Genotoxic and genoprotective effects of some antipsychotic drugs, methylphenidate and atomoxetine on human lymphocytes and HepG2 cells.

OBJECTIVE: Aripiprazole, risperidone, atomoxetine, and methylphenidate are drugs commonly prescribed for many psychiatric conditions and can be used alone or in combination in children and adolescents. This study aimed to investigate comparatively the possible genotoxic effects or genoprotective potentials of these drugs on human lymphocytes and HepG2 cells. MATERIALS AND METHODS: Cytotoxicity analysis was performed with the cell viability test on human lymphocytes and HepG2 cells, and half-maximal inhibitory concentration (IC50) values of the drugs were determined, and three different doses (» IC50, ½ IC50, and IC50) were applied for genetic analysis. For the determined doses, cells with and without DNA damage were examined by comet analysis. RESULTS: In lymphocytes, aripiprazole and risperidone increased DNA damage at moderate and maximum doses, whereas atomoxetine increased DNA damage only at the maximum dose. In HepG2 cells, risperidone reduced DNA damage at all doses, while atomoxetine increased DNA damage at all doses. On the other hand, in the DNA-damaged cells induced by hydrogen peroxide (H2O2), DNA damage decreased at all concentrations of all drugs in both lymphocytes and HepG2 cells. CONCLUSIONS: As a result, the genotoxicity of the drugs was found to be dose-dependent, and all drugs showed a genoprotective effect on DNA-damaged cells.

The relationship between microsatellite instability in colorectal adenocarcinoma and tumor budding and histopathological parameters.

OBJECTIVE: This study aims to investigate the correlation between the presence of microsatellite instability (MSI) and tumor budding, as well as their relationship with histopathological parameters in patients diagnosed with colorectal adenocarcinoma. PATIENTS AND METHODS: The study encompassed patients who underwent curative surgery to treat colorectal cancer. These patients were classified into groups based on their MSI status. The International Tumor Budding Consensus Conference (ITBCC) 2016 guidelines were utilized to identify tumor budding. Demographics, clinical data, tumor budding, and histopathological attributes were assessed across study groups. RESULTS: The study analyzed 268 patients, out of which 32 (11.9%) were identified as having MSI. Microsatellite Stable (MSS) patients were placed in Group 1, and those with MSI were classified into Group 2. The average age was lower in Group 2 compared to Group 1 (55.9 years vs. 61.4 years, p=0.034). Tumor localizations in the caecum (5.9% vs. 18%) and the ascending colon (11.9% vs. 25%) were more prevalent in Group 2 (p=0.019). The occurrence of tumor budding (75% vs. 62.5%, p=0.133) and the budding degree in those with tumor budding were comparable between the groups. Poorly differentiated tumors were more prevalent in Group 2 (5.5% vs. 25%, p=0.001). Additionally, the tumor diameter was larger in Group 2 (3.58 cm vs. 4.35 cm, p=0.007). CONCLUSIONS: MSI is a significant biomarker, possessing diagnostic, prognostic, and predictive value in colorectal cancer (CRC). Understanding the connection between MSI and tumor budding in CRC may provide clinicians with insights to enhance patient management.

Impact of radiologic variables on item responses of ODI, SRS22 and SF-36. in adult spinal deformity patients: differential item functioning (DIF) analysis results from a multi-center database.

PURPOSE: To determine if responses given to each question of the Scoliosis Research Society-22 (SRS22), Oswestry disability index (ODI) and Short Form-36 (SF-36) questionnaires are influenced by the radiological parameters. METHODS: Patients enrolled in a multi-centre prospectively collected adult spinal deformity database who had complete SRS22, ODI and SF-36 data at baseline and at one-year follow-up were analysed. The presence of a differential item function of each question within each score in relation to radiological parameters was analysed using a mixed Rasch model with the radiological threshold value(s) determined. RESULTS: Of those patients analysed (n = 1745; 1406 female, average age 51.0 ± 19.8 years), 944 were surgically and 801 were non-surgically treated. For the SRS22, questions (Q) 3, 5 and 18 were sensitive to almost all radiological parameters and the overall score was found sensitive to the Cobb angle. For the ODI, Q3, 6, 9 and 10 were not sensitive to any radiologic parameters whereas Q4 and 5 were sensitive to most. In contrast, only 3 of the SF-36 items were sensitive to radiological parameters. CONCLUSIONS: 78% of the SRS-22, 60% of the ODI and 8% of the questions in the SF-36 are sensitive to radiological parameters. Sagittal imbalance is independently associated with a poor overall outcome, but affects mental status and function more than pain and self-image. The assembly of questions responsive to radiological parameters may be useful in establishing a connection between changes in radiologic parameters and HRQL.

