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Showing papers by "Alexandra Giatromanolaki published in 2011"


Journal ArticleDOI
TL;DR: Assessment of the CD44/CD24 status may reveal distinct subgroups of breast cancer patients with different clinical behavior, and the unsatisfactory response of the triple-negative tumors to current chemotherapy and their intimate link with theCD44(+)/CD24(−) phenotype, makes CD44 targeting an attractive therapeutic alternative for Breast cancer patients.
Abstract: Breast carcinomas have been reported to contain a subpopulation of CD44+/CD24− tumor cells with stem cell–like properties. This study investigates the significance of these two molecules in connection with tumor aggression and prognosis. The phenotypic profile of 139 breast carcinomas was investigated in paraffin sections using markers previously associated with stem cell–like properties (CD44, CD24), the “triple-state” (ER, PR, c-erb-B2), and angiogenesis (CD31). Tumors with >10% of CD44 and CD24 cancer cells were considered positive. The prevalence of CD44+ and CD24+ breast carcinomas in the series was 51.8% and 41.7%, respectively. Patients with the CD44(+)/CD24(−) phenotype had a 10-year lower median age at presentation and harbored tumors with a triple-negative state. They experienced an unfavorable prognosis. Lack of CD44 expression was associated with lymph node involvement, regardless of CD24 status, whereas the lack of both CD44 and CD24 was connected with high histologic grade and unfavorable prognosis which, notably, was the worse among all phenotypes. In multivariate analysis, the CD44(−)/CD24(−) phenotype, the nodal involvement, the vascular density and the ER-/PR-/c-erbB-2-profile were independent prognostic variables. It is concluded that assessment of the CD44/CD24 status may reveal distinct subgroups of breast cancer patients with different clinical behavior. The unsatisfactory response of the triple-negative tumors to current chemotherapy and their intimate link with the CD44(+)/CD24(−) phenotype, makes CD44 targeting an attractive therapeutic alternative for breast cancer patients. The strong association between the CD44(−)/CD24(−) phenotype and prognosis requires further investigation.

133 citations


Journal ArticleDOI
TL;DR: Serum LDH and tissue LDH5 levels are complementary features that help to characterize the activity of LDH in colorectal cancer and have a potent value in predicting response to chemotherapy.
Abstract: Purpose: The Colorectal Oral Novel therapy For the Inhibition of angiogenesis and Retarding of Metastases (CONFIRM)-randomized trials, investigating the role of the VEGF-receptor inhibitor PTK787/ZK 222584 (vatalanib) in colorectal cancer (FOLFOX 4 ± vatalanib), showed some benefit in patients with high serum lactate dehydrogenase (LDH) levels. Here, we investigated the expression of LDH5 (encoded entirely by the LDHA gene, regulated by the hypoxia inducible factors) in cancer tissues from patients recruited in the CONFIRM trials and relationship to response. Experimental Design: Paraffin-embedded materials from 179 patients recruited in the CONFIRM trials were analyzed by immunohistochemistry for the expression of the LDH5 protein. Correlations with serum LDH, response, and survival were assessed. Results: A significant association of tumor burden and of poor performance status (PS) with serum LDH was noted. Poor PS and high tumor LDH5 expression predicted for poor response rates. High tissue LDH5 was related to poor progression-free survival (PFS) only in the placebo group of patients, whereas the addition of vatalanib seemed to improved response and PFS in this subgroup. High serum LDH levels were linked with significantly poorer overall survival, which however was not sustained in multivariate analysis. Conclusions: Serum LDH and tissue LDH5 levels are complementary features that help to characterize the activity of LDH in colorectal cancer and have a potent value in predicting response to chemotherapy. The addition of vatalanib diminished the impact of LDH expression on the prognosis of patients. Clin Cancer Res; 17(14); 4892–900. ©2011 AACR .

123 citations


Journal ArticleDOI
01 Jul 2011-Chest
TL;DR: Exaggerated autophagic activity, as indicated by the intense presence of SLSs, is strongly correlated with a poor outcome in non-small cell lung carcinoma, suggesting possibly that autophagy functions as a survival tool in cancer cells.

