Evaluation of the relationship between atherosclerosis and Helicobacter pylori infection with measurement of growth differentiation factor 15 and atherosclerosis indicators in adults with no comorbidity / Evaluación de la relación entre aterosclerosis e infección por Helicobacter pylori con medición del factor de diferenciación de crecimiento 15 e indicadores de aterosclerosis en adultos sin comorbilidad

Background The aim of this study was to investigate presence of subclinical atherosclerosis by measuring carotid intima-media thickness (CIMT) in patients with Helicobacter pylori (HP) and to assess effects of HP on atherosclerosis by evaluating markers of atherosclerosis and blood growth differentiation factor (GDF-15) levels. Materials and methods This cross-sectional study included 59 patients without comorbid disease who had HP and 30 healthy controls without HP in upper endoscopic biopsy. In order to assess atherosclerosis, the CIMT measurement was performed by sonography. Serum GDF-15 level was measured by ELISA method. In all patients, atherosclerosis markers were recorded. Atherogenic indices were calculated, including Castelli risk index I and II (TG/HDL-c and LDL-c/HDL-c, respectively), plasma atherogenic index (PAI; log TG/HDL-c), non-HDL-c (TH-HDL-c) and atherogenic coefficient (AC; non-HDL-HDL-c). Results The GDF-15 level and CIMT were significantly higher in HP-positive group when compared to HP-negative group (p≤0.001). There was a significant correlation between serum GDF-15 level and CIMT (r=0.445; p≤0.001). There was no correlation between other atherosclerosis markers and serum GDF-15 level or CIMT. The bacterial intensity on endoscopic specimen was only correlated with CIMT (p<0.001). Vitamin B12 and D levels were comparable among groups. Conclusion This study suggested that there was a correlation between GDF-15 level and subclinical atherosclerosis development in patients with HP. However, GDF-15 level, which was found to be elevated while atherogenic indices were normal, can be an earlier marker for subclinical atherosclerosis. (AU)

Antecedentes El objetivo de este estudio fue investigar la presencia de aterosclerosis subclínica mediante la medición del grosor íntima-media de la carótida (GIMC) en pacientes con Helicobacter pylori y evaluar los efectos de H.pylori sobre la aterosclerosis mediante la evaluación de marcadores de aterosclerosis y de niveles de factor de diferenciación del crecimiento sanguíneo (growth differentiation factor 15 [GDF-15]). Materiales y métodos Este estudio transversal incluyó 59 pacientes sin enfermedad comórbida que tenían H.pylori y 30 controles sanos sin H.pylori en la biopsia endoscópica superior. Para evaluar la aterosclerosis, la medición de GIMC se realizó mediante ecografía. El nivel de GDF-15 en suero se midió mediante el método ELISA. En todos los pacientes se registraron marcadores de aterosclerosis. Se calcularon los índices aterogénicos, incluyendo el índice de riesgo de Castelli I y II (TG/cHDL y cLDL-cHDL, respectivamente), el índice aterogénico plasmático (PAI; log TG/HDL-c), no-cHDL (TH-cHDL) y el coeficiente aterogénico (no-HDL-cHDL). Resultados Los niveles de GDF-15 y de GIMC fueron significativamente más altos en el grupo H.pylori positivo en comparación con el grupo H.pylori negativo (p≤0,001). Hubo una fuerte correlación entre el nivel sérico de GDF-15 y el GIMC (r=0,445; p≤0,001). No hubo correlación entre otros marcadores de aterosclerosis y el nivel sérico de GDF-15 o GIMC. La intensidad bacteriana en la muestra endoscópica solo se correlacionó con GIMC (p≤0,001). Los niveles de vitaminaB12 y de vitaminaD fueron comparables entre los grupos. Conclusión Este estudio sugirió que había una correlación entre el nivel de GDF-15 y el desarrollo de aterosclerosis subclínica en pacientes con H.pylori. Sin embargo, el nivel de GDF-15, que se encontró elevado mientras que los índices aterogénicos eran normales, puede ser un marcador temprano de aterosclerosis subclínica. (AU)

The prognostic and predictive role of class III ß-Tubulin and hENT1 expression in patients with advanced pancreatic ductal adenocarcinoma.