Efficacy of combination of biofeedback therapy and pelvic floor muscle training in dyssynergic defecation.

BACKGROUND: It is now known that with appropriate exercises, the functions of the muscles in the body ameliorate and increase in strength. We applied pelvic floor muscle relaxation training and exercises that strengthen the abdominal and pelvic muscles in combination with biofeedback therapy (BFT) to patients with dyssynergic defecation (DD). METHODS: Patients who met the criteria for DD and had no underlying organic cause were included in this study. The electromyography (EMG) technique was used for BFT therapy. Patients had received at least six sessions of BFT. BFT was considered successful in patients when the DD pattern in anorectal manometry (ARM) disappeared and/or adequate anal relaxation was obtained following BFT and in patients who had full clinical recovery. RESULTS: Data of 104 patients (58 females [55.8%] and 46 males [44.2%]) was evaluated. Abdominal and rectal symptoms disappeared in 71 (68.26%) patients. Of the patients who achieved symptomatic improvement, 58 (55.76%) saw a disappearance of the dyssynergic defecation pattern. When the differences between anal sphincter pressures before and after treatment were compared in patients who responded to BFT and those who did not, no significant differences were observed, but significant changes were found in anal squeezing pressures. It was found that those who had high squeezing pressures before BFT, those who increased their squeezing pressures after BFT, and those who decreased their resting pressure responded better to BFT. CONCLUSIONS: In this study, BFT was found to be more effective in those with a high squeezing pressure and those that increased squeezing pressure after BFT. These findings will influence the treatment of patients with dyssynergic defecation who do not respond to treatment. A combination of abdominal and pelvic floor muscle exercises and BFT increases patient response.

The therapeutic effect of Cilastatin on drug-induced nephrotoxicity: a new perspective.

OBJECTIVE: By creating nephrotoxicity models with cisplatin, vancomycin, and gentamicin in HK-2 (human renal proximal tubule cell) and HEK293T (human embryonic kidney epithelial cells) cell lines, we aimed to evaluate the effect of cilastatin on recovery of cell damage after toxicity had occurred. MATERIALS AND METHODS: In the first phase of the study, the doses of cisplatin, vancomycin, and gentamicin (50% inhibitive concentration; IC50) were determined. In the second phase, the effective dose of cilastatin against these drugs was determined, and IC50 doses of nephrotoxic agents were administered simultaneously. In the third phase of our study, to evaluate the possible therapeutic effect of cilastatin after toxicity had occurred, the analyses of cell viability, apoptosis, oxidative stress, expression of kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) were performed. RESULTS: In the second phase of the study, it was observed that cilastatin increased cell viability when treated simultaneously with a nephrotoxic agent. In the third phase, cilastatin provided a significant increase in cell viability. After treatment with each agent for 24 hours, we determined that adding cilastatin to the medium had an effect on the recovery of cell damage by increasing cell viability and reducing apoptosis and oxidative stress. The expression of KIM-1 and NGAL increased when nephrotoxicity occurred and decreased with the addition of cilastatin to the medium. CONCLUSIONS: The findings of the study suggest that cilastatin may have a healing effect after the development of nephrotoxicity.

Acanthosis nigricans: a warning sign of lower urinary tract dysfunction in obese children?

