Fibrin sealant agents: clinical application of TachoSil® in abdominal surgery. Six years experience in an emergency surgery department and review of the literature.

BACKGROUND: The success of every surgical procedure depends on an appropriate hemostatis. Topical haemostatic agents, like fibrin sealants, are an option for providing haemostasis and may be particularly useful for complex injuries. AIM: The aim of the study is to evaluate the use of TachoSil® in abdominal surgery and its benefits to prevent bleedings, and to establish its fields of use. METHODS: A retrospective observational study was performed on 308 patients underwent to emergency surgery with TachoSil®'s application into our department between January 2012 and March 2018. RESULTS: After the application of the hemostatic device there have been no haemorrhagic complications that have needed a second surgical intervention. Most frequently use of TachoSil® was in the gallbladder bed after cholecystectomy for an acute cholecystitis. CONCLUSIONS: Our experience, supported by other reports in the literature, suggests the use of TachoSil® may provide an effective option in helping to control bleedings.

Dietary Patterns and Retinal Vessel Caliber in the Irish Nun Eye Study.

BACKGROUND: Retinal vessel abnormalities are associated with cardiovascular disease risk. Widening of retinal venules is associated with increased risk of stroke while narrowing of retinal arterioles independently predicts incident hypertension, coronary heart disease and diabetes. Dietary factors are known to play an important role in cardiovascular health. However, few studies have examined the association between dietary patterns (DPs) and retinal microvascular health. OBJECTIVE: To examine the association between 'a posteriori'-derived DPs and retinal vascular caliber (RVC) in older women with a restricted lifestyle. METHODS: This was a cross-sectional study of 1233 participants (mean age: 76.3 years) from the Irish Nun Eye Study (INES). Computer-assisted software was used to measure RVC from digital eye images using standardized protocols. Dietary intake was assessed using a food frequency questionnaire (FFQ). DP analysis was performed using principal component analysis from completed FFQs. Regression models were used to assess associations between DPs and retinal vessel diameters, adjusting for age, body mass index, refraction, hypertension, diabetes mellitus, ischemic heart disease, cerebrovascular accident and fellow eye RVC. RESULTS: Two DPs were identified: a 'healthy' pattern with high factor loadings for fruit, vegetables, wholegrains and oily fish and an 'unhealthy' pattern with high factor loadings for sugar and sweets, chips, high fat dairy products and French fries. Adjusted linear regression analysis revealed that those who adhered most closely to the unhealthy DP had wider central retinal venular equivalent (CRVE) (p=0.03) and narrower central retinal arteriolar equivalent (CRAE) (p=0.01) compared to the least unhealthy DP. No independent relationship was observed between the healthy DP and RVC. CONCLUSION: In this cohort of older women with a restricted lifestyle, an unhealthy DP was independently associated with an unfavorable retinal profile, namely a widening of retinal venules and narrowing of retinal arterioles.

Neuroendocrine tumor of the common bile duct: case report.

Neuroendocrine tumors (NET) are a very heterogeneous group of neoplasms; in recent years we have seen an increase in their incidence (3.65 /100.000/year). They can be associated with hereditary endocrine syndromes (MEN, Von Hippel Lindau); they can occur at any age and the incidence is slightly higher in men than women. The aetiology of the neuroendocrine tumors is unclear; in most cases, inflammation of the bile ducts may be the underlying cause and for this reason, the initial patient's evaluation should be focused on the different aspects concerning the oncological one and the possible sequelae of the biliary obstructions that can evolve in biliary sepsis. All neuroendocrine tumors have malignant potential. The most frequent sites of extrahepatic biliary NETs are the common hepatic duct and the distal common bile duct (19.2%), followed by the middle of the common bile duct (17.9%), the cystic duct (16.7%), and the proximal common bile duct (11.5%). We can divide them into: well-differentiated and poorly differentiated. Considering the clinical features, neuroendocrine tumors can be divided into functional and non-functional. As regards the staging, we distinguish localized, regional and metastatic tumors. Tumors derived from the bile duct are difficult to diagnose preoperatively, mainly because of its low incidence and difficult diagnostic process. However since cholangiocarcinomas account for about 80% of all primary biliary tumors, it is important to think about other options despite their low frequency when a patient presents with abnormal characteristics. The most sensitive immunohistochemical markers are expressing neuron-specific enolase, synaptophisin and chromogranin A. Liver function tests, alkaline phosphatase and bilirubin are often high. Sometimes an anemia can appear in the presence of a chronic disease or in patients with more advanced disease. It is known that the measurement of chromogranin A is useful for the preoperative diagnosis of neuroendocrine tumors. Chromogranin A is elevated in 90% of neuroendocrine tumors of the intestine, and the levels correlate with tumor burden and the possibility of recurrence and, therefore, chromogranin A can be an effective biological marker for preoperative diagnosis of neuroendocrine tumors. Bile endocrine tumors remain silent until metastasizing or growing into neighboring organs, because of its uncommon diagnosis in early stages due to its low incidence, absence of serum markers and lack of symptoms related to the hormonal pattern. Preoperative diagnosis of common bile duct carcinoma is extremely difficult, because it is foretold by non-specific symptoms that include pain or discomfort in the right upper quadrant level and weight loss. A 51- year-old woman presented a jaundice and severe bile duct dilatation. The enhanced CT scan showed a mass, approximately 15 mm in diameter, in the distal common biliary duct. The MRI and ERCP confirmed the mass. Cromogranin A value was negative. The diagnosis of well differentiated endocrine tumor of the biliary tract was done after its surgical resection was performed. The postoperative period was uneventful. Extrahepatic biliary NETs are rare, and extrahepatic bile ducts reportedly account for only 0.32% of primary NET sites. The prognosis for NET of the bile duct appears to be poor.