BACKGROUND: FOLFIRINOX and gemcitabine-nabpaclitaxel (GnP) are standard first-line treatment regimens for advanced pancreatic ductal adenocarcinoma (PDAC). However, currently, there is a lack of predictive biomarkers to aid in the treatment selection. We aimed to explore the prognostic and predictive value of class III ß-Tubulin (TUBB3) and human equilibrative nucleoside transporter 1 (hENT1) expression, which have previously been shown to be associated with taxane and gemcitabine resistance in advanced PDAC. METHODS: We conducted a retrospective analysis of 106 patients with advanced PDAC treated with GnP and/or FOLFIRINOX at our institution. TUBB3 and hENT1 immunohistochemical staining was performed on tumor specimens and subsequently evaluated based on the intensity and percentage of expression. RESULTS: In patients who received the GnP regimen, a high combined score (TUBB3low/hENT1high) was associated with a higher DCR and longer PFS compared to those with intermediate (TUBB3high/hENT1high or TUBB3low/hENT1low) and low score (TUBB3high/hENT1low). In the multivariate analysis, a high combined score was an independent predictor of higher DCR (OR:11.96; 95 % CI:2.61-54.82; p = 0.001) and longer PFS (HR:0.33; 95%CI:0.18-0.60; p < 0.001). However, there was no difference in response rates or PFS based on TUBB3 and hENT1 expression among patients receiving the FOLFIRINOX regimen. CONCLUSION: Our findings indicate that tumor TUBB3 and hENT1 expression may predict the efficacy of the GnP regimen, and low TUBB3 and high hENT1 expression (TUBB3low/hENT1high) are associated with a higher DCR and longer PFS in patients treated with GnP. Evaluating TUBB3 and hENT1 jointly can identify the patients most (as well as least) likely to benefit from GnP chemotherapy.

PILE: a candidate prognostic score in cancer patients treated with immunotherapy

Background Although the immune checkpoint inhibitors (ICIs) became a vital part of cancer care, many patients do not respond to treatment, indicating need for biomarkers. The Pan-Immune-Inflammation Value (PIV) is a recently developed peripheral blood count-based biomarker. Herein, we evaluated a PIV-based candidate scoring system as a prognostic biomarker in ICI-treated patients. Methods A total of 120 advanced cancer patients treated with anti-PD-1 or anti-PD-L1 inhibitors for any cancer type were included in this study. The PILE scoring system incorporating the PIV (< median vs. ≥ median), lactate dehydrogenase levels (normal vs. > normal) and Eastern Cooperative Oncology Group performance status (0 vs. ≥ 1) was constructed from the multivariate analyses and used for stratification. The association between overall survival (OS), progression-free survival and PILE risk category was evaluated with multivariate analysis. Results The median follow-up was 9.62 months and the median OS of all cohort were 12.42 ± 2.75 months. Patients with higher PIV had significantly decreased OS (7.75 ± 1.64 vs. 18.63 ± 4.26 months, p = 0.037). The patients in the PILE high-risk group (PILE score 2–3) had decreased OS (18.63 ± 4.02 vs. 5.09 ± 1.23 months, HR: 2.317, 95% CI: 1.450–3.700, p < 0.001) and PFS (7.69 ± 1.30 vs. 2.69 ± 0.65 months, HR: 1.931, 95% CI: 1.263–2.954, p = 0.002) compared to PILE low-risk group (PILE score 0–1). The Harrell C-Index values were 0.65 and 0.61 for OS and PFS prediction, respectively. Conclusion In this study, we demonstrated a decreased overall survival in ICI-treated patients with a higher PILE score. If prospective studies validate our results, PILE score could be a biomarker for immunotherapy. (AU)

The expression and relationship of AdipoR1/R2 in gastric intestinal metaplasia.

