Prognostic impact of margin status in liver resections for colorectal metastases after bevacizumab.

BACKGROUND: Margin status with resection of colorectal liver metastasis (CRLM) was an important prognostic factor in the years before the introduction of biological chemotherapy. This study examined outcomes following CRLM resection in patients who received neoadjuvant chemotherapy with or without the monoclonal antiangiogenic antibody bevacizumab. METHODS: Patients who underwent surgery for CRLM at the Johns Hopkins Hospital between 2000 and 2015 were identified from an institutional database. Data regarding surgical margin status, preoperative bevacizumab administration and overall survival (OS) were assessed using multivariable analyses. RESULTS: Of 630 patients who underwent CRLM resection, 417 (66·2 per cent) received neoadjuvant chemotherapy with (214, 34·0 per cent) or without (203, 32·2 per cent) bevacizumab. The remaining 213 (33·8 per cent) did not receive neoadjuvant chemotherapy. Univariable analysis found that positive margins were associated with worse 5-year OS than R0 resection (36·2 versus 54·9 per cent; P = 0·005). After dichotomizing by the receipt of preoperative bevacizumab versus chemotherapy alone, the prognostic value of pathological margin persisted among patients who did not receive preoperative bevacizumab (5-year OS 53·0 versus 37 per cent after R0 versus R1 resection; P = 0·010). OS was not significantly associated with margin status in bevacizumab-treated patients (5-year OS 46·8 versus 33 per cent after R0 versus R1 resection; P = 0·081), in whom 5-year survival was slightly worse (presumably reflecting more advanced disease) than among patients treated with cytotoxic agents alone. Pathological margin status was not significantly associated with 5-year OS in patients with a complete or near-complete response to chemotherapy and bevacizumab (43 versus 30 per cent after R0 versus R1 resection; P = 0·917), but this may be due to a type II error. CONCLUSION: The impact of margin status varied according to the receipt of bevacizumab. Bevacizumab may have a role to play in improving outcomes among patients with more advanced disease.

Socioeconomic disparities in survival from childhood leukemia in the United States and globally: a meta-analysis.

BACKGROUND: Despite advancements in the treatment of childhood leukemia, socioeconomic status (SES) may potentially affect disease prognosis. This study aims to evaluate whether SES is associated with survival from childhood leukemia. METHODS: The US National Cancer Institute Surveillance, Epidemiology and End Results Program (SEER) 1973-2010 data were analyzed; thereafter, results were meta-analyzed along with those from survival (cohort) studies examining the association between SES indices and survival from childhood leukemia (end-of-search date: 31 March 2014). Random-effects models were used to calculate pooled effect estimates (relative risks, RRs); meta-regression was also used. RESULTS: We included 29 studies yielding 28 804 acute lymphoblastic leukemia (ALL), 3208 acute myeloblastic leukemia (AML) and 27 650 'any' leukemia (denoting joint reporting of all subtypes) cases. According to individual-level composite SES indices, children from low SES suffered from nearly twofold higher death rates from ALL (pooled RR: 1.83, 95% confidence interval 1.00-3.34, based on four study arms); likewise, death RRs derived from an array of lower area-level SES indices ranged between 1.17 and 1.33 (based on 11 study arms). Importantly, the survival gap between higher and lower SES seemed wider in the United States, with considerably (by 20%-82%) increased RRs for death from ALL in lower SES. Regarding AML, poorer survival was evident only when area-level SES indices were used. Lastly, remoteness indices were not associated with survival from childhood leukemia. CONCLUSION: Children with lower SES suffering childhood leukemia do not seem to equally enjoy the impressive recent survival gains. Special health policy strategies and increased awareness of health providers might minimize the effects of socioeconomic disparities.

VEGF and Id-1 in pancreatic adenocarcinoma: prognostic significance and impact on angiogenesis.

