Docetaxel-induced pericardial effusion.

Hypersensitivity reactions, cumulative fluid retention, and neurotoxicity are frequently seen toxicities related to docetaxel. Fluid retention may be present as edema, weight gain, or third place fluid collection. Pericardial effusion is rarely seen with docetaxel treatment. We report a 58-year-old female patient who was presented with pericardial tamponade after three cycles of docetaxel therapy.

Breast cancer survivors suffer from persistent postmastectomy pain syndrome and posttraumatic stress disorder (ORTHUS study): a study of the palliative care working committee of the Turkish Oncology Group (TOG).

PURPOSE: Persistent postmastectomy pain syndrome (PMPS) is one of the most important disturbing symptoms. Posttraumatic stress disorder (PTSD) is an anxiety disorder which is characterized by reactions to reminders of the trauma that has been experienced. The purpose of this study is to evaluate the predictors of PMPS and PTSD in Turkish breast cancer survivors and the correlation between PMPS and PTSD. METHOD: The study is designed as a multicenter survey study. Breast cancer patients in remission were evaluated. Patients were evaluated with structured questionnaires to assess the PMPS and clinical parameters associated with it. The Turkish version of the posttraumatic stress disorder checklist-civilian version (PCL-C) was used. RESULTS: Between February 2015 and October 2015, 614 breast cancer survivors in outpatient clinics were evaluated. The incidence of PMPS documented is 45.1 %. In the multivariate analysis low income, presence of PTSD and <46 months after surgery were associated with increased risk of PMPS. PTSD was documented in 75 %, and the mean PCL-C score was 32.4 ± 11.1. PMPS and being married at the time of the evaluation were linked with PTSD. CONCLUSIONS: It is the first data about the association between PMPS and PTSD. The clinicians should be aware of PMPS and PTSD in breast cancer survivors.

Adjuvant Concurrent Chemoradiotherapy (CRT) plus Docetaxel-Cisplatin-Fluorouracil (DCF) versus CRT plus Fluorouracil-Folinic Acid (FUFA) in Stage III Gastric Cancer.

INTRODUCTION: Adjuvant chemoradiotherapy (CRT) is the optimal management strategy in resectable gastric cancer. There is a debate about the efficacy of more aggressive CRT plus chemotherapy regimens in adjuvant setting. This study aimed to compare the efficacy of adjuvant CRT plus docetaxel-cisplatin-fluorouracil (DCF) versus CRT plus fluorouracil-folinic acid (FUFA) in stage III gastric cancer. METHODS: Patients with a diagnosis of stage III gastric cancer treated with adjuvant therapy after curative resection were analyzed. Patients' disease characteristics and impacts of the regimens on median disease-free survival (DFS) and median overall survival (OS) were analyzed retrospectively. RESULTS: One hundred sixty-one patients (102 in FUFA arm and 59 in DCF arm) with a median age of 56.0 (29-79) were evaluated. In the DCF arm, there were more renal toxicities (31.6% vs 6.4% P < 0.001), emergency department admissions (64.9% vs 23.7%, P < 0.001), and dose reductions/treatment modifications in the DCF arm (51.6% vs 37.2, P < 0.001). The median follow-up was 23 months (1-124) in the FUFA arm and 26.0 months (1-77) in the DCF arm. The median DFS was 25.0 months (%95 CI, 12.7-37.2) in the DCF arm and 17.0 months (%95 CI, 2.6-31.3) in the FUFA arm, P = 0.66. The median OS was 28.0 months (%95 CI, 17.0-38.9) in the DCF arm and 25.0 months (%95 CI, 11.9-36.0) in the FUFA arm, P = 0.70. CONCLUSION: In conclusion, when compared with FUFA regimen, more aggressive therapy with DCF was more toxic and did not improve OS in adjuvant setting of stage III gastric cancer.

Lymphoproliferative disorders in individuals with chronic hepatitis B and C in the Turkish population.