BACKGROUND: Adiponectin (ApN) is a 244-amino acid protein mainly secreted from the adipose tissue and involved in various physiological functions. ApN exerts its metabolic effects by binding to two major receptors: adiponectin receptor-1 (Adipo-R1) and adiponectin receptor-2 (Adipo-R2). Recent studies have reported ApN's involvement in the progression of cancer. However, there are no studies evaluating the relationship between Adipo-R1/R2 expression and gastric intestinal metaplasia (IM), which is a predisposing factor in gastric cancer (GC) development, and Helicobacter pylori H. pylori infection. AIMS: In this study we aimed to investigate the relationship between the Adipo-R1/-R2 expression and H. pylori infection in patients with GC and gastric IM. MATERIALS AND METHODS: Forty patients that underwent gastric resection and 56 patients that developed gastric IM were included in the study. The Adipo-R1/-R2 expression and the presence of H. pylori were examined immunohistochemically. The univariate analyses showed that the expression of Adipo-R1/-R2 in GC patients was significantly lower compared to both complete metaplasia (CM) and incomplete metaplasia (ICM) patients (p <0.0001 for both). RESULTS: According to multiple multinomial logistic regression analysis, Adipo-R1/-R2 expression in the CM group was significantly higher than in the GC group (p = 0.05, p = 0.014, respectively). Moreover, Adipo-R1/-R2 expression was significantly higher in ICM group compared to the GC group (p=0.012, p=0.045, respectively). However, in both analyses no significant difference was determined in terms of H. pylori positivity between the groups. CONCLUSION: The resulting data suggests that ApN plays a role in GC processes via Adipo-R1/-R2 receptors.

PILE: a candidate prognostic score in cancer patients treated with immunotherapy.

BACKGROUND: Although the immune checkpoint inhibitors (ICIs) became a vital part of cancer care, many patients do not respond to treatment, indicating need for biomarkers. The Pan-Immune-Inflammation Value (PIV) is a recently developed peripheral blood count-based biomarker. Herein, we evaluated a PIV-based candidate scoring system as a prognostic biomarker in ICI-treated patients. METHODS: A total of 120 advanced cancer patients treated with anti-PD-1 or anti-PD-L1 inhibitors for any cancer type were included in this study. The PILE scoring system incorporating the PIV (< median vs. ≥ median), lactate dehydrogenase levels (normal vs. > normal) and Eastern Cooperative Oncology Group performance status (0 vs. ≥ 1) was constructed from the multivariate analyses and used for stratification. The association between overall survival (OS), progression-free survival and PILE risk category was evaluated with multivariate analysis. RESULTS: The median follow-up was 9.62 months and the median OS of all cohort were 12.42 ± 2.75 months. Patients with higher PIV had significantly decreased OS (7.75 ± 1.64 vs. 18.63 ± 4.26 months, p = 0.037). The patients in the PILE high-risk group (PILE score 2-3) had decreased OS (18.63 ± 4.02 vs. 5.09 ± 1.23 months, HR: 2.317, 95% CI: 1.450-3.700, p < 0.001) and PFS (7.69 ± 1.30 vs. 2.69 ± 0.65 months, HR: 1.931, 95% CI: 1.263-2.954, p = 0.002) compared to PILE low-risk group (PILE score 0-1). The Harrell C-Index values were 0.65 and 0.61 for OS and PFS prediction, respectively. CONCLUSION: In this study, we demonstrated a decreased overall survival in ICI-treated patients with a higher PILE score. If prospective studies validate our results, PILE score could be a biomarker for immunotherapy.

Prognostic factors and treatment of patients with advanced synovial sarcoma: A single-center experience.

