<p>Supplementary Material and Methods, Results, 1 figure, and 1 table</p>

Hepatic adenomas are uncommon benign tumours of the liver which may eventually present with acute onset following rupture of the lesion and haemorrhage. We present here a unique case of strangulated adenoma of the liver presenting as acute abdomen. A 27-year-old woman taking oral contraceptives, presented to the emergency department with abdominal pain, palpable abdominal mass, fever, and neutrophilia. An abdominal ultrasound showed a 3-cm hepatic nodule and an 11-cm mesogastric mass. Computed tomography of the abdomen revealed a 2.3-cm liver adenoma and a 13-cm pedunculated mass of the liver showing no contrast enhancement suggestive of pedicle torsion with ischemia of the mass. The patient underwent an emergent open resection of the strangulated liver mass, she recovered without complications, and was discharged home after three days. Final pathology confirmed an hepatocellular adenoma with areas of necrosis and hemorrhage. The clinical significance of the disease is discussed.

BACKGROUND:Multiple sclerosis (MS) is a complex disorder thought to result from an interaction between environmental and genetic predisposing factors which have not yet been characterised, although it is known to be associated with the HLA region on 6p21.32. Recently, a picture of chronic cerebrospinal venous insufficiency (CCSVI), consequent to stenosing venous malformation of the main extra-cranial outflow routes (VM), has been described in patients affected with MS, introducing an additional phenotype with possible pathogenic significance.METHODS:In order to explore the presence of copy number variations (CNVs) within the HLA locus, a custom CGH array was designed to cover 7 Mb of the HLA locus region (6,899,999 bp; chr6:29,900,001-36,800,000). Genomic DNA of the 15 patients with CCSVI/VM and MS was hybridised in duplicate.RESULTS:In total, 322 CNVs, of which 225 were extragenic and 97 intragenic, were identified in 15 patients. 234 known polymorphic CNVs were detected, the majority of these being situated in non-coding or extragenic regions. The overall number of CNVs (both extra- and intragenic) showed a robust and significant correlation with the number of stenosing VMs (Spearman: r = 0.6590, p = 0.0104; linear regression analysis r = 0.6577, p = 0.0106). The region we analysed contains 211 known genes. By using pathway analysis focused on angiogenesis and venous development, MS, and immunity, we tentatively highlight several genes as possible susceptibility factor candidates involved in this peculiar phenotype.CONCLUSIONS:The CNVs contained in the HLA locus region in patients with the novel phenotype of CCSVI/VM and MS were mapped in detail, demonstrating a significant correlation between the number of known CNVs found in the HLA region and the number of CCSVI-VMs identified in patients. Pathway analysis revealed common routes of interaction of several of the genes involved in angiogenesis and immunity contained within this region. Despite the small sample size in this pilot study, it does suggest that the number of multiple polymorphic CNVs in the HLA locus deserves further study, owing to their possible involvement in susceptibility to this novel MS/VM plus phenotype, and perhaps even other types of the disease.

In the attempt to reduce postoperative complications and costs and improve outcomes, the concept of fast track surgery has been proposed. Improvements in anesthesia techniques and a better understanding of the pathophysiologic events occurring during and after surgery have made it possible. A group of patients undergoing colorectal resections with a fast track approach were investigated; specifically, the effects on postoperative morbidity, resumption of intestinal function, and duration of hospitalization. Fifty patients were managed according to a protocol, which included epidural analgesia, early ambulation, and oral feeding (fast track group); they were compared with 50 patients managed with a different protocol: no epidural analgesia, early ambulation, and early oral diet (control group). Primary outcome end-points reported include morbidity, time to passage of flatus and stool, and length of hospital stay. Fourteen complications occurred in the fast track group and 13 in the control group (P = not significant (NS)). Resumption of intestinal function occurred after 3 days, and length of hospital stay was 5 days in the fast track group compared with 4 and 7 days respectively in control patients (P = NS, P < 0.01). Patients undergoing elective colorectal resections can be managed safely with fast track protocols reducing hospital stay.

Objective: Role of superficial venous surgery in reducing the time it takes for ulcers to heal is still controversial, although all studies confirm a significant reduction in ulcer recurrences. Recently, the HFE-C282Y and FXIII-V34L gene variants demonstrated a role in the risk of venous ulceration in primary chronic venous disorder (CVD) and in modulating lesion size in chronic venous ulcer (CVU), respectively. This study was conducted to investigate the role of HFE-C282Y and FXIII (V34L and P564L) gene variants in ulcer healing time after superficial venous surgery, by assessing the outcome of a cohort of homogeneous CVU patients.Methods: The study selected 91 patients affected by primary CVU (CEAP C6, Ep, Asp, Pr), with the exclusion of any other comorbidity factor involved in delayed healing process, who underwent surgery. We assessed the ulcer area and the healing time. Patients were genotyped by polymerase chain reaction for FXIII (V34L and P564L) and for HFE-C282Y substitutions.Results: Globally, CVU cases had a postoperative mean healing time of 8.5 +/- 5.7 weeks. For the subset of cases above and below the median value (M = 8.0 weeks), FXIII-V34L genotype distribution significantly differed (P < .0001). In addition, Kaplan-Meier analysis yielded specific healing time profiles for the different FXHI-V34L classes of genotype (P = .00001), with an increased risk of delayed healing for the FXIII-VV genotype (hazard ratio, 4.14; 95% confidence interval, 2.1 to 8.2; P = .00005). Although FXIII-P54L genotype distributions did not differ, homozygous 564LL cases (P=.005) and double carriers for both FXIII variants (P < .0001), had a significantly reduced healing time vs wild types. No differences in healing time were observed between carriers and noncarriers of the HFE-C282Y variant, whereas when these cases were stratified by FXIII-V34L genotypes, the L34 carriers had a significantly shorter healing time, irrespective of the HFE genotype.Conclusion: The FXIII-34L variant was significantly associated with shorter healing time after superficial venous surgery, suggesting a role in the healing and tissue regeneration phases. Conversely, HFE-C282Y, despite its role in ulcer establishment, did not affect the postoperative healing time. In perspective, the identification of patients with a poor prognosis may give clinicians the opportunity to modify management