OBJECTIVE: There have been very few studies on the relationship between lower urinary tract dysfunction (LUTD) and obesity-related metabolic disorders in the pediatric age group. This study investigated the relationship between LUTD and metabolic disturbances in obese children. PATIENTS AND METHODS: Four-hundred obese children (body mass index ≥ 95th percentile) were included in the present study. Anthropometric, clinical, and biochemical parameters were evaluated. The Dysfunctional Voiding and Incontinence Scoring System (DVISS) questionnaire was administered and scores over 8.5 were considered to be reflective of LUTD. Subjects were stratified into two groups based on DVISS symptom scores - obese children with and without LUTD. The homeostasis assessment model was used to evaluate insulin resistance and the International Diabetes Federation criteria to identify metabolic syndrome. RESULTS: Lower urinary tract dysfunction was detected in 19% of the study population. There were no significant differences between the two groups in terms of laboratory results. No statistically significant relationship was found between LUTD and the presence of metabolic syndrome or insulin resistance; however, a significant association was observed between LUTD and acanthosis nigricans. Regression analysis revealed that only the presence of acanthosis nigricans significantly increased the risk of lower urinary tract dysfunction by 1.75-fold (p < 0.05). CONCLUSIONS: The presence of acanthosis nigricans in obese children may suggest the concurrent occurrence of lower urinary tract dysfunction and should be investigated accordingly.

Assessment of serum levels of copeptin and corticotropin-releasing factor in children with monosymptomatic and non-monosymptomatic nocturnal enuresis.

BACKGROUND: Nocturnal enuresis is defined as bed-wetting in children from the age of five years that occurs during sleep; if untreated, the condition can result in social and psychological problems both for the children and their parents. Nocturnal enuresis is a complicated disease that includes multiple pathogenetic factors. Nocturnal enuresis is divided into two subgroups: monosymptomatic and non-monosymptomatic. The role of some biomarkers in patients with monosymptomatic enuresis has been reported in a small number of the studies. OBJECTIVE: The aim of this research was to evaluate the serum levels of copeptin and corticotropin-releasing factor (CRF) in monosymptomatic and non-monosymptomatic nocturnal enuresis cases. Although these markers were previously examined in children with monosymptomatic enuresis, there is no study that has evaluated these markers in non-monosymptomatic children. STUDY DESIGN: One hundred nineteen children with nocturnal enuresis (5-16 years) and forty healthy children (5-17 years) were enrolled to the study. Of the nocturnal enuresis group, forty-nine were monosymptomatic and seventy were non-monosymptomatic. Copeptin and CRF were measured by a competitive inhibition method with enzyme-linked immunosorbent assay. RESULTS: The serum copeptin levels were significantly lower in children with monosymptomatic and non-monosymptomatic nocturnal enuresis than in the controls.(median, 34.7 [interquartile range (IQR): 34 pg/ml], 39.8 [IQR: 29 pg/ml] vs 52.1 [IQR: 14 pg/ml], respectively, P < 0.05). The serum CRF levels were significantly lower in children with monosymptomatic and non-monosymptomatic nocturnal enuresis than in the controls (median, 35.1 [IQR: 19 pg/ml], 34.05 [IQR: 24 pg/ml] vs 78.3 [IQR: 39 pg/ml], respectively, P < 0.05). There was no significant difference in copeptin and CRF levels between the children with monosymptomatic and non-monosymptomatic nocturnal enuresis. DISCUSSION: Copeptin is presumed to be a sensitive surrogate biomarker for arginine vasopressin release. To date, there are only two studies in the literature that assess the relationship between copeptin and monosymptomatic enuresis. The only study in the literature demonstrated significantly decreased levels of CRF in monosymptomatic enuretic children. It was demonstrated that the levels of copeptin and CRF differ in both children with monosymptomatic and non-monosymptomatic nocturnal enuresis from the control groups. It was also demonstrated that copeptin and CRF levels were not different between the children in monosymptomatic and non-monosymptomatic groups. CONCLUSION: Those changes in both copeptin and CRF which were shown in this study in monosymptomatic and non-monosymptomatic enuretic children may contribute to the pathogenesis of nocturnal enuresis. Further case-control studies can evaluate the copeptin and CRF levels before treatments in monosymptomatic and non-monosymptomatic patients to decide potential effectiveness of treatment.

Tunnel widening after single- versus double-bundle anterior cruciate ligament reconstruction: a randomized 8-year follow-up study.