BACKGROUND: Synovial sarcoma (SS) is a malignant mesenchymal tumor, which comprises 5%-10% of all the sarcomas. There is insufficient information on prognostic factors and salvage treatments of advanced SS. In this study, we aimed to further clarify the clinicopathological features, prognostic factors, and treatment modalities in advanced SS. MATERIALS AND METHODS: A total of 45 SS patients followed up between 2001 and 2015 at our cancer institute, Department of Medical Oncology, were retrospectively evaluated. Eleven patients were initially metastatic, and remaining patients developed metastasis or became inoperable due to locally advanced disease. Overall survival was evaluated by Kaplan-Meier analysis. RESULTS: The median age of patients was 37 (17-70) years and 60% (n = 26) of them were female. SS was most commonly localized in the lower extremity and abdomen-pelvis (29% and 29%, respectively). Median follow-up time was 33 (6-175) months. Patients were treated with a median of two (1-5) line chemotherapies at metastatic stage. Ifosfamide plus adriamycin (IMA) (49%, n = 22) and cisplatin-etoposide (13%, n = 6) were the most often used chemotherapy regimen as first line in metastatic stage. Partial response was obtained in 32% of the patients treated with IMA chemotherapy. Furthermore, median progression-free survival was 6 (1-123) months. Median survival of metastatic stage at diagnosis or in follow-up was 21 months (14-27) and 21 (12-29) months (P = 0.53), respectively. Most metastatic locations were lung (75%) and bone. Factors influencing survival at metastatic stage were evaluated; statistically significant longer survival was observed in patients with lung metastasis, primary tumor size smaller than 10 cm, patients who underwent surgery for the metastasis, and development-to-metastasis period longer than 12 months. CONCLUSION: Median survival of patients in metastatic stage SS was 21 months. Lung was the most common metastatic site.

The prevalence of usage of herbal medicines among cancer patients.

PURPOSE: To study the prevalence of the usage of herbal medicines among cancer patients. METHODS: This study was carried out between October 1, 2009 and May 31, 2011, by using face-to-face interviews with cancer patients attending oncology departments (clinics and outpatient clinics, chemotherapy units). A special questionnaire was filled in during the interviews. RESULTS: Of the patients 68.2% reported usage of herbal medicines, 66% stated that their usage of herbal medicines was based on the media and the Internet as a source and 64% stated that they received information about herbal medicines from relatives and friends. Only 24% of herbal medicines users had consulted or discussed their use with a physician. CONCLUSION: In Turkey, especially among cancer patients, there is a high prevalence of complementary and alternative medicine (CAM) usage and the most commonly used form of CAM is herbal medicines. This prevalence has also been found to be high in our research as well. Due to the probable side effects and potential drug interactions of herbal agents, all cancer patients should be asked about their use of herbal medicines.

Breast cancer in octogenarian women: clinical characteristics and outcome.

PURPOSE: Breast cancer incidence increases in the elderly but data on treatment and outcomes of elderly patients is limited. We assessed the clinicopathological features and outcomes of our patients with breast cancer aged ≥80 years in comparison with their younger postmenopausal counterparts. METHODS: The records of 83 patients diagnosed with breast cancer after the age of 80 (group 1) between 2003 and 2011 in 4 different centers were retrospectively evaluated and the clinicopathological features and outcomes were assessed in comparison with a control group (group 2) of 249 patients aged between 60-70 years. RESULTS: Median ages at diagnosis were 82 years (range 80-95) and 64 years (range 60-70) for group 1 and group 2, respectively. The incidence of invasive cancers other than ductal or lobular type was higher in group 1 than in group 2 (20 vs 8%; p=0.0177rpar;. More patients in group 1 had Charlson Comorbidty scores ≥1 than those in group 2 (49 vs 36%; p=0.011). Patients in group 1 had more conservative operations and less axillary node dissections (ALND) and they received chemotherapy, trastuzumab or radiotherapy less frequently compared to their younger counterparts in group 2. Median follow up period was 36 months (range 1-178) in group 1 and 24 months (range 12-217) in group 2. Five-year disease free survival (DFS) was 53.7 and 75.9) (p=0.005), 5-year overall survival (OS) was 61.9% and 80.47percnt; in group 1 and group 2 (p=0.001), respectively. Advanced stage (stage IV vs stage I, II, III, p=0.051) and cerbB2 positivity (p<0.001) were found to be associated with shorter DFS in patients ≥80 years of age. CONCLUSION: Although the majority of patients were undertreated in our study according to the current guidelines, mortality rates were quite low. Different biology of the disease in the elderly might explain this difference.