80 citations


Journal ArticleDOI
TL;DR: Atg6/beclin 1 was proved to be capable of deciphering the prognosis in cutaneous malignant melanoma, whereas angiogenesis maintains low autophagic activity.
Abstract: Autophagy is an intracellular pathway for the degradation of long-lived proteins and damaged organelles. It is, in essence, a recycling process allowing cells to survive oxygen and nutrient depletion. The expression of two autophagy-related proteins, beclin 1 and light chain 3A (LC3A) was investigated in 79 nodular cutaneous melanomas. The results were correlated with histopathological factors, vascular density, and hypoxia-related proteins [hypoxia-inducible factors (HIF1α and HIF2α) and lactate dehydrogenase 5]. The reactivity of both autophagy-related proteins was uniformly cytoplasmically diffused. High beclin 1 and LC3A reactivity was related to tumor hypoxia, as this was inferred from the intense expression of HIF1α and lactate dehydrogenase 5, whereas low beclin 1 and LC3A expression was linked with an increased vascular density. In addition, beclin 1 was related to disease-specific survival which, however, exposed a biphasic pattern. A strong beclin 1 expression extending over a tumor area of more than 50% (high) was associated with an increased rate of early deaths, whereas a similarly strong, but less-extensive cytoplasmic reactivity (<10% tumor area; low) defined a sharp fall in the survival 5 years after surgery. Furthermore, the low beclin 1 expression was associated with high Breslow's depth, high Clark's level, and ulceration. Low LC3A expression was also related to ulceration, but not to other histopathological features nor prognosis. In multivariate analysis, beclin 1 was an independent prognostic variable. It is concluded that extensive autophagic activity is generated by tumor hypoxia and anaerobic glycolysis, whereas angiogenesis maintains low autophagic activity. Atg6/beclin 1 was proved to be capable of deciphering the prognosis in cutaneous malignant melanoma, but the matter requires further investigation.

78 citations


Journal ArticleDOI
TL;DR: An increased Beclin 1 expression is connected with the most aggressive endometrioid adenocarcinomas, probably as a result of its strong association with tumor hypoxia.

73 citations


Journal ArticleDOI
TL;DR: It is concluded that the endogenous LC3A processing is a major marker of autophagy flux in mouse model and should be used in immunobloting to allow discrimination between the LC3-I soluble and theLC3-II membrane protein and kinetics.
Abstract: Autophagy is a major intracellular pathway for the degradation and recycling of long-lived proteins, mature ribosomes and even entire organelles. The best studied autophagic marker is the LC3B and it is believed that only the amount of the LC3B-II correlates with the amount of the autophagic membranes. Whether the LC3A processing, aside to LC3B, is a valuable endogenous 'autophagic flux' marker is far less clear. The specificity of rabbit polyclonal antibodies to the LC3A and the LC3B was tested against the commercial available human recombinant proteins LC3A and LC3B. In order to measure 'autophagic flux' in mouse liver, lung, kidney and heart we used: (1) a lysosomotropic reagent chloroquine, which inhibit the intra-lysosomal acidification or their fusion with autophagosome, (2) nutrient starvation as an autophagic stimulus and (3) ionizing radiation, which is known to destabilize lysosomes. According to the immunoblotting work the LC3A protein follows discrete patterns of LC3A-I and LC3A-II changes in liver, lung, kidney and heart tissues of mice, whereas the LC3B protein didn't follow the same pattern under stressor conditions. We conclude that the endogenous LC3A processing is a major marker of autophagy flux in mouse model. Fractionated samples (soluble vs. membrane fractions) should be used in immunoblotting to allow discrimination between the LC3-I soluble and the LC3-II membrane protein and kinetics. Further, when dealing with in vivo models it is necessary to check the specificity of the antibodies used against the LC3A and LC3B proteins as their expression and responsiveness is not overlapping.

