopathologic findings effective in predicting nodal metastatic progression. METHODS: The study group consisted of 54 patients diagnosed with well-differentiated NET. All preparations and blocks of the patients were examined for the following histopathologic parameters: tumor diameter, microscopic tumor growth pattern (solid, trabecular, acinar, and mixed), cellular features (clear, eosinophilic, oncocytic, peliotic, and pseudopapillary), stromal changes (calcification, lymphocytic infiltration, and stromal hyalinization), presence of necrosis, perineural invasion, lymphovascular invasion, mitotic activity, and Ki67 proliferative index. RESULTS: Lymph node metastasis was present in 7 patients. Lymph node metastasis was significantly associated with tumor diameter of >2 cm (p = 0.012), Ki67 proliferative index of >20% (p = 0.022), grade 3 tumors (p = 0.002), presence of dense stromal hyalinization (p = 0.034), and mild lymphocytic infiltration (p = 0.041). CONCLUSION: The present study revealed that the new findings such as presence of dense stromal hyalinization and absence of remarkable lymphocytic infiltration could be predictive morphologic findings for the development of lymph node metastasis.

Insulinoma Case Admitted with Reactive Hypoglycemia Symptoms.

AIM: To present an insulinoma case with post-prandial hypoglycemic symptoms associated with glucose inducible endogenous hyperinsulinemia. CASE: A 52-year-old female patient was evaluated for hypoglycemic symptoms especially those occuring within 3 hours after consuming sugary foods. These symptoms were persistent for a year and a half. She was diagnosed with reactive (post-prandial) syndrome and followed a recommended diet and was given acarbose but there was no improvement. The results suggested post-prandial endogenous hyperinsulinemia related hypoglycemia. Multiphasic computerized tomography revealed an 11x15x12 mm size mass lesion, anteriorly in the head and uncinate process of the pancreas and then the patients were treated surgically with pancreatic enucleation and cured. CONCLUSION: Distinguishing post-prandial syndrome by careful history and clinical evaluation in patients with postprandial symptoms is of great importance in terms of cost-effectivity. However, it should not be forgotten that although organic pathologies are mostly presented with fasting hypoglycemia, they may also cause post-prandial symptoms. Severity and progression of the symptoms that point to neuroglycopenia is important, and in this condition the most convenient clinical approach to the patient should be performed with careful and appropriate assessment steps.

Effect of chitosan coating on surgical sutures to strengthen the colonic anastomosis.

BACKGROUND: We evaluated the feasibility of chitosan-coated sutures for intestinal anastomosis strength through wound-healing effect. METHODS: Vicryl and PDS sutures were coated with 2% chitosan. While laparotomy was applied to the first group, chitosan was applied in the peritoneal cavity in the second group. Then the following materials were applied to colon anastomosis, in order: Vicryl, PDS, chitosan-coated Vicryl, and chitosan-coated PDS sutures. On the 7th and 14th days, eight rats from each group were euthanized. RESULTS: The adhesion scores of chitosan and control groups were lower than the suture groups. The vascularization of Vicryl-chitosan was lower than PDS-chitosan on the 14th day (p=0.038). Fibroblast cells and vascularization of anastomosis with chitosan-coated Vicryl were lower than Vicryl and chitosan-coated PDS on the 14th day (p<0.05). The tensile strength of Vicryl-chitosan increased more than Vicryl in vitro (p<0.05) on the 14th and 7th days, but there was no difference in vivo. The tensile strength of PDS-chitosan decreased more than PDS on the 7th day in vivo (p<0.05). CONCLUSION: The chitosan-coating effect on the adhesion and reinforcement of anastomosis in some parts of Vicryl in vitro and PDS in vivo was slightly improved.

Perforation of the small intestine caused by enteropathy-associated T cell lymphoma.