Association of SULT1A1 Arg²¹³His polymorphism with male breast cancer risk: results from a multicenter study in Italy.

Male breast cancer (MBC) is rare and poorly understood. Like female breast cancer (FBC), MBCs are highly sensitive to hormonal changes, and hyperestrogenism, specifically, represents a major risk factor for MBC. MBC is considered similar to late-onset, post-menopausal estrogen/progesteron receptors positive FBC (ER+/PR+). Sulfotransferase 1A1 (SULT1A1) is an enzyme involved in the metabolism of estrogens. Recently, SULT1A1 common functional polymorphism Arg(213)His (638G>A) variant has been found to be associated with increased breast cancer (BC) risk, particularly in post-menopausal women. For this reason, we decided to explore whether SULT1A1 Arg(213)His could exert an effect on MBC development. The primary aim of this study was to evaluate the influence of the SULT1A1 Arg(213)His polymorphism on MBC risk. The secondary aim was to investigate possible associations with relevant clinical-pathologic features of MBC. A total of 394 MBC cases and 786 healthy male controls were genotyped for SULT1A1 Arg(213)His polymorphism by PCR-RFLP and high-resolution melting analysis. All MBC cases were characterized for relevant clinical-pathologic features. A significant difference in the distribution of SULT1A1 Arg(213)His genotypes was found between MBC cases and controls (P < 0.0001). The analysis of genotype-specific risk showed a significant increased MBC risk in individuals with G/A (OR 1.97, 95% CI 1.50-2.59; P < 0.0001) and A/A (OR 3.09, 95% CI 1.83-5.23; P < 0.0001) genotypes in comparison to wild-type genotype, under co-dominant model. A significant association between SULT1A1 risk genotypes and HER2 status emerged. Results indicate that SULT1A1 Arg(213)His may act as a low-penetrance risk allele for developing MBC and could be associated with a specific tumor subtype associated with HER2 overexpression.

Atherosclerotic coronary plaque in subjects with diabetic neuropathy: the prognostic cardiovascular role of Charcot neuroarthropathy--a case-control study.

The aim of this study was to investigate the severity of coronary artery disease (CAD) and the plaque composition in neuropathic type 2 diabetic subjects with and without Charcot neuroarthropathy (CN) undergoing multidetector computed tomography coronary angiography (MDCT-CA). The study was a single-center, observational, with unmatched case-control design. We selected 17 CN patients and 18 patients with diabetic neuropathy (DN) without CN. In all the patients, multidetector computed tomography was performed to assess the coronary artery calcium score (CACS) and degree of coronary artery stenosis. Patients were classified as positive in the presence of significant CAD if there was at least one stenosis >50 % on MDCT-CA. The invasive coronary angiography was performed in case of significant stenosis detected with MDCT-CA, both as reference to standard and eventually as treatment. Groups were matched for age, sex, and traditional CAD risk factors. As compared to DN individuals, CN exhibited higher rates of significant coronary stenoses (p = 0.027; OR 7.7 [1.3-43.5]). However, no significant differences were observed in the CACS, which reflects plaque burden, in the two groups (p = 0.759). No significant differences were observed comparing CACS distribution in all subjects for stenosis higher/equal or lower than 50 % (p = 0.320). Finally, no significant differences were observed comparing CACS distribution in CN and DN subjects for coronary stenoses higher/equal or lower than 50 %. Our results suggest that CN patients have a higher prevalence of severe coronary plaques compared to DN patients. Nevertheless, coronary plaques in CN patients did not exhibit an increased degree of calcification.