56 citations


Journal ArticleDOI
TL;DR: An assessment of autophagic activity, particularly in the form of SLS, is useful for evaluating tumor aggressiveness and, in the absence or an excess of S LS, it may also prove valid for differentiating grade 1 endometrioid adenocarcinomas from their precursor lesions.
Abstract: Autophagy, as an intracellular adaptation mechanism for oxygen and nutrient deprivation, is associated with tumor cell survival and aggressiveness. This was reaffirmed in a series of 360 endometrial carcinomas, using a standard immunohistochemical technique and the LC3A antibody, capable of recognizing both the soluble (LC3A-I) and the membrane-bound form (LC3A-II) of the protein. LC3A reactivity was recognized in three basic patterns-diffuse cytoplasmic, cytoplasmic/juxta-nuclear, and the so-called "stone-like" structures (SLS). The latter has emerged as the: hallmark of autophagic activity, being detected exclusively in endometrial carcinomas and their immediate precursor lesions, namely the atypical hyperplasias, albeit in small numbers. Other forms of hyperplasia without cytological atypia and normal endometrial tissues expressed only cytoplasmic staining patterns. High SLS counts, presumed to reflect excessive levels of autophagic activity, were associated with tumors of extremely poor prognosis. In contrast, a basal level of autophagic activity, as exemplified by the diffuse cytoplasmic and the cytoplasmic/juxta-nuclear patterns, had no impact on prognosis. Survival, according to tumor cell types, showed that serous papillary, clear cell and the high-grade endometrioid carcinomas had the worst prognosis compared to low-grade endometrioid carcinomas, but interestingly, within this tumor group, those having high-SLS counts had a much worse survival rate than those that did not. It is concluded that an assessment of autophagic activity, particularly in the form of SLS, is useful for evaluating tumor aggressiveness and, in the absence or an excess of SLS, it may also prove valid for differentiating grade 1 endometrioid adenocarcinomas from their precursor lesions.

55 citations


Journal ArticleDOI
TL;DR: It is concluded that autophagy is commonly upregulated in uveal melanomas, and may be associated with hypoxia and intense pigmentation, and there is a strong association between extensive BECN1 overexpression and early metastases/poor prognosis, and between underexpression of this protein and late metastases and better prognosis.

48 citations


Journal ArticleDOI
TL;DR: This brief account of endometrial carcinogenesis at menopause re-evaluates issues and proposes the separation of G1 endometrioid adenocarcinomas (low-grade tumours) from all others (high- grade tumours).
Abstract: Almost a third of the life of a woman is now postmenopausal, and during this period over 80% of endometrial carcinomas develop. This is by far the most common gynaecological malignancy in the industrialised world and, probably, the less completely understood with regard to its pathogenesis after the menopause. For while it is generally thought that these neoplasms are non-oestrogen-induced, we are, at the same time, informed that oestrogenic stimulation is continuous during menopause through increases to oestrone formation in the adipose tissue from androgens of adrenal and ovarian origin. Furthermore, the postmenopausal endometrium has been typified as atrophic, which is indeed true, but is also implied as being inactive, which in fact it is not; in most cases, the postmenopausal endometrium appears to be weakly proliferative with potential to give rise to an endometrial carcinoma. It is also assumed that postmenopausal endometrial tumours are predominantly of serous papillary and clear cell type, and, in general, they are not well-differentiated endometrioid carcinomas; in reality, no more than 15% are serous papillary and clear cell carcinomas, and no less than 55% are well-differentiated endometrioid neoplasms. The overall prognosis is presumed to be poor, yet postmenopausal patients harbouring well-differentiated endometrioid carcinomas have the same excellent prognosis as those premenopausal women having endometrioid tumours of similar grade and stage. This brief account of endometrial carcinogenesis at menopause re-evaluates these issues and, in the light of new and old evidence, proposes the separation of G1 endometrioid adenocarcinomas (low-grade tumours) from all others (high-grade tumours).

35 citations


Journal ArticleDOI
TL;DR: Autophagic activity in SCC, when expressed as high LC3A/SLS counts, can be regarded as an indicator of tumor aggressiveness, and MIB1 proliferation index increased with tumor thickness and was directly linked with SLS counts and inversely with the cytoplasmic pattern.
Abstract: This study was set to investigate the relation between autophagic activity and the aggressiveness of cutaneous squamous cell carcinomas (SCC), as indicated by tumor thickness and proliferative activity. The anti-LC3A antibody, recognizing both the soluble and the autophagosome-bound forms of the protein, and a standard immunohistochemical technique were applied to 75 cutaneous SCC of variable tumor thickness. The study was complemented by staining for MIB1. Three patterns of LC3A reactivity were recognized: diffuse cytoplasmic, cytoplasmic/perinuclear, and "stone-like" structures (SLS), that is, large, rounded, densely stained amorphous material, 5 μm on average, enclosed within cytoplasmic vacuoles. Higher numbers of SLS were counted in >6-mm-thick SCC compared with the intermediate-thickness tumors (2.1-6 mm) and the <2-mm-thick tumors; the mean recorded values, being 8.8, 4.55, and 1.55, respectively, were statistically significant. The diffuse cytoplasmic staining showed a nearly inverse trend, whereas the perinuclear pattern, expressed in <10% of the total, was not evaluated. With regard to MIB1 proliferation index, this increased with tumor thickness and, in linear regression analysis, was directly linked with SLS counts and inversely with the cytoplasmic pattern. These data suggest that autophagic activity in SCC, when expressed as high LC3A/SLS counts, can be regarded as an indicator of tumor aggressiveness.