Enteropathy-associated T cell lymphoma is a rare lymphoma specific to the gastrointestinal system, arising from intraepithelial T lymphocytes, that is often associated with celiac disease. We report a 53-year-old female patient with no previous disease who presented with severe abdominal pain. Physical examination revealed diffuse abdominal tenderness and abdominal guarding and the patient underwent emergency surgery with a diagnosis of acute abdomen. During the operation, a 20-cm mass was found located on Treitz ligament, invading the duodenum and pancreatic head and perforating the jejunum. Histologically, medium-sized monomorphic atypical lymphocyte infiltration with dark nucleus and narrow cytoplasm was seen in the layers of mucosa, submucosa, muscular wall, and serosa of the duodenum. The final pathological diagnosis was "enteropathy-associated T cell lymphoma type 2" based on immunohistochemical and serological findings. Based on the World Health Organization 2008 criteria, enteropathy-associated T cell lymphoma has two subtypes. Type 1 enteropathy-associated T cell lymphoma is associated with celiac disease and has HLA DQ2 and HLA DQ8 genotype. Enteropathy-associated T cell lymphoma 2 enteropathy-associated T cell lymphoma seldom occurs and is not associated with celiac disease.

Coexistence of gastric multiple neuroendocrine tumors with unusual morphological features and gastric signet-ring cell carcinoma.

The coexistence of signet-ring cell carcinoma and neuroendocrine tumors is very rare. We report a 57-year-old man who presented with a history of weight loss and nausea. Gastric mucosal biopsies obtained during gastrointestinal endoscopy revealed a gastric signet-ring cell carcinoma. The patient underwent a total gastrectomy with a standard D2 lymph node dissection. Ten individual tumors were detected in the resected specimen. Based on the histopathological and immunohistochemical findings, the final diagnosis was co-existing signet-ring cell carcinoma and neuroendocrine tumor. Spindle-shaped cells and extracytoplasmic mucin were noted in some tumor cells forming the neuroendocrine component. This case is a rare synchronous tumor because of its unusual neuroendocrine component.

Coexistence of MACC1 and NM23-H1 dysregulation and tumor budding promise early prognostic evidence for recurrence risk of early-stage colon cancer.

The tumor-node-metastasis (TNM) classification, the presence of a mucinous component, and signet ring cells are well-known criteria for identifying patients at a high risk for recurrence and determining the therapeutic approach for early-stage colon cancer (eCC). Nevertheless, recurrence can unexpectedly occur in some eCC cases after surgical resection. The aims of the present study were to evaluate the relation of dysregulated MACC1, c-MET, and NM23-H1 expression with the histopathological features of tumors in recurrence formation in eCC cases. A total of 100 sporadic eCC patients without poor prognosis factors were evaluated in this study. The relationship between the altered expression of MACC1, c-MET, and NM23-H1 and pathological microenvironmental features, including the presence of tumor budding and desmoplasia, were assessed. The primary outcomes, including 5-year overall survival (OS) and disease-free survival (DFS), were also measured. Compared with nonrecurrent patients, the expression level of MACC1 was 8.27-fold higher, and NM23-H1 was 11.36-fold lower in patients with recurrence during the 5-year follow-up (p = 0.0345 and p = 0.0301, respectively). In addition, the coexistence of high MACC1 and low NM23-H1 expression and tumor budding was associated with short OS (p < 0.001). We suggest that the combination of reduced NM23-H1, induced MACC1, and the presence of tumor budding are promising biomarkers for the prediction of recurrence and may aid the stratification of patients with stage II colon cancer for adjuvant chemotherapy.

Overexpression of the Long Noncoding RNA HomeoboxA Transcript at the Distal Tip Predicts Poor Prognosis in a KRAS-Independent Manner in Periampullary Region Tumors.

OBJECTIVES: Periampullary region tumors (PRTs) are the fifth highest cause of cancer-related deaths worldwide. Although recent studies have highlighted the prognostic value of the long noncoding RNA HomeoboxA transcript at the distal tip (HOTTIP) in patients with pancreatic ductal adenocarcinoma, the relationship between HOTTIP and clinical outcome of all PRTs remains obscure. The aim of this study was to clarify the prognostic significance of HOTTIP in patients with all PRTs related to KRAS mutational status. METHODS: HomeoboxA transcript at the distal tip expression was detected in 100 PRT samples using quantitative real-time polymerase chain reaction. The associations between HOTTIP levels, clinicopathological factors, and patient prognosis were also analyzed. RESULTS: The expression of HOTTIP was found to be significantly upregulated by 32-fold (P = 0.031) in tumor tissues compared with normal tissues. The over expression of HOTTIP was related with presence of invasion and metastasis (P = 0.0467, P = 0.0256). In addition, increased HOTTIP expression was associated with poor prognosis independent of KRAS mutation (P < 0.001; n = 72). Moreover, multivariate analysis showed that high HOTTIP expression was an unfavorable prognostic factor for overall survival. CONCLUSIONS: Our findings indicate that high levels of HOTTIP expression have the potential to be an independent, unfavorable prognostic factor for patients with PRT.