OBJECTIVES: The significance of vascular endothelial growth factor (VEGF) and inhibitor of differentiation/DNA synthesis (Id-1) in tumor neoangiogenesis and tumor progression in pancreatic ductal adenocarcinoma (PDAC) is still unclear. Given the central role of VEGF in cancer angiogenesis and the inconclusive results on Id-1 expression in PDAC, it is of great interest to investigate whether Id-1 and VEGF expression are associated with angiogenesis and prognosis in PDAC. METHODS: Paraffin-embedded specimens from 60 consecutive patients with PDAC were immunostained for VEGF, Id-1 and CD34 and staining quantification was assessed by Image analysis system. The correlations among the expression of individual angiogenic factors and microvessel density (MVD), clinicopathologic features and clinical prognosis were analyzed. RESULTS: Id-1 and VEGF Positive Activity Indices (PAIs) closely correlated with each other. MVD positively correlated with both Id-1 and VEGF expression. More advanced T and N status correlated with more intense expression of Id-1, VEGF and higher MVD. With regard to prognostic significance higher Id-1 PAI (adjusted HR = 1.69, 95%CI: 1.10-2.59, p = 0.017), higher VEGF PAI (adjusted HR = 2.66, 95%CI: 1.09-6.50, p = 0.032), and MVD (adjusted HR = 1.55, 95%CI: 1.27-1.88, p < 0.001) were associated with poorer survival. CONCLUSIONS: VEGF and Id-1 overexpression were found to be associated with high MVD and emerged as adverse prognostic factors in terms of patient survival in PDAC. The potential of selective anti-angiogenic targeting therapy for pancreatic malignancies should prompt further validation of the present findings in studies encompassing larger samples and more elaborate techniques.

Aromatase inhibitors with or without gonadotropin-releasing hormone analogue in metastatic male breast cancer: a case series.

BACKGROUND: Data regarding the safety and effectiveness of aromatase inhibitors (AIs) as monotherapy or combined with gonadotropin-releasing hormone (GnRH) analogue in male breast cancer are scarce. METHODS: In this retrospective chart review, cases of male breast cancer patients treated with AIs with or without a GnRH analogue were evaluated. RESULTS: Twenty-three men were included into this case series. Aromatase inhibitors in combination with or without a GnRH analogue were given as first-line therapy in 60.9% and as second-line therapy in 39.1% of patients, respectively. All patients had visceral metastases, whereas in five of them bone lesions coexisted. In all cases AIs were tolerated well, and no case of grade 3 and 4 adverse events was reported. A partial response was observed in 26.1% of patients and stable disease in 56.5%. Median overall survival (OS) was 39 months and median progression-free survival (PFS) was 13 months. Regarding OS and PFS, no significant effects of GnRH analogue co-administration or type of AI were noted. CONCLUSION: Our study shows that AIs with or without GnRH analogues may represent an effective and safe treatment option for hormone-receptor positive, pretreated, metastatic, male breast cancer patients.

A cost-utility analysis of laparoscopic vs open treatment of colorectal cancer in a public hospital of the Greek National Health System.

PURPOSE: Laparoscopic colectomy has been reported as a safe and oncologically similar operation to open colectomy. A number of expensive surgical instruments are necessary for the procedure which should be applied if it is cost-effective for the patient and the health system in general. The purpose of the current study was the economic evaluation of laparoscopic compared to open colectomy for the treatment of colon cancer in the Greek national health system. METHODS: Fifty patients undergoing open colectomy and 42 undergoing laparoscopic colectomy were enrolled in this case-control study. Length of hospital stay, duration of operation, complication rates, cost of equipment used, total costs and three questionnaires measuring quality of life /QoL (EQ-5D, SF-36 and QLQ-C30) at baseline, 1 and 3 months after the operation were recorded. RESULTS: No statistically significant difference in QoL measured by QALYs between laparoscopic and open colectomy was observed. On the other hand, cost utility analysis revealed that laparoscopic colectomy was more expensive considering the advantages it offers. CONCLUSIONS: Laparoscopic colectomy is not superior to open colectomy on a QoL basis in the Greek public hospital system and is less cost-effective compared to the open procedure. Since the expensive equipment used in laparoscopic colectomy seems to be the causative factor for the high cost of this type of operation, an effort should be made to reduce it either by using reusable instruments or by implementing policies aiming at suppliers cutting down equipment charges.

An internet survey on self-reported food allergy in Greece: clinical aspects and lack of appropriate medical consultation.