33 citations


Journal ArticleDOI
TL;DR: Bvacizumab can be safely combined with hypofractionated radiotherapy and capecitabine as a preoperative radiochemotherapy regimen for patients with rectal cancer and the high pathologic complete response rates urges the testing of bevacIZumab in randomized studies.
Abstract: Purpose Bevacizumab has established therapeutic activity in patients with metastatic colorectal cancer, and anti–vascular endothelial growth factor therapy enhances the activity of radiotherapy in experimental models. We assessed the feasibility and efficacy of preoperative radiochemotherapy combined with bevacizumab in patients with rectal cancer. Methods and Materials Nineteen patients with radiologic T3 and/or N+ rectal carcinoma were treated with preoperative conformal hypofractionated accelerated radiotherapy (3.4 Gy in 10 consecutive fractions) supported with amifostine (500–1,000 mg daily), capecitabine (600 mg/m 2 twice daily, 5 days per week), and bevacizumab (5 mg/kg every 2 weeks for 2 cycles). Surgery followed 6 weeks after the end of radiotherapy. A cohort of 14 sequential patients treated with the same regimen without bevacizumab was available for comparison. Results Grade 2 or 3 diarrhea was noted in 7 of 19 patients (36.8%), which was statistically worse than patients receiving the same regimen without bevacizumab ( p = 0.01). A higher incidence of Grade 2 or 3 proctalgia was also noted (21.1%) ( p = 0.03). Bladder and skin toxicity was negligible. All toxicities regressed completely within 2 weeks after the end of therapy. Pathologic complete and partial response was noted in 7 of 19 cases (36.8%) and 8 of 19 cases (42.1%). Within a median follow-up of 21 months, none of the patients has had late complications develop and only 1 of 18 evaluable cases (5.5%) has had locoregional relapse. Conclusions Bevacizumab can be safely combined with hypofractionated radiotherapy and capecitabine as a preoperative radiochemotherapy regimen for patients with rectal cancer. The high pathologic complete response rates urges the testing of bevacizumab in randomized studies.

Journal ArticleDOI
01 Mar 2011-Cytokine
TL;DR: Serum VEGF levels are increased in patients with breast and gynecological malignancies, but this can not be considered pathognomonic for cancer as it is also increased in certain benign conditions, including cases of fibroadenoma, fibrocystic disease of breast and simple endometrial hyperplasia.

Journal ArticleDOI
TL;DR: In this region, the percentage of preschool-aged Muslim children with acute appendicitis was remarkably high and one possible explanation for this finding could be the higher amount of lymphoid tissue in the wall of the appendix in Muslim preschool children together with their low standard of hygiene.
Abstract: Objective To assess the incidence and the risk factors implicated in acute appendicitis in preschoolers in our region.

Journal ArticleDOI
TL;DR: It is suggested that irradiation induces dysfunction of the autophagic machinery in normal lung, characterized by decreased transcription of theLC3A/Beclin-1 mRNA and accumulation of the LC3A, and p62 proteins.