Enhancer of zeste homologue 2 (EZH2) expression in synovial sarcomas as a promising indicator of prognosis.

Synovial sarcoma (SS) is a type of soft-tissue sarcoma, often linked to poor survival. Although overexpression of enhancer of zeste homologue 2 (EZH2) has been associated with poor prognosis in different tumors, a few studies investigated this link in SS. Here, we analyzed the relationship between EZH2 expression and prognostic factors in SS. We included 29 patients with SS. Immunostaining of EZH2 was performed with (D2C9) XPTM Rabbit mAb antibody, and the results were classified as low EZH2 expression (negative or weak expression) and high EZH2 expression category (moderate or strong expression). Analysis of survival in relation to prognostic factors was performed with Kaplan-Meier survival curves and Cox proportional hazard regression analysis. Our sample included 19/29 female and 10/29 male patients, with age range 16-63 years. The tumor diameter ranged from 2 to 15 cm. Necrosis was observed in 15/29 cases. Sixteen cases had >10 mitoses per 50 high-power fields (HPFs). Out of 29 cases, 14 showed low and 15 had high EZH2 expression. Statistically significant results were obtained for the association between the presence of metastasis and necrosis (p = 0.042), high EZH2 expression and distant metastasis (p = 0.018), high EZH2 expression and necrosis (p = 0.016), and high EZH2 expression and the tumor size >5 cm versus tumor size ≤5 cm (p = 0.014). Patients with all of the following: the tumor size ≤5 cm, low EZH2 expression, and without necrosis and distant metastasis had significantly longer survival time. Our results are consistent with previous studies, suggesting that EZH2 overexpression is an indicator of poor prognosis in SS.

A Mimicker of Gallbladder Carcinoma: Cystic Gastric Heterotopia with Intestinal Metaplasia.

Heterotopic gastric mucosa in the gallbladder is an unusual entity and is usually clinically silent. We report a 75-year-old female patient who presented with intermittent upper abdomial pain radiating to the back. Abdominal imaging studies showed a sessile polypoid lesion and a gallstone in the gallbladder. Gallbladder carcinoma was suspected and cholecystectomy performed. Intraoperative frozen section examination suggested mucinous tumor, suspicious for malignancy. However, the permanent sections revealed aberrant gastric tissue consisted of gastric pyloric and fundic glands of heterotopic gastric mucosa with intestinal metaplasia in the gallbladder.

Immunohistochemical expression of CDX2, CK7, HER2 and HER4 in periampullary adenocarcinoma : implications for clinicopathology and patient outcomes.

Background: Periampullary carcinomas originate from the pancreatic head, the ampulla, the distal bile duct, or the duodenum. The expression of CK7 and CDX2 has been used in the classification of periampullary carcinomas. There is prognostic value of human epidermal growth factor receptor (HER) 2 and HER 4, which have been linked to poor prognosis in several types of tumors, such as breast and gastric carcinomas. We aimed to evaluate the expression and prognostic value of CDX2, CK7, HER 2, and HER4 in periampullary adenocarcinoma. Patients and Methods: We retrospectively selected 98 patients who had undergone pancreatoduodenectomy for periampullary adenocarcinoma at our pathology department. The tumor location, pathological subtype, involvement of vessels and lymph nodes, perineural invasion, clinical follow-up, and tumorstage were noted. Immunohistochemistry was performed for CK7, CDX2, HER2, and HER4. Results: CDX2 staining was predictive of perineural invasion. Additionally, there was a significant association between the overexpression of HER2 and HER4 and the presence of perineural invasion. HER4 was significantly positive in patients with the pancreatobiliary subtype compared with patients with the intestinal subtype. Patients with the pancreatobiliary subtype, lymph node involvement, and advanced pT and UICC stages had significantly lower median survival. Conclusion: Our findings suggest that only pancreatobiliary subtype, lymph node involvement and advanced pT and UICC stages were independent predictors of short survival, but the ampulla tumor location predicted a significantly better survival time. The immunohistochemical expression of CDX2, CK7, HER4, and HER2, vessel involvement, and perineural invasion were not associated with the survival of patients with periampullary adenocarcinoma.