OBJECTIVE: The purpose of this study was to compare the single-bundle (SB) and double-bundle (DB) surgical techniques for anterior cruciate ligament (ACL) reconstruction with regard to tunnel widening, isokinetic muscle strength, and clinical outcomes over an 8-year follow-up period. METHODS: This study included 31 patients with ACL injury who underwent ACL reconstruction via the SB (n = 16) or the DB (n = 15) technique. Isokinetic and concentric strength measurements of the quadriceps and hamstring muscles were conducted at postoperative 6 months and postoperative 8 years, and 3D-CT scans of the knee joints were performed on the 2nd, 3rd and 6th month, and the 8th year postoperatively. Clinical evaluations were performed at 8 years postoperatively with the International Knee Documentation Committee (IKDC), Tegner, and Lysholm knee scoring systems. RESULTS: There was marked widening of the parts of the femoral tunnel close to the knee joint in both the SD and the DB groups. There was no difference between the two groups in terms of clinical results and isometric muscle strength at postoperative 8 years; however, there was a significant difference between the preoperative and 6 months postoperative clinical and strength results in both group (P < 0.05). There was no difference between the groups in IKDC score, Lysholm score, Tegner activity scale, and anterior drawer test at postoperative 8 years. On evaluation of the anteromedial bundles alone, the DB group had greater widening than the SB group. CONCLUSION: In this study, we have found that the tunnels continue to enlarge after 6 months. However, that has no impact in patients comfort and that did not made any change in our daily routine. On the other hand, we found that the reconstruction of the double-band ligament technique is useless for non-professional athletes.

Protective effect of thymoquinone against cyclophosphamide-induced genotoxic damage in human lymphocytes.

OBJECTIVE: Protective effect of thymoquinone (TQ) against the cytotoxic and genotoxic effects of cyclophosphamide (CP) was assessed in human peripheral blood lymphocyte culture. METHODS: Mitotic indices were determined as endpoints of cytotoxicity, while sister chromatid exchanges (SCE) served as endpoints of genotoxicity. Firstly, the genotoxic effect of 0.16 µg/ml of CP was tested and CP was detected as genotoxic. In the second set, CP group was treated with 20 µM and 40 µM TQ. RESULTS: TQ reduced the SCE frequencies, suggesting its protective action on human lymphocytes in vitro against the CP induced genotoxic damage. CONCLUSIONS: Our results suggest that TQ produces a protective mechanism against CP-induced genetic damage, and suggest a role of DNA strand breaks in the genotoxicity (Tab. 1, Fig. 1, Ref. 19).

Using PVA and TPGS as combined emulsifier in nanoprecipitation method improves characteristics and anticancer activity of ibuprofen loaded PLGA nanoparticles.

In the preparation of nanoparticles (NPs) by the nanoprecipitation method, emulsifiers play a key role for NPs' characteristics. The present study aimed to investigate the combined emulsifier effect on ibuprofen loaded poly(lactic-co-glycolic acid) (PLGA) NPs' characteristics and anticancer activity. Ibuprofen loaded PLGA NPs were prepared by nanoprecipitation using different concentrations of PVA (poly(vinyl alcohol)) or PVA-TPGS (d-α-tocopherol polyethylene glycol 1000 succinate) combination as emulsifier. It was found that encapsulation efficiencies of NPs varied between 17.9 and 41.9 % and the highest encapsulation efficiency was obtained with 0.5% PVA + 0.1% TPGS (coded as PLGA PVA/TPGS NPs). PLGA PVA/TPGS NPs were characterized and compared with PLGA PVA NPs, which was obtained by 0.5% PVA alone. Polydispersity index of PLGA PVA/TPGS and PLGA PVA NPs were found to be 0.08 and 0.15, respectively. Incorporation of TPGS with PVA slightly decreased the initial ibuprofen release. Transmission electron microscopy analyses demonstrated a nearly uniform particle size distribution and spherical particle shape of the PLGA PVA/TPGS NPs. Additionally, PLGA PVA/TPGS NPs were significantly more cytotoxic than PLGA PVA NPs on the MCF-7 (human breast adenocarcinoma cells) and Caco-2 (human epithelial colorectal adenocarcinoma) cells (p<0.05). Also PLGA PVA/TPGS NPs were not cytotoxic on normal cells (L929, mouse healthy fibroblast cells) (p>0.05). In conclusion, these results indicated that using a combination of TPGS and PVA as an emulsifier in nanoprecipitation could be a promising approach for preparing ibuprofen loaded PLGA NPs because of their improved characteristics and anticancer activity.