The aims of this cohort study were to evaluate the association of malignant lymphoproliferative disorders in patients with chronic viral hepatitis and to compare the results with those in individuals with non-alcoholic fatty liver disease. A total of 3,873 patients with chronic liver disease who were seen consecutively in the Liver Disease Outpatient Clinic between January 2001 and July 2007 were assessed retrospectively. The frequency of malignant lymphoproliferative disorders including non-Hodgkin's lymphoma, Hodgkin's lymphoma, and chronic lymphocytic leukemia in these patients was investigated. Of the total, 1,999 patients had chronic hepatitis B infection (male/female: 1,226/773, mean age: 45.1 ± 13.2 years), 978 had chronic hepatitis C infection (male/female: 437/541, mean age: 53.8 ± 13.7 years), and the remaining 896 had non-alcoholic fatty liver disease (male/female: 450/446, mean age: 50.8 ± 11.2 years). A malignant lymphoproliferative disorder was identified in 13 patients (male/female: 9/4, mean age: 52.8 ± 16.8 years) with chronic viral hepatitis, while no case of malignant lymphoproliferative disorder was identified in individuals with non-alcoholic fatty liver disease (P = 0.048). Among the patients with malignant lymphoproliferative disorders, seven had chronic hepatitis B infection and six had chronic hepatitis C infection; 11 had non-Hodgkin's lymphoma and two had chronic lymphocytic leukemia. All non-Hodgkin's lymphoma cases were B-cell lymphoma. Based on the data obtained in this investigation, the association with malignant lymphoproliferative disorders in chronic viral hepatitis seems to be high as compared to that occurring in individuals with non-alcoholic fatty liver disease.

Aflibercept-related nasal septum perforation.

Hypertension, cytopenia and diarrhea are the most common side effects of aflibercept. Rarely thromboembolism, hemorrhage, fistulization and reversible posterior leukoencephalopathy have been reported. Here we report a patient experiencing nasal septum perforation during aflibercept therapy.

Lower folate levels in gastric cancer: is it a cause or a result?

Folate deficiency and its association with cancer have been studied in the literature, but its clinical impact is still unknown. Folate deficiency and its result on gastric cancer is a mysterious part of oncology, with ongoing studies hopefully clarifying its impact on gastric cancer management. Lee et al studied folate deficiency and its impact on staging and clinical results. Here we try to contribute to the field by expressing our own thoughts about the paper.

Osteogenesis imperfecta, pseudoachalasia, and gastric cancer.

Osteogenesis imperfecta (OI) is a rare, inherited skeletal disorder characterized by abnormalities of type 1 collagen. Malignancy is rarely reported in patients with OI and it was suggested that this disease can protect against cancer. Here, we report a 41-year-old woman with symptoms of achalasia where repeated treatment of pneumatic dilation and stent replacement was unsuccessful; therefore, surgery was performed. Pathology showed gastric adenocarcinoma unexpectedly. Chemotherapy was given after assessing dihydropyrimidine dehydrogenase (DPD) enzyme activity, which can be deficient in OI patients. This is the first report of gastric cancer mimicking achalasia in a patient with OI.

A potential link between endothelial function, cardiovascular risk, and metabolic syndrome in patients with Non-alcoholic fatty liver disease.

BACKGROUND: Asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of nitric oxide (NO) synthetase. Elevated ADMA reduces NO formation and is associated with endothelial dysfunction. The aims of this study were to evaluate endothelial function and the cardiovascular risk (CVR) profile in patients with non-alcoholic fatty liver disease (NAFLD), and to determine whether or not an association with metabolic syndrome (MS) increases these parameters. METHODS: A total of 100 consecutive patients with NAFLD, who were seen in Liver Disease Outpatient clinic and 45 age- and sex-matched controls were included. Endothelial function was evaluated based on the serum ADMA level measured using a validated ELISA kit (DLD Diagnostika GMBH, Hamburg, Germany) and flow-mediated vasodilatation (FMV) measured via high-resolution external ultrasonography. The CVR profile was calculated according to the Framingham equation. RESULTS: At baseline there weren't any significant differences in brachial artery diameter between the NAFLD and control groups (3.7 ± 0.6 mm vs. 3.6 ± 0.6 mm, respectively). FMV and flow-independent vasodilatation in response to sublingual nitroglycerin did not differ between the NAFLD and control groups (mean: 16% ± 9.4% vs. 17.9% ± 12.4%, and 21.4% ± 14% vs. 17.8% ± 11.3%, respectively, p > 0.05). No significant difference in the serum ADMA concentration between the NAFLD and control groups was observed (mean: 0.8 ± 0.07 µmol L(-1) vs. 0.74 ± 0.2 µmol L(-1), respectively). The CVR profile was significantly higher in the NAFLD group than in the control group (mean: 9% ± 6.9% vs. 4.6% ± 3.8%, P = 0.000). MS associated with NAFLD significantly increased the CVR profile (mean: 11.2% ± 7.4%, P = 0.000). An abnormal serum alanine aminotransferase level (>37 IU L(-1)) and the presence of fibrosis did not increase the CVR profile (p > 0.05). CONCLUSIONS: The risk of cardiovascular events is increased in patients with NAFLD. The association with MS is further increased such risk.