Immunohistochemical expression of human epidermal growth factor receptor (HER)-4 and prognosis in patients with metastatic breast cancer.

PURPOSE: The clinical value of HER4 - a cell surface receptor that belongs to the human epidermal growth factor receptor family - for predicting survival outcomes in patients with breast cancer remains controversial. Herein, we sought to investigate the prognostic significance of HER4 immunohistochemical expression with respect to progression-free survival (PFS) and overall survival (OS) in Turkish patients with metastatic breast cancer (MBC). METHODS: MBC patients (N=45; mean age=50.5±12.7 years) were consecutively enrolled between 2000 and 2006 in the Department of Oncology at the Uludag University Medical Center, Bursa, Turkey. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded sections. The predictive value of HER4 expression was investigated by multivariate analysis after allowance for potential confounders. RESULTS: The mean PFS in the study participants was 11.35 months (range:1-50), whereas the median OS was 22.18 months (range:1-76). The mean PFS in patients with a HER4 immunohistochemical score of 0, 1+, 2+, and 3+ was 11.0 ± 4.8, 11.3 ± 7.7, 11.7 ± 8.1, and 10.4 ± 7.4 months, respectively (p=0.99) . The mean OS in patients with a HER4 score of 0, 1+, 2+, and 3+ was 13.3 ± 6.8, 25.6 ± 10.8, 22.9 ± 10.7, and 13.5 ± 9.9, months, respectively (p=0.44). The results of multivariate Cox regression analysis indicated that the presence of visceral metastases was the only independent prognostic factor for both OS (HR=3.01, 95% CI=1.56-3.99, p <0.01) and PFS (HR=2.91, 95% CI=1.51-3.78, p <0.01). CONCLUSION: HER4 immunohistochemical expression is not an independent predictor of OS and PFS in Turkish MBC patients.

Retrospective analysis of clinicopathological features of solid pseudopapillary neoplasm of the pancreas.

Solid pseudopapillary neoplasm (SPN) of the pancreas is a rare neoplasm that accounts for 2-3% of all primary pancreatic neoplasms. This study aimed to characterize clinicopathological features associated with SPNs and to retrospectively evaluate the relationship of these features with predictive parameters associated with aggressive behavior. We reviewed 16 cases of SPN of the pancreas that had been diagnosed between 2005 and 2014 at our pathology department. A total of 16 cases, 15 female and one male, were evaluated in this study. The patient age ranged from 13 years to 63 years with a median of 35.70 years. The mean tumor diameter ranged from 2 cm to 18 cm with a mean diameter of 5.90 cm. We identified a significant association between the presence of clear cells and perineural invasion (p=0.019), which was considered to be a predictive factor for aggressive behavior. Other features (i.e., localization, nuclear grooves, central hyalinization, myxoid stroma, eosinophilic bodies, foamy histiocyte aggregates, multinucleated cells, and calcification) were not significantly associated with predictive factors for aggressive behavior. One patient died as a result of a pancreatic fistula that developed as a postoperative complication. The remaining 15 patients are alive and have not demonstrated any signs of recurrence or metastasis. The current study suggested that the presence of clear cells might serve as a possible prognostic indicator of perineural invasion, which is a predictive parameter associated with aggressive behavior in SPN.

Impact of 3'UTR variation patterns of the KRAS gene on the aggressiveness of pancreatobiliary tumors with the KRAS G13D mutation in a Turkish population.