The efficacy and safety of capecitabine plus bevacizumab combination as first-line treatment in elderly metastatic colorectal cancer patients

Aim: The optimal treatment in older persons with metastatic colorectal cancer (mCRC) is complicated by a lack of general agreement. The aim of this study was to evaluate the activity of bevacizumab plus capecitabine combination in elderly mCRC patients who were not suitable for chemotherapy with irinotecan and oxaliplatin-containing regimens. Materials and methods: Seventy years and older patients with metastatic colorectal carcinoma were included in this retrospective study. Bevacizumab was administered at a dose of 7.5 mg/kg on day 1 as an intravenous (IV) infusion over 30-90 min every 21 days, and capecitabine was prescribed at 1000 mg/m2 twice daily on days 1-14 of the same 21-day schedule. Results: Eighty-two consecutive patients (47 men, 35 women) were included in the study. The mean age was 75.5 (SD 3.9, range 70-87). Half of the patients were older than 75 years. There were 55 patients (67.1 %) with a good Eastern Cooperative Oncology Group (ECOG) performance status (PS: 0-1) and the remaining 27 patients (32.9 %) had a poor ECOG performance status (PS: 2). With a median follow-up period of 18.5 months, the median progression-free survival (PFS) was 10 months (95 % CI, 7.8-12.1) and the median OS was 25 months (95 % CI, 18.6-31.3). The main toxicities recorded were non-hematological. Thirty-one patients (37 %) experienced grade 3/4 adverse events, the most common being hand–foot syndrome (9.8 %). No fatal toxicity resulting from this regimen was recorded. Conclusions: Considering the toxicity profile and survival outcomes, the combination regimen of capecitabine and bevacizumab is a potentially feasible treatment option in elderly mCRC patients (AU)

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A CASE OF CONFINED PLACENTAL MOSAICISM WITH TRISOMY 15 ASSOCIATED WITH TURNER SYNDROME.

We here present a rare case of a Turner syndrome with mosaic trisomy 15 identified on chorionic villous sampling (CVS). Although there are several reports in the literature indicating confined placental mosaicism (CPM), counseling parents of a fetus with trisomy 15 mosaicism at CVS remains difficult because of the phenotypic variability. To illuminate that condition an amniocentesis or cord blood study should be offered in conjunction with genetic counseling.

Primary mucinous carcinoma of the vulva with signet ring cells deriving from the cloaca.

Vulvar neoplasias are rarely encountered lesions at female genital tract, regardless if they are primary or metastatic. Presence of signet ring cells in a tumour at female genito-urinary tract is highly suggestive of a metastatic lesion particularly from a gastrointestinal tumour. Here the authors present a case of vulvar carcinoma with signet ring cells with an undetermined primary site possibly originating from embryonic cloaca.

The efficacy and safety of capecitabine plus bevacizumab combination as first-line treatment in elderly metastatic colorectal cancer patients.

AIM: The optimal treatment in older persons with metastatic colorectal cancer (mCRC) is complicated by a lack of general agreement. The aim of this study was to evaluate the activity of bevacizumab plus capecitabine combination in elderly mCRC patients who were not suitable for chemotherapy with irinotecan and oxaliplatin-containing regimens. MATERIALS AND METHODS: Seventy years and older patients with metastatic colorectal carcinoma were included in this retrospective study. Bevacizumab was administered at a dose of 7.5 mg/kg on day 1 as an intravenous (IV) infusion over 30-90 min every 21 days, and capecitabine was prescribed at 1000 mg/m(2) twice daily on days 1-14 of the same 21-day schedule. RESULTS: Eighty-two consecutive patients (47 men, 35 women) were included in the study. The mean age was 75.5 (SD 3.9, range 70-87). Half of the patients were older than 75 years. There were 55 patients (67.1 %) with a good Eastern Cooperative Oncology Group (ECOG) performance status (PS: 0-1) and the remaining 27 patients (32.9 %) had a poor ECOG performance status (PS: 2). With a median follow-up period of 18.5 months, the median progression-free survival (PFS) was 10 months (95 % CI, 7.8-12.1) and the median OS was 25 months (95 % CI, 18.6-31.3). The main toxicities recorded were non-hematological. Thirty-one patients (37 %) experienced grade 3/4 adverse events, the most common being hand-foot syndrome (9.8 %). No fatal toxicity resulting from this regimen was recorded. CONCLUSIONS: Considering the toxicity profile and survival outcomes, the combination regimen of capecitabine and bevacizumab is a potentially feasible treatment option in elderly mCRC patients.