BACKGROUND: Food allergy (FA) represents a common and worldwide disorder but in publications referring to FA the reported diagnosis is rarely confirmed. Consequently, the subjectively assessed FA may negatively affect the quality of life of patients and their families. OBJECTIVE: We have conducted this internet survey in order to estimate the self-reported perception of FA in Greece. METHODS: A standard anonymous questionnaire was posted for a 3-month period on http://www.in.gr, a Greek popular Internet portal. Each individual could participate only once. Participants were screened for the presence or history of FA by a key question and were then asked to provide information on symptoms, course and management. RESULTS: A total of 3673 adult subjects (mean age 34.2 years, range 18-74, females 61.3%), reporting FA were included in analysis. Most reported reactions were related to fruits (14.9%), seafood (10.7%) and nuts (9.2%). The first episode occurred principally during the second (29.2%) and third (30.9%) decade within 3 h from consumption (82.2%). Predominant symptoms were urticaria and oral allergy syndrome (almost 25% each one). Nearly half of the participants sought no medical advice, while 31.4% asked for an allergist's consultation. Almost 21% of reactors were hospitalized; nuts, severity of symptoms (lower respiratory and/or cardiovascular), onset in lower age, previous exercise and concomitant alcohol and/or aspirin intake were positively associated with hospitalization. CONCLUSION: Although FA causes severe anaphylactic episodes, almost 50% of individuals who experience symptoms perceived as FA do not seek medical advice. Awareness programmes must be carried out in order to increase consciousness about this potentially fatal medical condition.

Does hormone therapy, tibolone or raloxifene modify VEGF expression in cervical epithelial cells?

AIM: Vascular endothelial growth factor (VEGF) seems to be a critical molecule in cervical carcinogenesis. We aimed to investigate the possible associations between hormonal factors and VEGF expression in cervical epithelial cells from postmenopausal women. METHOD: A total of 105 healthy postmenopausal women (aged 45-68 years old) attending a university menopause clinic were enrolled in this cross-sectional study. Pap smears were derived from current users of 17ß-estradiol 1 mg + norethisterone acetate 0.5 mg (n = 28), tibolone 2.5 mg (n = 23), raloxifene HCl 60 mg (n = 21) and women not receiving treatment (n = 33). VEGF immunostaining was evaluated in squamous, glandular and metaplastic cells, using a semiquantitative method (rating scale: 0-3). RESULTS: Concerning endogenous hormones, higher Δ4-androstenedione levels were associated with more intense VEGF immunostaining in glandular (p = 0.041) and metaplastic cells (p = 0.004). Hormone therapy and raloxifene did not induce any changes in VEGF immunoreactivity in the examined cells. In contrast, tibolone administration was accompanied by diminished VEGF presence in metaplastic cells (p = 0.016 vs. controls). CONCLUSION: Our findings may in part reflect the molecular processes contributing to the safe profile of hormone therapy, tibolone and raloxifene in cervical carcinogenesis.

Is birth weight associated with childhood lymphoma? A meta-analysis.

Several risk factors have been identified for childhood lymphomas. The purpose of this meta-analysis was to synthesize current evidence regarding the association between birth weight with primarily the risk for non-Hodgkin lymphoma (NHL), given its similarity to acute lymphoblastic leukemia, Hodgkin lymphoma (HL) and any category of lymphoma. Two cohort (278,751 children) and seven case-control studies (2,660 cases and 69,274 controls) were included. Effects estimates regarding NHL, HL and any lymphoma were appropriately pooled using fixed or random effects model in two separate analyses: specifically, high was compared to normal or any birth weight. Similarly, low was compared to normal or any birth weight. No statistically significant association was found between high birth weight, as compared to normal birth weight, and risk for NHL plus Burkitt lymphoma (OR = 1.17, 95% CI = 0.76-1.80, random effects), HL (OR = 0.94, 95% CI = 0.64-1.38, fixed effects) or any plus Burkitt lymphoma (OR = 1.09, 95% CI = 0.76-1.56, fixed effects). A null association emerged when low was compared with normal birth weight for NHL plus Burkitt lymphoma (OR = 1.07, 95% CI = 0.71-1.62, random effects), HL (OR = 0.94, 95% CI = 0.54-1.65, fixed effects) or any plus Burkitt lymphoma (OR = 1.02, 95% CI = 0.79-1.33, fixed effects). Accordingly, no association was found when high or low birth weight was compared to any birth weight. Although current evidence suggests no association, birth weight might be a too crude indicator to reveal a genuine association of fetal growth with specific lymphoma categories; hence, there is an emerging need for use of more elaborate proxies, at least those accounting for gestational week.

Eversion versus conventional carotid endarterectomy: a meta-analysis of randomised and non-randomised studies.