Male breast cancer: genetics, epigenetics, and ethical aspects.

BACKGROUND AND STUDY DESIGN: Male breast cancer (MBC) is a rare disease compared with female BC and our current understanding regarding breast carcinogenesis in men has been largely extrapolated from the female counterpart. We focus on differences between the ethical issues related to male and female BC patients. A systematic literature search by using PubMed (http://www.ncbi.nlm.nih.gov/pubmed/), was carried out to provide a synopsis of the current research in the field of MBC genetics, epigenetics and ethics. Original articles and reviews published up to September 2012 were selected by using the following search key words to query the PubMed website: 'male breast cancer', 'male breast cancer and genetic susceptibility', 'male breast cancer and epigenetics', 'male breast cancer and methylation', 'male breast cancer and miRNA', 'male breast cancer and ethics'. RESULTS AND CONCLUSIONS: As in women, three classes of breast cancer genetic susceptibility (high, moderate, and low penetrance) are recognized in men. However, genes involved and their impact do not exactly overlap in female and male BC. Epigenetic alterations are currently scarcely investigated in MBC, however, the different methylation and miRNA expression profiles identified to date in female and male BCs suggest a potential role for epigenetic alterations as diagnostic biomarkers. Overall, much still needs to be learned about MBC and, because of its rarity, the main effort is to develop large consortia for moving forward in understanding MBC and improving the management of MBC patients on a perspective of gender medicine.

Association of low-penetrance alleles with male breast cancer risk and clinicopathological characteristics: results from a multicenter study in Italy.

It is well-known that male breast cancer (MBC) susceptibility is mainly due to high-penetrance BRCA1/2 mutations. Here, we investigated whether common low-penetrance breast cancer (BC) susceptibility alleles may influence MBC risk in Italian population and whether variant alleles may be associated with specific clinicopathological features of MBCs. In the frame of the Italian Multicenter Study on MBC, we genotyped 413 MBCs and 745 age-matched male controls at 9 SNPs annotating known BC susceptibility loci. By multivariate logistic regression models, we found a significant increased MBC risk for 3 SNPs, in particular, with codominant models, for rs2046210/ESR1 (OR = 1.71; 95 % CI: 1.43-2.05; p = 0.0001), rs3803662/TOX3 (OR = 1.59; 95 % CI: 1.32-1.92; p = 0.0001), and rs2981582/FGFR2 (OR = 1.26; 95 % CI: 1.05-1.50; p = 0.013). Furthermore, we showed that the prevalence of the risk genotypes of ESR1 tended to be higher in ER- tumors (p = 0.062). In a case-case multivariate analysis, a statistically significant association between ESR1 and ER- tumors was found (OR = 1.88; 95 % CI: 1.03-3.49; p = 0.039). Overall, our data, based on a large and well-characterized MBC series, support the hypothesis that common low-penetrance BC susceptibility alleles play a role in MBC susceptibility and, interestingly, indicate that ESR1 is associated with a distinct tumor subtype defined by ER-negative status.

Drusen prevalence and pigmentary changes in Caucasians aged 18-54 years.

AIMS AND PURPOSE: The aim of this study was to describe the prevalence and characteristics of drusen and pigmentary changes in a middle-aged population. METHODS: Retinal images from 500 individuals aged 18-54 years were included. The source of participants was two UK optometry practices. Retinal images were graded using the Wisconsin Age-Related Maculopathy Grading System. However, owing to the relatively young age of the population studied, a new category of drusen of smaller size (<31.5 µm) was introduced. RESULTS: Drusen were identified within the central macular grid in 91.48% of all gradable eyes and in 444 subjects. Drusen sized <31.5 µm were present in 89.7% of eyes, drusen sized >31.5 µm and <63 µm were present in 45.9% of all eyes and drusen >63 µm and <125 µm were present in only 1.7% of eyes. No eye had drusen larger or equal to 125 µm. Very few eyes (1.2%) showed pigmentary changes within the grid. Drusen load increased with increasing age, P <0.001. CONCLUSIONS: The frequency of drusen in a younger Caucasian population aged 18-54 years is high, with 91.48% of all gradable eyes having drusen. The most frequent drusen subtype was hard distinct drusen <31.5 µm. No druse greater or equal in size to 125 µm was seen. Pigmentary changes are rare.

Ectopic liver nodules: a rare finding during cholecystectomy.