Genome-wide transcriptional reorganization associated with senescence-to-immortality switch during human hepatocellular carcinogenesis.

Senescence is a permanent proliferation arrest in response to cell stress such as DNA damage. It contributes strongly to tissue aging and serves as a major barrier against tumor development. Most tumor cells are believed to bypass the senescence barrier (become "immortal") by inactivating growth control genes such as TP53 and CDKN2A. They also reactivate telomerase reverse transcriptase. Senescence-to-immortality transition is accompanied by major phenotypic and biochemical changes mediated by genome-wide transcriptional modifications. This appears to happen during hepatocellular carcinoma (HCC) development in patients with liver cirrhosis, however, the accompanying transcriptional changes are virtually unknown. We investigated genome-wide transcriptional changes related to the senescence-to-immortality switch during hepatocellular carcinogenesis. Initially, we performed transcriptome analysis of senescent and immortal clones of Huh7 HCC cell line, and identified genes with significant differential expression to establish a senescence-related gene list. Through the analysis of senescence-related gene expression in different liver tissues we showed that cirrhosis and HCC display expression patterns compatible with senescent and immortal phenotypes, respectively; dysplasia being a transitional state. Gene set enrichment analysis revealed that cirrhosis/senescence-associated genes were preferentially expressed in non-tumor tissues, less malignant tumors, and differentiated or senescent cells. In contrast, HCC/immortality genes were up-regulated in tumor tissues, or more malignant tumors and progenitor cells. In HCC tumors and immortal cells genes involved in DNA repair, cell cycle, telomere extension and branched chain amino acid metabolism were up-regulated, whereas genes involved in cell signaling, as well as in drug, lipid, retinoid and glycolytic metabolism were down-regulated. Based on these distinctive gene expression features we developed a 15-gene hepatocellular immortality signature test that discriminated HCC from cirrhosis with high accuracy. Our findings demonstrate that senescence bypass plays a central role in hepatocellular carcinogenesis engendering systematic changes in the transcription of genes regulating DNA repair, proliferation, differentiation and metabolism.

Potential proteomic biomarkers in assessing liver fibrosis using SELDI-TOF MS.

BACKGROUND/AIMS: The accurate assessment of the severity of liver fibrosis is of paramount importance in determining treatment strategies, response to treatment and prognosis in patients with chronic liver disease. The aim of this study was to investigate potential proteomic biomarkers for assessing stages of hepatic fibrosis. METHODS: Serum samples of 83 patients with chronic liver disease (using METAVIR index, 17 F0, 30 F1, 6 F2, 9 F3, and 21 F4 patients) and 29 healthy controls were analyzed using surface-enhanced laser desorption/ionization time-of- flight mass spectrometry on IMAC30 ProteinChip arrays. Discriminatory peaks between groups were identified using Mann-Whitney U non-parametric test. Comparison of mild (F0, F1) and severe fibrosis (F2, F3, F4) was performed using tree classification (cross-validation) with the Biomarker Patterns Software, version 5.0 (Ciphergen Biosystems, US). RESULTS: No statistically significant discriminatory peak was evident between F0, F1 and F2 fibrosis. More than 30 peaks were found to be discriminatory between patients with cirrhosis (F4) and all other stages of liver fibrosis, including F2 and F3. Six surface-enhanced laser desorption/ionization proteomic features were found to be discriminative for mild (F0, F1) vs. advanced (F2, F3, F4) fibrosis (AUROC ≥0.8, p<0.05, Mann-Whitney test). The decision tree (m/z 4280, 10453 and 6376) yielded a sensitivity of 83.3% (30/36), a specificity of 85.1% (40/47), a positive predictive value of 81.1%, and a negative predictive value of 86.9%, with an AUROC of 0.94. CONCLUSIONS: The results of this study revealed discriminatory peaks between the protein profiles of patients with cirrhosis and other stages of liver fibrosis. Potential proteomic biomarkers can be notably determined for discriminating mild and advanced fibrosis using surface-enhanced laser desorption/ionization time-of- flight mass spectrometry.