Journal ArticleDOI
TL;DR: Given their high tissue concentrations after RTA application, fibronectin, collagen III, CD68, and MMP-9 deserve further study as candidate modulators of the INT wound-healing process.
Abstract: BACKGROUND Data on the molecular processes involved in nasal mucosa wound healing after radiofrequency tissue ablation (RTA) of the inferior nasal turbinate (INT) are missing. This study was designed to examine tissue expression of fibronectin, collagen III, CD68, and matrix metalloproteinase (MMP) 9 in the INT (ventral) after RTA in sheep. METHODS An experimental randomized controlled study was performed. Seventeen INTs (ventral) of nine sheep were used. RTA was applied in 12 INTs. Turbinate samples were studied 1, 3, and 8 weeks postoperatively (4 samples/time point) and in five control INTs (without surgery). Besides hematoxylin and eosin staining, immunostaining was done for MMP-9, collagen III, fibronectin, and CD68. A quantitative grading ranging between 0 (no immunoreactivity at all) and 100% (profuse immunoreactivity) was performed by a blinded senior pathologist. Comparisons between groups were performed using Mann-Whitney U test and Kruskal-Wallis one-way ANOVA. Spearman's rho correlation coefficients were calculated between histological and/or immunohistological variables. RESULTS At week 8, fibronectin (p = 0.025), collagen III (p = 0.004), and MMP-9 (p < 0.001) immunoreactivity was significantly higher than controls, while immunoreactivity for CD68 was higher, although not significantly (p = 0.114) compared with controls. Strong correlations have been found between mucosal vascularization and interstitial space volume (r = 0.776), interstitial space volume and epithelial cell necrosis (r = 0.730), and CD68 immunostaining and epithelial cell necrosis (r = 0.784). CONCLUSION Given their high tissue concentrations after RTA application, fibronectin, collagen III, CD68, and MMP-9 deserve further study as candidate modulators of the INT wound-healing process.

Journal Article
01 Mar 2011-in Vivo
TL;DR: It is suggested that randomized trials should be re-appraised adopting amifostine schedules close to the maximum tolerable dose and that a slight reduction of the daily am ifostine dose can substantially reduce the clinical protective effect during fractionated radiotherapy.
Abstract: Background: Amifostine is an important broad spectrum cytoprotective agent approved for protection during fractionated radiotherapy. The daily dose of amifostine used, however, is arbitrarily chosen and low compared to the actual tolerable dose. Materials and Methods: Cohorts of mice (n=6) were treated with one up to 4 consecutive fractions of 6 Gy of whole-body γ-irradiation ( 60 Co), supported with increasing daily subcutaneous (s.c.) doses of amifostine (10 mg/g-300 mg/g). Survival and weight loss were monitored. Histopathological analysis was performed in mice receiving 3×6 Gy. Results: By increasing the amifostine dose from 13 to 50 mg and to 160 mg/g, the 50% lethal dose of radiotherapy increased from 2×6 Gy to 3×6 Gy and to 4×6 Gy, respectively. To keep the median weight loss to less than 25% of the initial weight, the dose of amifostine demanded was 23 mg/g, 68 mg/g and 121 mg/g, for 2×6 Gy, 3×6 Gy and 4×6 Gy, respectively. Histopathological analysis revealed a net protection of the liver and intestine of the mice receiving amifostine. Extensive and multiple vacuolar degeneration of the cytoplasm with focal necrosis of hepatocytes and loss of the intestinal villi was the most striking finding in the dying mice treated without amifostine. Conclusion: Taking into account the strong association of daily amifostine dose with cytoprotective efficacy and that a slight reduction of the daily amifostine dose can substantially reduce the clinical protective effect during fractionated radiotherapy, it is suggested that randomized trials should be re-appraised adopting amifostine schedules close to the maximum tolerable dose. Amifostine is an important broad-spectrum cytoprotective agent approved for the prevention of cisplatin-related toxicities

Journal Article
TL;DR: HypoARC is feasible and safe for patients with low-risk prostate cancer and, considering also the high efficacy noted, a strong rationale is provided for the further evaluation of HypoARC in randomized trials.
Abstract: Aim: Radiobiological analysis of clinical data suggests that prostate cancer has a low α/β ratio, implying that large radiotherapy fractions may better control the disease. Acceleration of radiotherapy may be also of importance in a subset of tumors. In this study we assessed the feasibility and efficacy of a highly accelerated and hypofractionated scheme of radiotherapy (Hypo ARC), for the treatment of localized low risk prostate cancer. Patients and Methods: Fifty-five patients with prostate cancer (T1-2 stage, Gleason score <7 and prostate specific antigen (PSA) <10 ng/ml) were treated with localized conformal 4-field radiotherapy to the prostate and seminal vesicles: 51 Gy were delivered (3.4 Gy/fraction, within 19 days). The biological dose to the prostate ranged from 67.9-91.7 Gy. Amifostine (0-1000 mg depending upon tolerance) was delivered daily for cytoprotection. The median follow-up of patients is 30 (6-69) months. Results: Early toxicity was overall low, proctitis being the most frequent side-effect (23.6% grade II). High dose amifostine significantly protected against proctitis (p=0.005). Grade 2 frequency and dysurea occurred in 1.8% and 3.7% of cases, respectively. There was no late toxicity ≥grade 2. Amifostine significantly protected against chronic frequency (p=0.02). Within a median follow-up of 30 months, one patient (1.8%) experienced a biochemical relapse. Conclusion: HypoARC is feasible and safe for patients with low-risk prostate cancer and, considering also the high efficacy noted, a strong rationale is provided for the further evaluation of HypoARC in randomized trials.