The ectopic liver (or choristoma) is a rare condition found during autopsy or abdominal exploration for various indications. The authors report two cases of ectopic liver found during laparoscopic cholecystectomy for acute cholestytis. The ectopic liver tissue has been reported to develop in several sites as thoracic cavity, gastrohepatic ligament, adrenal glands, pancreas, esophagus and, above all, gallbladder. The Authors review the literature and report their experience as a contribution to the knowledge of this rare pathological entity.

[Doctor or technician? Reflections on the medical professional today]. / Tecnici o medici? Riflessioni sulla professione medica oggi.

Medicine is an outstanding example of an empirical science in theory and practice. In every stage of his work a doctor should be ready to pick up signs of possible scientific progress. Being constantly attentive and able to see anything new occurring, however difficult it may be to discern, should remain the basis of any professional commitment that takes care not to become sterile and thereby less effective in treating disease. A doctor is an experimenter par excellence, one who constantly applies experimental methods based on his own ''historical'' knowledge, experience, and capacity to comprehend even the tiniest signals that reach him from the real world. On the other hand, although the indiscriminate acceptance of results obtained by clinical trials and the increasing recourse to technology could herald the end of clinical freedom, we believe that such recourse to technology is, in fact, desirable. The reason for this belief is that a lack of innovation leads to loss of enthusiasm and loss of interest in specific clinical problems; it also results in a cultural attitude that refutes the notion of experimental logic being inherent in any treatment because of the changeability of individual conditions on a biological, clinical, and psycho-relational level.

Multi-scale analysis of the toraymyxin adsorption cartridge. Part I: molecular interaction of polymyxin B with endotoxins.

Endotoxins or lipopolysaccharides are the main constituents of the outer leaflet of Gram-negative bacteria membrane and play a central role in the pathogenesis of the septic shock. Polymyxin B has both antibacterial and antiendotoxin capability; indeed it is able to destroy the bacterial outer membrane and bind endotoxin neutralizing its toxic effects. Cartridges containing polymyxin B-immobilized fibers (Toraymyxin PMX-F, Toray Industries, Japan) are used in extracorporeal hemoperfusion to remove circulating endotoxin. The aim of this study is the characterization of the polymyxin B-endotoxin system at the molecular level, thus providing quantitative evaluation of the binding forces exerted in the molecular complex. Polymyxin B was interfaced with five molecular models of lipopolysaccharides differing in their structure and molecular mechanics simulations were performed at different intermolecular distances aimed at calculating the interaction energies of the complex. Binding forces were calculated by fitting interaction energies data. Results show that in the short range the polymyxin B-endotoxin complex is mediated by hydrophobic forces and in the long range the complex is driven by ionic forces only. From a mechanical standpoint, polymyxin B-endotoxin complex is characterized by maximum binding forces ranging between 1.39 nN to 3.79 nN. The knowledge of the binding force behavior at different intermolecular distances allows further investigations at higher scale level (Part II).

Levels of anxiety and pain during chemotherapy with peripheral versus central vascular access: an experimental evaluation.

PURPOSE: The purpose of this research was to evaluate pain and anxiety levels in patients undergoing chemotherapy via central venous catheter (CVC) and peripheral venous access (PVA). METHOD: The sample consisted of 56 cancer patients undergoing at least one chemotherapy treatment cycle. They were divided into two groups based on the administration method of the chemotherapeutic drug: the experimental group (patients with CVC) and the control group (patients with PVA). The instruments used were the following: for multidimensional pain evaluation the Italian Pain Questionnaire (QUID, devised by De Benedettis et al), and the Visual Analogue Scale (VAS) Chart of Pain. To evaluate the state and anxiety traits, the State-Trait Anxiety Inventory (STAI questionnaire, by D. Spielberg) was used, and we used structured interviews for the statistical survey. RESULTS: Analyzing the data from the STAI questionnaire, it appeared that the state-trait anxiety levels of the experimental group and the control group were not significantly different (analysis of the mean difference made using the Student's t-test). The average scores of the STAI questionnaire for both groups fell within the normal range. This indicated that the anxiety level was unaffected by the introduction of the device (the CVC). The data collected with the QUID questionnaire and subsequent statistical analysis demonstrated that the difference between the means (Student's t-test) of the experimental group and the control group was significantly lower, as regards perception of the sensorial and evaluative quality of pain (p=0.05) in the experimental group. From the evaluation of the VAS method, it appeared that the difference between the means was not significant in either group, although the distribution of frequency tended towards lower values in the experimental group with respect to the control group. This confirms previous QUID research where a lower pain level is recorded. CONCLUSIONS: Analysis of the data collected via the structured interview revealed that most of the CVC sample did not respond to catheter insertion as a sign of a worsening of their illness.