Trabectedin in advanced soft tissue sarcoma: case series.

The prognosis of advanced soft tissue sarcomas (STS) is poor. The median overall survival (OS) is 6 months in unresectable and metastatic STS that progress after treatment with anthracyclines and ifosfamide. Trabectedin is an alkylating agent, effective in advanced STS, especially in leiomyosarcoma and liposarcoma. In the present study, the effectiveness and safety of trabectedin was retrospectively evaluated in 8 unresectable and metastatic STS patients. Their median age was 47 years. The median progression free survival (PFS) was 3.75 months and the median OS 15 months in relapse or progression after anthracyclines and/or ifosfamide. Toxicities were mainly hematologic. In the present study, trabectedin showed efficacy in different histological subtypes of sarcomas like liposarcoma and leiomyosarcoma.

Pure mucinous carcinoma of the breast: a single center experience.

PURPOSE: Mucinous breast carcinoma is rare subtype of breast cancer. Histopathologically, it is classified into two forms, pure and mixed type. It recurs late, metastasis to axillary lymph nodes is less common and is more hormone receptor positive. We herein present the data of our patients with pure mucinous breast cancer (PMBC) treated in our institution. METHODS: Among 1211 breast cancer patients with breast cancer diagnosed and treated in Hacettepe University Institute of Oncology, 20 patients (1.6%) with PMBC (defined as having mucinous component of more than 90%) were identified. Patient demographics, tumor characteristics and patient outcomes were assessed retrospectively. RESULTS: The median age at diagnosis was 52.5 years (range 27-80). The majority of the patients presented with stage II disease (n=15; 75%). One of 20 patients recurred with bone metastasis 50 months after diagnosis. Median follow-up was 39 months (range 3-137). Estrogen receptors (ER) were positive in 16 (80%) patients and HER-2 positive in one (5%). Twenty-five percent of the patients had positive axillary nodes. CONCLUSION: PMBC is a rare entity with favorable prognosis. Lymph node metastasis is rarely seen even in large -sized tumors.

Malignancies after rituximab treatment: just coincidence or more?

PURPOSE: Rituximab has been successfully used in the treatment of B-cell non-Hodgkin's lymphoma (NHL) and some autoimmune diseases nearly for a decade. Several other malignancies and CD20-negative lymphomas have been reported in the literature after rituximab treatment. We aimed to investigate whether there is an association between rituximab treatment and the development of second malignancies. METHODS: A detailed search in English language literature on reports about rituximab treatment and secondary malignancies was made through Medline. The papers were reviewed and the cases were summarized according to secondary tumor types, intervals between rituximab treatment and second malignancy occurrence, indications for rituximab treatment and cytotoxic chemotherapy administration. RESULTS: There were 26 previously reported cases of CD20-negative lymphoma and solid tumors after rituximab treatment. The median age of these cases was 62 years (range 34-80). The median time period from the initiation of rituximab treatment to diagnosis of second malignancies was 5 months (range 1-40). The most frequently reported solid tumors were skin tumors (squamous cell carcinoma and Merkel cell carcinoma) (n=7; 27%), CD20-negative lymphomas (n=5; 20%), Kaposi sarcoma (n=4; 15%), and others (n=10; 38%). CONCLUSION: Association between rituximab and subsequent development of second malignancies might be a coincidence. However, we suggest close monitoring for second malignancies, particularly skin tumors, in patients treated with rituximab. This issue should be evaluated in further studies.