The role of reactive oxygen species in the antibacterial photodynamic treatment: photoinactivation vs proliferation.

UNLABELLED: Low-level light/low concentration of reactive oxygen species (ROS) may trigger some biochemical pathways that lead to cell proliferation. Thus, there is a risk of stimulation of bacterial cell proliferation during photodynamic therapy (PDT). In this study, PDT with different doses of 809-nm laser and indocyanine green (ICG) was investigated in vitro for safe bactericidal application. The combined effect of laser doses with ICG concentrations were examined on Pseudomonas aeruginosa in vitro. Data showed that low energy dose and ICG concentration caused bacterial cell proliferation. When these parameters were increased high enough, photoinactivation of the bacteria was achieved. Energy dose and photosensitizer concentration ranges at which proliferation, cell death or neither observed were determined. Furthermore, l-histidine was used as a scavenger of ROS to block the mechanism of biostimulation and cell killing. It inhibited proliferation when laser dose and ICG concentrations were low. It also inhibited cell killing when dose and concentration were high. Data showed that mechanisms of proliferation and cell killing depend on the amount of ROS and antibacterial photodynamic treatment have serious biostimulative risk. Effective range might need to be determined before any therapeutic usage. The risk seems to exist specifically at lower energy doses and photosensitizer concentrations. SIGNIFICANCE AND IMPACT OF THE STUDY: The main purpose in antibacterial photodynamic therapy (PDT) is to kill the micro-organisms that cannot be destroyed by conventional methods. Low-level light and/or low concentration of reactive oxygen species may trigger some biochemical pathways that lead to cell proliferation. Thus, there is a risk of bacterial cell proliferation during PDT. In this study we report that PDT with ICG application can induce biostimulation when laser dose and photosensitizer concentration are not optimized properly. Therefore, optimum dosimetry in PDT possesses great importance in the treatment of wounds infected by antibiotic-resistant bacteria.

Determinants of nocebo effect during oral drug provocation tests

BACKGROUND: A 'nocebo' effect is defined as troublesome symptoms after the administration of placebo. The aim of this study was to determine characteristics of nocebo responses and related factors. METHODS: Patients with a reliable history of drug-induced hypersensitivity reactions subjected to placebo-controlled oral drug provocation tests and reacted to placebo, were consecutively included in this case-control study. Controls consisted of the randomly selected subjects who had a history of drug hypersensitivity reaction but did not react to placebo. A structured questionnaire was performed by an allergy specialist. RESULTS: There were 137 subjects (mean age: 43.10 ± 12.65 years), with nocebo and 91 subjects (42.38 ± 12.18 years) without any reaction to placebo. Most nocebo reactions (71.5%, n = 98) were classified as subjective, with local pruritus as the most common finding. A minority of nocebo reactions (11.7%,n = 16) were objective as cutaneous reactions including flushing and urticaria. Factors related with nocebo risks were university graduation (OR: 2.96, 95% CI: 1.27-6.93, p = 0.012) and non-atopy (OR: 2.12, 95% CI: 1.02-4.40, p = 0.043). In terms of the time of first and last historical reaction to drugs, each 1-unit (a month) increase in first reaction time (OR: 1.008, 95% CI: 1.00-1.02, p = 0.001) and last reaction time (OR: 1.019, 95% CI: 1.01-1.03, p < 0.001) were associated with increased nocebo risk. CONCLUSION: In conclusion, subjects with high education, non-atopy, and older drug hypersensitivity reactions history seem to be more likely to experience nocebo effect during oral drug provocation tests. These risk factors should be considered and managed accordingly to complete the drug provocation procedure successfully

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Prognostic significance of ADAM17 expression in patients with gastric cancer who underwent curative gastrectomy