Journal ArticleDOI
TL;DR: The findings support the diagnostic and potential prognostic value of these markers in the clinical assessment of breast cancer.
Abstract: Expression of estrogen (ER) and progesterone receptors, c-erbB-2 oncogene, mutant p53 antioncogene (mp53), e-cadherin adhesion, and apoptotic caspase-8 antigens in tumor relative to matched normal tissue specimens from 102 unselected patients with primary ductal breast carcinoma of various tumor grades was assessed by immunohistochemistry and correlated with patient's biologic and clinical features, such as age, menstrual status, age of menarche, tumor grade and diameter, the presence or absence of metastases, and number of infiltrated lymph nodes. We observed association of e-cadherin adhesion, ER and progesterone antigen marker expression with low histologic grade tumors and limited number of lymph node metastases and of c-erbB-2, mp53, and casp-8 antigen marker expression with high histologic grade tumors and increased number of lymph node metastases. We also observed strong correlation (P<0.05) between 4 of the 6 biomarkers and 4 of the 7 patient/tumor parameters examined. Our findings support the hypothesis of independent expression of these 4 strong biomarkers and reveal that nearly 40% of all breast tumor cases studied express similar proportions of 2 major phenotypic combinations [ER/c-erbB-2/mp53/casp-8: +/+/-/+ (19.6%) & +/-/-/+ (17.8%)]. We conclude that, in agreement with earlier reports, our findings support the diagnostic and potential prognostic value of these markers in the clinical assessment of breast cancer.

Journal ArticleDOI
TL;DR: The experience in such a case treated with transurethral resection followed by radiotherapy with adverse final outcome is reported, indicating Radiotherapy alone is insufficient as a treatment option of these aggressive tumors.
Abstract: Carcinosarcoma of the bladder is an unusual tumour characterized by a combination of malignant epithelial and soft tissue elements Most of the reported cases have been case reports or small series Optimal treatment is uncertain We herein report our experience in such a case treated with transurethral resection followed by radiotherapy with adverse final outcome Treatment of bladder carcinosarcomas should be aggressive and multimodal but optional treatment is still unknown Radiotherapy alone is insufficient as a treatment option of these aggressive tumors

Journal ArticleDOI
TL;DR: Sharp rise of CRP levels on the day after the fever/rash development suggest amifostine-related etiology of fever/ rash, and abnormal initialCRP levels and/or high CRP Levels on day 7 should be considered as an alert signal as the probability to develop fever/Rash reaches the 30%.
Abstract: INTRODUCTION Fever/rash is a side-effect of amifostine that demands immediate interruption of the drug. Here, we focus on the role of C-reactive protein (CRP) as a putative marker linked with amifostine fever/rash. MATERIALS AND METHODS The CRP serum values were analyzed in 496 patients receiving radiotherapy supported with amifostine (500-1000 mg/d). CRP levels were recorded before the onset of radiotherapy (day 0), on day 15 and when the fever/rash appeared. For 121 out of 496 patients, CRP values on day 7 were also available. About 79 patients (15.9%) developed fever/rash symptoms. RESULTS The CRP levels before the onset of therapy were 0 to 20.7 mg/dL (normal, ≤0.5 mg/dL). For patients who did not develop fever/rash, the CRP levels increased from a median of 0.30 to 0.50 on day 15; P = 0.001. Patients who developed fever/rash showed a more than 7-fold increase of the median CRP levels (median, 3.50; P < 0.0001). This sharp CRP rise was specific for amifostine-related fever/rash. Initially abnormal CRP levels were linked with a 2-fold risk for fever/rash (P = 0.01), while abnormal levels on day 7 were linked with a 3-fold higher risk (P = 0.08). The occurrence of fever/rash was independent of the amifostine dose level. CONCLUSIONS Sharp rise of CRP levels on the day after the fever/rash development suggest amifostine-related etiology of fever/rash. Abnormal initial CRP levels and/or high CRP levels on day 7 should be considered as an alert signal as the probability to develop fever/rash reaches the 30%.