BACKGROUND: To compare eversion (ECEA) and conventional (CCEA) carotid endarterectomy from randomised and non-randomised studies. METHODS: Pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) and numbers needed to treat (NNTs) were appropriately calculated. A sub-analysis was performed on studies directly comparing ECEA vs. patch CEA (PCEA). Meta-regression analysis was performed to examine the effect of potentially meaningful patient-related, procedure-related and definition-related modifiers. Power calculations were also conducted. RESULTS: A total of 21 studies were deemed eligible (8530 ECEA and 7721 CCEA procedures), seven of which were randomised and 14 non-randomised. ECEA was associated with significant reduction in perioperative stroke (OR = 0.46, 95%CI: 0.35-0.62, NNT = 68, 95%CI: 56-96), death (OR = 0.49, 95%CI: 0.34-0.69, NNT = 100, 95%CI: 85-185) and stroke-related death (OR = 0.40, 95%CI: 0.23-0.67, NNT = 147, 95%CI: 115-270); the results were replicated at the sub-analysis on PCEA. Concerning long-term outcomes, ECEA presented with a significant reduction in late carotid artery occlusion (OR = 0.48, 95%CI: 0.25-0.90, NNT = 143, 95%CI: 100-769) and late mortality (OR = 0.76, 95%CI: 0.61-0.94, NNT = 40, 95%CI: 25-167); the sub-analysis on PCEA replicated only the finding on late mortality. Meta-regression analysis did not point to significant effects mediated by the examined modifiers. Power calculations suggested adequate statistical power. CONCLUSIONS: ECEA compared to CCEA may be associated with a lower incidence in both short-term and long-term outcomes, which does not seem to be hampered by potentially meaningful modifiers.

Maternal smoking during pregnancy and childhood lymphoma: a meta-analysis.

Results from epidemiological studies exploring the association between childhood lymphoma and maternal smoking during pregnancy have been contradictory. This meta-analysis included all published cohort (n = 2) and case-control (n = 10) articles; among the latter, the data of the Greek Nationwide Registry for Childhood Hematological Malignancies study were updated to include all recently available cases (-2008). Odds ratios (ORs), relative risks and hazard ratios were appropriately pooled in three separate analyses concerning non-Hodgkin lymphoma (NHL, n = 1,072 cases), Hodgkin lymphoma (HL, n = 538 cases) and any lymphoma (n = 1,591 cases), according to data availability in the included studies. An additional metaregression analysis was conducted to explore dose-response relationships. A statistically significant association between maternal smoking (any vs. no) during pregnancy and risk for childhood NHL was observed (OR = 1.22, 95% confidence interval, CI: 1.03-1.45, fixed effects model), whereas the risk for childhood HL was not statistically significant (OR = 0.90, 95% CI: 0.66-1.21, fixed effects model). The analysis on any lymphoma did not reach statistical significance (OR = 1.10, 95% CI = 0.96-1.27, fixed effects model), possibly because of the case-mix of NHL to HL. No dose-response association was revealed in the metaregression analysis. In conclusion, this meta-analysis points to a modest increase in the risk for childhood NHL, but not HL, among children born by mothers smoking during pregnancy. Further investigation of dose-response phenomena in the NHL association, however, warrants accumulation of additional data.

Deregulation of EGFR/VEGF/HIF-1a signaling pathway in colon adenocarcinoma based on tissue microarrays analysis.

PURPOSE: Overexpression of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) in colon adenocarcinoma (CA) is a frequent event, whereas specific deregulation mechanisms in the corresponding signaling pathways remain under investigation. Our aim was to co-evaluate their expression correlated to the hypoxia inducible factor 1alpha (HIF-1a), which activates the transcription of VEGF gene. METHODS: 60 paraffin-embedded primary CAs were cored at 1.5 mm diameter and transferred to the microarray block. Immunohistochemistry (IHC) was performed using anti-EGFR, -VEGF, and -HIF 1a monoclonal antibodies. Concerning EGFR, quantitative evaluation was based on a semi-automated analysis system. Chromogenic in situ hybridization (CISH) was performed using EGFR gene and chromosome 7 centromeric probes. RESULTS: Protein overexpression was observed in 13/60 (21.6%), 45/60 (75%) and 7/60 (11.6%) cases regarding EGFR, VEGF, and HIF 1a, respectively. CISH analysis detected 4/60 (6.6%) EGFR gene amplified cases, whereas chromosome 7 aneuploidy was identified in 11/60 (18.3%) cases. Significant associations raised correlating stage to chromosome 7 (p=0.024), HIF 1a expression to tumor anatomical location (p=0.019) and also VEGF to HIF 1a expression (p=0.001), whereas EGFR expression was not associated to EGFR gene copies. CONCLUSION: According to our results, chromosome 7 instability is correlated to advanced disease, whereas a significant subset of CAs demonstrates an alternative, non- HIF 1a depended mechanism of VEGF overexpression. Furthermore, EGFR protein overexpression does not predict a specific gene deregulation mechanism.