Aflatoxin exposure in viral hepatitis patients in Turkey.

BACKGROUND/AIMS: Hepatocellular carcinoma is the fifth most common cancer and a major public health problem worldwide. Differences in distribution of hepatocellular carcinoma incidence are probably due to different levels of exposure to hepatocellular carcinoma risk factors: chronic infections with hepatitis B virus (HBV) and aflatoxin exposure in developing countries, and smoking and alcohol abuse in developed countries. Aflatoxin is one of the most important of the environmental toxins that contribute to the pathogenesis of hepatocellular carcinoma, especially in the regions where dietary foodstuffs (peanuts, corn, Brazil nuts, pistachios, spices and figs) are highly contaminated. High aflatoxin levels have been shown in the foodstuffs that are produced in our country. The specific aim of this study was to assess the rate of aflatoxin exposure and to determine some clues about aflatoxin metabolism by measuring and comparing the levels of carcinogenic forms in healthy subjects, in different stages of viral disease, and in different viral hepatitis types. METHODS: This was a cross-sectional observational, single-center study. A total of 203 (male/female: 119/84) viral hepatitis patients who were consecutively admitted to Ankara University, School of Medicine, Gastroenterology Clinic, between January 2006 and June 2007 were enrolled into the study. Sixty-two healthy subjects (male/female: 33/29) with normal blood chemistry and negative viral serology served as controls. Chemical forms AFB1, AFB2, AFG1, and AFG2 were assessed in plasma of study participants by high-performance liquid chromatography. RESULTS: AFB1, AFB2, AFG1, and AFG2 were detected in 24.6%, 17.2%, 22.7%, 18.2% of the 203 patients, respectively, and were significantly higher than in the control group for all chemical forms. Percentage of AFB1-positive patients was significantly higher than in the control group irrespective of disease stage. There was no significant difference between chronic infected patients, cirrhotic patients and patients with Hepatocellular carcinoma with respect to percentage of aflatoxin-positive individuals. CONCLUSIONS: With this study, we have documented that in viral hepatitis patients, aflatoxin exposure is significantly higher than in healthy subjects in Turkey and it may play an important role in the development of hepatocellular carcinoma. Thus, large studies exploring the relation between aflatoxin exposure, viral hepatitis status, and risk of hepatocellular carcinoma development are needed.

PPAR-alpha L162V polymorphism in human hepatocellular carcinoma.

BACKGROUND/AIMS: Several lines of evidence suggest that peroxisome proliferator-activated receptor alpha may be involved in hepatocarcinogenesis. L162V polymorphism of the peroxisome proliferator-activated receptor alpha gene enhances the transactivation activity of this transcription factor. The aim of this study was to determine the frequency and clinical correlates of peroxisome proliferator-activated receptor alpha L162V polymorphism in hepatitis virus-induced hepatocellular carcinoma. METHODS: 90 hepatocellular carcinoma patients diagnosed at Ankara University Gastroenterology Clinic between January 2002 and July 2003 and 80 healthy controls with normal body mass index, blood chemistry and with negative viral serology were included. peroxisome proliferator-activated receptor alpha L162V polymorphism was determined by PCR-RFLP. RESULTS: hepatocellular carcinoma etiologies were as follows: 56 HBV, 12 HBV+HDV, 22 HCV. Eighty-seven patients (97%) were cirrhotic, and 60 patients (67.5%) had advanced tumors. In 83 (92%) of 90 hepatocellular carcinoma patients, gene segment including polymorphic region could be amplified by PCR (50 HBV, 12 HBV+HDV, 21 HCV) and 6 of them (7.2%, all infected with HBV) had L162V polymorphism, while 2 (2.5%) of 80 controls had this polymorphism (p=0.162). This trend became more remarkable when only HBV (HBV+HDV)-infected patients were compared with controls (6/62, 9.7% vs. 2/80, 2.5%, respectively, p=0.071). Five of 6 patients with L162V had advanced disease. CONCLUSIONS: Peroxisome proliferator-activated receptor alpha L162V polymorphism tends to occur in HBV-induced hepatocellular carcinoma and is absent in HCV-related hepatocellular carcinoma. These findings may show clues for the existence of different carcinogenesis mechanisms in these two common etiologies. Frequent occurrence of advanced disease in patients with L162V polymorphism suggests a role for this polymorphism in tumor progression.