Quantitation by competitive PCR assay of vascular endothelial growth factor in non-small cell lung carcinomas.

The vascular endothelial growth factor (VEGF) is known to be one of the most important angiogenic factors under both physiological and pathological conditions. The VEGF overexpression by a wide spectrum of neoplastic diseases has suggested an important role of this cytokine in tumor-neovascularization. A method is described for quantification by reverse transcription-polymerase chain reaction (RT-PCR) of VEGF mRNA in non-small cell lung cancer tissues (NSCLC). The method entails addition to the sample of competitor DNA molecules that share the same primer recognition sites as the amplified target, but which can be easily distinguished by gel electrophoresis because of their different lengths (competitive PCR). We analyzed the VEGF mRNA expression level in 34 cases of lung tumor tissues compared to the respective adjacent normal tissues. In 4 out of 34 (11.7%) analyzed couples there was no VEGF mRNA expression, in 8 out of 34 (23.5%) only normal parenchymal tissue was positive for VEGF mRNA expression; in the remaining 22 cases (64. 7%) both normal and tumor tissues showed PCR products for VEGF. In 17 out of these 22 couples (77.2%) a higher number of VEGF mRNA molecules were present in tumor specimens than in the normal counterpart. According to these results, the competitive PCR-method seems to provide a useful tool for the quantitate VEGF expression in order to identify its role in the development of lung cancer.

Bcl2 and p53 regulate vascular endothelial growth factor (VEGF)-mediated angiogenesis in non-small cell lung carcinoma.

The aim of this study was to investigate the expression of p53 and bcl2 proteins in a series of 107 non-small cell lung cancers (NSCLC), and to relate such protein expression to neovascularisation and the expression of vascular endothelial growth factor (VEGF). Moreover, we analysed the prognostic impact of these biological parameters on overall survival, both in univariate and multivariate analyses. An inverse association was found between bcl2 expression and microvessel count (MVC; P = 0.0004) and bcl2 and VEGF (P = 0.007). In contrast, a significant association was found between p53 expression and MVC (P = 0.03) and p53 and VEGF expression (P = 0.04). In univariate analysis, nodal status (P < 0.000001), MVC (P < 0.000001), bcl2 (P = 0.002), p53 (P = 0.03) and VEGF expression (P < 0.000001) significantly affected overall survival, but in multivariate analysis only MVC and VEGF expression retained their prognostic influence. Our results suggest that bcl2 and p53 possibly control the development of tumour angiogenesis in NSCLC, with putative mediation by VEGF. Moreover, the important influence of angiogenesis in the progression of NSCLC is further highlighted.

Evaluation of epidermal growth factor-related growth factors and receptors and of neoangiogenesis in completely resected stage I-IIIA non-small-cell lung cancer: amphiregulin and microvessel count are independent prognostic indicators of survival.

We have determined the expression of transforming growth factor alpha (TGF alpha), amphiregulin (AR), CRIPTO, the epidermal growth factor receptor (EGFR), erbB-2, erbB-3, and tumor angiogenesis in a series of 195 patients with stage I-IIIA non-small cell lung cancer (NSCLC) treated with radical surgery to define their usefulness as prognostic indicators of survival. A variable degree of specific staining in cancer cells was observed for the three growth factors and for the three growth factor receptors in the majority of NSCLC patients. A statistically significant association between overexpression of TGF alpha, AR, and CRIPTO was observed. Enhanced expression of AR was significantly correlated with enhanced expression of erbB-2 and advanced T-stage. A direct association was also detected for overexpression of TGF alpha and of erbB-2 or erbB-3, respectively. Sex, tumor size, nodal status, stage, microvessel count, as a measure of neovascularization, and AR overexpression significantly correlated with overall survival at univariate analysis. In a Cox multivariate analysis, the only characteristics with an independent prognostic effect on OAS were microvessel count [relative hazard (RH), 6.61; P < 0.00001), nodal status (RH, 1.59; P = 0.0013), and AR overexpression (RH, 1.72; P = 0.02). These results suggest that evaluation of neoangiogenesis and of certain growth factors, such as AR, can be useful in addition to conventional pathological staging to select high-risk NSCLC patients who may benefit from post-surgical systemic therapies.

Videoconferencing as a medical educational tool: first experience in Argentinean public hospital.

Authors present their experience with first medical videoconferencing program developed in a public Argentinean hospital. Both modalities--room and desktop videoconferencing--were used. The program was exclusively used for educational purposes. A total of twelfth videoconferencing were successfully made using all resources. They included surgical procedures, magisterial lessons, grand rounds, etc. The project proved that videoconferencing is a cost-effective medical education tool, even in developing countries.