Journal ArticleDOI
TL;DR: Bile reflux gastropathy is associated with GERD severity, but not with oncogene expression or apoptotic discrepancies of the upper GI mucosa.
Abstract: Introduction The pathogenesis of GERD is strongly related with mixed acid and bile reflux Benign and malignant esophageal and gastric lesions have been associated with synergetic activity between those parameters Bile reflux causes reactive gastropathy evaluated with Bile Reflux Index (BRI) The aim was to investigate if the sequence: bile reflux-intestinal metaplasia-GERD-esophagitis, is associated with apoptotic/oncogenetic disturbances Materials/Methods Fifteen asymptomatic subjects and 53 GERD patients underwent gastroscopy with biopsies The specimens examined histologically and immunohistochemically for p53, Ki-67, Bax, and Bcl-2 Results Elevated BRI score detected in 47% (25/53) of patients with GERD and in 13% (2/15) of controls ( ) Severe esophageal lesions were significantly more common in BRI (+) patients (14/25) compared to BRI (−) ones ( ) Immunohistochemical analysis did not show associations between BRI score and biomarker expression Conclusions Bile reflux gastropathy is associated with GERD severity, but not with oncogene expression or apoptotic discrepancies of the upper GI mucosa

Journal ArticleDOI
TL;DR: Although its efficacy in terms of bladder tumour control rates could not be substantiated due to the high efficacy of the HypoARC regimen applied, survival was improved suggesting either a spatial co-operation or a radio-sensitization of pelvic in-field subclinical disease.
Abstract: Cisplatin-based radio-chemotherapy is an effective alternative to cystectomy. The position of cisplatin has been challenged by novel drugs, while altered radiotherapy fractionation is also tested against conventional radiotherapy (RT). This study focuses on liposomal doxorubicin (LDox) in combination with an aggressive radiotherapy scheme (HypoARC). Eighty-two bladder cancer patients were treated with hypofractionated/accelerated RT (14 × 2.7 Gy to the pelvis and 15 × 3.4 Gy to the bladder, within 19 days), supported with amifostine (0–1,000 mg sc.). Forty-one out of 82 patients received concurrently LDox (20 mg/m2 for 3 bi-weekly cycles). LDox was free of haematological toxicity, erythordysestesia grade 1 being the only side effect noted in 5/41 patients. Although the incidence of early toxicities did not increase with LDox, delays of radiotherapy were increased (P = 0.16). Amifostine significantly protected patients against toxicities and delays. There were no severe late complications recorded. Complete response rate was similar in both groups (85.4 vs. 87.8%). The 3-year local relapse-free survival was better in patients receiving LDox, but at a non-statistical level (64 vs. 47%; P = 0.59). The 3-year survival rate was significantly improved in T2-4 stage patients receiving LDox (72.1 vs. 58.7%; P = 0.04). Multivariate analysis did not identify any independent prognostic variables of relapse or death events. LDox is a well-tolerated drug during pelvic radiotherapy. Although its efficacy in terms of bladder tumour control rates could not be substantiated due to the high efficacy of the HypoARC regimen applied, survival was improved suggesting either a spatial co-operation or a radio-sensitization of pelvic in-field subclinical disease.

Journal ArticleDOI
TL;DR: A case of omental infarction in an obese 10-year-old boy who presented with acute abdominal pain in the right lower abdomen and was operated on under the preoperative diagnosis of acute appendicitis but the intra-operative finding was o mental infarct.
Abstract: Primary omental infarction (POI) has a low incidence worldwide, with most cases occurring in adults. This condition is rarely considered in the differential diagnosis of acute abdominal pain in childhood. Herein, we present a case of omental infarction in an obese 10-year-old boy who presented with acute abdominal pain in the right lower abdomen. The ultrasound (US) examination did not reveal the appendix but showed secondary signs suggesting acute appendicitis. The child was thus operated on under the preoperative diagnosis of acute appendicitis but the intraoperative finding was omental infarct. Since the omental infarct as etiology of acute abdominal pain is uncommon, we highlight some of the possible etiologies and emphasize the importance of accurate diagnosis and appropriate treatment of omental infarction.