Backgrounds. A disintegrin and metalloproteinase (ADAM) 17 has been indicated to be an indispensable regulator of cellular events from proliferation to migration. Although prognostic importance of ADAM17 expression has been investigated in several tumours, its clinical utility as a useful prognostic molecular marker remains unclear in gastric cancer. In the current study, we evaluated the expression of ADAM17 and its prognostic significance in gastric cancer patients after curative gastrectomy. Methods. The prognostic significance of ADAM17 expression was analysed immunohistochemically in 156 patients with gastric cancer who had undergone curative gastrectomy, and the relationship between its expression and clinicopathological factors was also evaluated. Results. High ADAM17 expression was detected in 79 patients (51 %), whereas low expression was found in 77 cases (49 %). There was significant correlation between gender, histology, lymph node metastasis, vascular invasion, the presence of recurrence and high ADAM17 expression. Recurrence in patients with high ADAM17 expression was significantly higher than that for patients with low ADAM17 expression (p = 0.032). The median disease-free survival (DFS) time for patients with tumours with high ADAM17 expression was worse than that of patients with tumours with low ADAM17 expression (16.6 vs. 44.2 months, p = 0.004). In addition, patients with low ADAM17 expression had a higher median overall survival (OS) (49.6 vs. 26.9 months, p = 0.019) compared to those with high ADAM17 expression. Multivariate analysis indicated that the rate of ADAM17 expression was an independent prognostic factor for DFS, in addition to the already known important clinicopathological prognostic indicator. But the prognostic importance of ADAM17 expression could not be proved by multivariate analysis for OS. Conclusions. The potential value of ADAM17 expression as a useful molecular marker in gastric cancer progression should be evaluated comprehensively; it may predict recurrence and poor prognosis in patients with gastric cancer after curative resection (AU)

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Management of a Benign Phyllodes Tumor in a 13-Year-Old Girl with Trans-position of the Nipple Areola Complex and Breast Reconstruction.

Phyllodes tumor is a rare primary tumor of the breast. In children and adolescents, it is even rarer with only 20 cases, treatment of which vary in the literature. Herein we report the case of a 13-year-old female patient with a giant benign phyllodes tumor eroding the bottom of the breast skin and causing nipple retraction. We performed breast conservative surgery by mobilizing the areola, using skin flaps and inserting an implant. Breast malignancy, including phyllodes tumor (PT), is very rare in adolescents. PT, previously called cystosarcoma phylloides, consists of leaf-like fronds, from which the tumor gets its name (1, 2). Although PT is most often seen in the fourth decade of life, almost 20 cases have been reported in the adolescent period, most of which are benign. The histologic types are benign, borderline, and malignant, depending on the mitotic rate of the tumor (3, 4).

Evaluation of vascular endothelial growth factor-A and Endostatin levels in induced sputum and relationship to bronchial hyperreactivity in patients with persistent allergic rhinitis monosensitized to house dust.

BACKGROUND: Studies about the pathogenesis of bronchial hyperreactivity (BHR) in patients with persistent allergic rhinitis (PAR) and its relationship with lower airway remodeling are extremely limited. OBJECTIVE: This study evaluated bronchial vascular remodeling via the measurement of angiogenic factor, vascular endothelial growth factor-A (VEGF-A), and anti-angiogenic factor, Endostatin, and evaluated their relationship with BHR in patients with PAR. METHODS: The study group consisted of 30 patients with PAR monosensitized to house dust mites and 14 non-allergic healthy controls. All subjects underwent induced sputum and methacholine (M) bronchial provocation tests. VEGF-A and Endostatin levels were measured by ELISA in induced sputum supernatants. RESULTS: The percentages of eosinophils in induced sputum were significantly increased in patients with PAR compared with healthy controls. There were no significant differences between patients with PAR and healthy controls in terms of levels of VEGF (37.9pg/ml, min-max: 5-373pg/ml vs. 24.9, min-max: 8-67pg/ml, p=0.8 respectively), Endostatin (532.5pg/ml, min-max: 150-2125pg/ml vs. 644, min-max: 223-1123pg/ml, p=0.2 respectively) and VEGF/Endostatin ratio (0.057 vs. 0.045, p=0.8 respectively). In addition, there were no significant differences between patients who are BHR positive (n=8), or negative to M (n=22) in terms of levels of VEGF, Endostatin and VEGF/Endostatin ratio and no correlations among value of PD20 to M and levels of VEGF, Endostatin and VEGF/Endostatin ratio. CONCLUSION: We conclude that VEGF-A and Endostatin did not differ between patients with PAR and healthy controls regardless of BHR to M.