OBJECTIVE: Several studies have demonstrated the importance of mutations in codons 12, 13 and 61 and variations in the 3' untranslated region (3'UTR) of the KRAS gene, frequently observed genetic events in the progression of pancreatobiliary tumors (PBT). However, limited data exist on the clinical effect of these alterations. The aim of the current study was to clarify the frequency of relevant alterations of the 3'UTR regions of the KRAS gene and the effect of KRAS 3'UTR polymorphisms on the prognosis of patients with codon 12, 13 and 61 mutations in a Turkish population with PBT. METHODS: Codons 12, 13, and 61 and 3'UTRs of the KRAS gene were screened by single-strand conformation polymorphism (SSCP) analysis and DNA sequencing in 43 patients and 10 controls. Chi-squared and independent sample T tests were used to evaluate the results of the mutation analysis and clinical features of the patients. RESULTS: We defined the c.38G > A (rs112445441, p.G13D) (39.54%) mutation and two 3'UTR variations, c.*4066delA (rs560890523) (23.26%) and c.*4065_*4066delAA (rs57698689) (6.98%), in the KRAS gene of Turkish patients. There was a statistically significant relationship between the c.*4066delA (rs560890523) and c.*4065_*4066delAA (rs57698689) variations and invasion and lymph node metastasis status of the patients (p < 0.001). Compared to patients with c.38G > A (rs112445441, p.G13D), patients with c.*4066delA (rs560890523) and c.38G > A (rs112445441, p.G13D) presented more aggressive tumors with highly invasive features. The present study contributes findings regarding the clinical effects of KRAS alterations in PBT. Based on our study, further investigations are required.

Effects of Systemic and Local Interferon Beta-1a on Epidural Fibrosis.

STUDY DESIGN: Level 1 randomized controlled study. PURPOSE: To investigate the effects of systemic and local interferon-beta-1a (IFN-ß-1a) on prevention of epidural fibrosis using histopathological parameters. OVERVIEW OF LITERATURE: Epidural fibrosis involves fibroblastic invasion of nerve roots into the epidural space. Formation of dense fibrous tissue causes lumbar and radicular pain. Many surgical techniques and several materials have been proposed in the literature, but no study has assessed the effect of IFN-ß-1a on prevention of epidural fibrosis. METHODS: Forty-eight adult female Sprague-Dawley rats were divided into six groups of eight: sham group, control group, systemic 44 µg IFN-ß-1a group and 22 µg IFN-ß-1a group (after laminectomy and discectomy, 0.28 mL and 0.14 mL IFN-ß-1a applied subcutaneously three times for a week, respectively), local 44 µg IFN-ß-1a group (laminectomy and discectomy, followed by 0.28 mL IFN-ß-1a on the surgical area), and local 22 µg IFN-ß-1a group (laminectomy and discectomy, followed by 0.14 mL IFN-ß-1a on the surgical area). All rats were sacrificed after 4 weeks and groups were evaluated histopathologically. RESULTS: Compared with sham and control groups, significantly less epidural fibrosis, dural adhesion, and fibroblast cell density were observed in the local and systemic 44 µg IFN-ß-1a groups. No other differences were evident between the local and systemic groups. CONCLUSIONS: IFN-ß-1a is effective in preventing epidural fibrosis with systemic and local application.

miR-216b Targets FGFR1 and Confers Sensitivity to Radiotherapy in Pancreatic Ductal Adenocarcinoma Patients Without EGFR or KRAS Mutation.

OBJECTIVES: The success of gemcitabine plus radiotherapy is dependent on the mutation status of pancreatic ductal adenocarcinoma (PDAC) tumors in the EGFR and KRAS genes; however, radiotherapy resistance may also be modulated epigenetically by microRNA (miRNA) regulation. In this study, we examined the potential effect of miRNAs on the resistance to radiotherapy in cases without EGFR or KRAS mutation. METHODS: The association of EGFR and KRAS mutation status and different expression patterns of 6 selected miRNAs related to the EGFR/KRAS signaling pathway were evaluated in the tumors of 42 patients with PDAC. RESULTS: Reduced miR-216b and miR-217 expression was associated with aggressive tumor characteristics and shortened disease-free survival. In addition, miR-216b expression was reduced 2.7-fold in the cases that did not benefit from therapy, although they did not demonstrate EGFR or KRAS expression (P = 0.0316). A negative correlation between FGFR1 and miR-216b expression (r = -0.355) was found in the tumors of these cases. CONCLUSIONS: Further studies and validations are required; in the tumors of patients with PDAC without activating mutations and induced expression of EGFR/KRAS genes, down-regulated miR-216b expression may be associated with a poor response to radiotherapy via deregulation of another signaling pathway related to FGFR1 signaling.