Acute intermittent porphyria in pregnancy: a common misdiagnosis.

Acute intermittent porphyria (AIP) is inherited in an autosomal dominant fashion. Only 10% to 15% of the gene carriers have the clinical syndrome. The prevalence of AIP in Europe is 1/20,000. Pregnancy represents an essential risk factor in patients suffering from AIP. The clinical syndrome in AIP presents mainly with acute attacks, especially during the first trimester. Misdiagnosis of AIP unfortunately is very common. Pregnancy in women with AIP is associated with higher rates of spontaneous abortion, hypertension, low birth weight infants and considerable mortality (2-42%). Pregnancy, despite the major hormonal alterations it causes, is seldom associated with porphyric symptoms. There are only limited reports supporting the use of hemin during pregnancy, but experience indicates that it can be safely administered in pregnant women. Until clinical improvement is achieved, symptomatic treatment is recommended. Despite the fact that pregnancy in women suffering from AIP is related to higher rates of morbidity and complications, close management throughout the pregnancy could ensure a good outcome.

Self-injurious behavior among Greek male prisoners: prevalence and risk factors.

BACKGROUND: Self-harm among prisoners is a common phenomenon. This study aims to estimate the prevalence of self-injurious behavior (SIB) among Greek male prisoners, record their motives and determine independent risk factors. METHODS: A self-administered, anonymous questionnaire was administered to 173 male prisoners in the Chalkida prison, Greece. The questionnaire included items on self-harm/SIB, demographic parameters, childhood history, family history, physical and mental disease, lifestyle and smoking habits, alcohol dependence (CAGE questionnaire), illicit substance use, aggression (Buss-Perry Aggression Questionnaire [BPAQ] and Lifetime History of Aggression [LTHA]), impulsivity (Barrat Impulsivity Scale-11) and suicidal ideation (Spectrum of Suicidal Behavior Scale). Univariate nonparametric statistics and multivariate ordinal logistic regression were performed. RESULTS: Of all the participants, 49.4% (95% CI: 41.5-57.3%) disclosed self-harm (direct or indirect). The prevalence of SIB was equal to 34.8% (95% CI: 27.5-42.6%). Most frequently, SIB coexisted with indirect self-harm (80.7%). The most common underlying motives were to obtain emotional release (31.6%) and to release anger (21.1%). At the univariate analysis, SIB was positively associated with a host of closely related factors: low education, physical/sexual abuse in childhood, parental neglect, parental divorce, alcoholism in family, psychiatric condition in family, recidivism, age, sentence already served, impulsivity, aggression, alcohol dependence, self-reported diagnosed psychiatric condition and illicit substance use. Childhood variables were particularly associated with the presence of diagnosed psychiatric condition. At the multivariate analysis, however, only three parameters were proven independent risk factors: self-reported diagnosed psychiatric condition, illicit substance use and aggression (BPAQ scale). CONCLUSION: The prevalence of SIB is particularly high. Psychiatric condition, illicit substance use and aggression seem to be the most meaningful risk factors; childhood events seem only to act indirectly.

Needle tract seeding after vacuum-assisted breast biopsy.

BACKGROUND: A matter of substantial concern regarding all needle biopsy techniques is seeding along the biopsy needle tract. PURPOSE: To assess cell seeding along the needle tract of vacuum-assisted breast biopsy (VABB). MATERIAL AND METHODS: The study included 21 patients with ductal carcinoma in situ (DCIS) and 10 patients with invasive ductal carcinoma (IDC) diagnosed by VABB for nonpalpable mammographic lesions. VABB (11G, on a Fischer table) was performed, and the duration of the procedure was measured. After surgery, the whole needle tract was embedded in paraffin blocks, stained with hematoxylin-eosin, and examined by a pathologist. RESULTS: Cases with dissemination of cancer cells in the needle tract were not observed (one-sided 97.5% CI 0-10.0%). In 2/31 (6.5%) cases (95% CI 0.8-21.4%), benign epithelial cell displacement was observed, and the duration of VABB was significantly longer in these two cases (52.5+/-3.5 min vs. 42.0+/-4.4 min for cases without benign cell displacement; P = 0.018, Mann-Whitney-Wilcoxon test for independent samples). CONCLUSION: No displacement of malignant cells within the 11G needle tract was documented. Benign cell displacement was associated with longer VABB duration. The phenomenon of tumor cell dissemination along the needle tract is of questionable clinical significance when the treatment guidelines are followed.