We evaluated the incidence of sentinel lymph nodes (SLNs) in the internal mammary chain, calculated the lymphoscintigraphy and surgical detection rates, and evaluated the clinical effect on staging and the therapeutic approach in patients with breast cancer.

Following laparotomy, almost 95% of patients develop adhesions. To prevent adhesion formation, peritoneal lavage has been investigated and many different lavage solutions have been proposed. In this study, different peritoneal lavage solutions were evaluated, testing their ability to prevent adhesion formation. Three consecutive steps were followed: ( 1) The lethal dose of Eschericia coli injected in the rat peritoneal cavity was determined, ( 2) the morbidity and mortality rates of different solutions for peritoneal lavage (i.e., saline, twice-distilled water, antiseptics, and antibiotics solutions) was investigated, and ( 3) the capability of the different lavage solutions to prevent adhesion formation was tested. Two hundred and ninety-eight rats were employed in this study. After intraperitoneal injection of E. coli, infection ( clinical signs and animal vitality), adhesion formation ( explorative laparoscopy, peritoneumgraphy and Zuhlke scale grading), and animal performance status were investigated. All differences were evaluated by chi-square and analysis of variance ( ANOVA) tests. Saline solution showed a low morbidity rate with no deaths. Twice-distilled water was associated with 100% mortality rate, as opposed to 45 - 75% for antiseptics, and 0 - 3% mortality for antibiotics. Antibiotics determined higher adhesion formation by Zuhlke score as compared to saline solution ( p <.001), while no difference was observed between antiseptics and saline ( p = NS). Peritoneal lavage with 37 degrees C saline solution was associated with low adhesion formation and high survival rate as compared to twice-distilled water and antiseptics. Antibiotics solutions had high survival rate and high adhesion formation. Twice-distilled water and antisepsis should be avoided when based on the data obtained in this work.

Matrix metalloproteinases (MMPs) are overexpressed in venous leg ulcers, determining a breakdown of the main extracellular matrix (ECM) components owing mainly to collagenase activities, and so playing a crucial role in ulcer pathogenesis. The authors studied the effects of coagulation factor XIII (FXIII), which cross-links collagen and other ECM components, in human fibroblast cultured cells in the presence and in the absence of matrix metalloproteinases from Clostridium histolyticum collagenase. Clostridium collagenase at concentrations of 2.0, 1.0, and 0.5 mg/mL was added to normal human dermal fibroblasts cultured in the presence of 0.0, 1.0, and 5.0 U/mL of FXIII concentrate (Fibrogammin P, Aventis Behring). Cell counting and metabolically active fibroblast evaluation in the cultures were monitored for 72 hours, by means of trypan-blue dye and MTT test, respectively. The MTT test showed that at the highest collagenase concentration (2.0 mg/mL), the cell number decreased more than 95% in 72 hours of treatment and no significant differences were observed regardless of the FXIII concentrations utilized. At lower collagenase concentration (1.0 mg/mL), in absence or in presence of FXIII (1.0 U/mL), the cell number decreased by about 80% in 72 hours. In contrast, in the presence of higher FXIII levels (5.0 U/mL), cells suffered globally significantly less collagenase effects (p=0.011) and the gain was appreciable at each time tested. Finally, at 0.5 mg/mL of collagenase concentration, in the absence of FXIII, the cell number decreased by about 60% in 72 hours, whereas in presence of FXIII 1.0 U/mL and 5.0 U/mL, cells decreased significantly less, by about 35% and 20%, respectively (p<0.025 and p<0.01, respectively). These data were also confirmed by direct cell counting utilizing the trypan-blue test. Factor XIII contrasts effectively the detrimental action of Clostridium collagenases in human fibroblast cultured cells. These results support several in vivo reports about the effectiveness of its topical application in order to enhance the venous ulcer healing processes.

Background: Gene promoter methylation is a mechanism for tumor suppressor gene silencing and inactivation. The development of highly sensitive methods for revealing aberrant cancer-associated DNA methylation allows the identification of tumor markers not only in tumor samples, but also in body fluid, an approach that can be useful in the early detection of neoplasms. Methods: We analyzed the methylation status at 16 loci in tumor samples of the gastrointestinal tract and in early or pre-neoplastic lesions of the colon. Results: Tumor samples revealed that methylation at the transmembrane protein containing epidermal growth factor and follistatin domains (TPEF) locus had the best ratio of discrimination between tumor samples versus normal tissues (83 versus 0%). Its combination with hypermethylated in cancer 1 (HIC1) , death-associated protein kinase (DAPK) and O -6-methylguanine DNA methyltransferase (MGMT) , allowed the detection of aberrant methylation in 98% of colorectal carcinomas and 100% of gastric carcinomas. The same alterations were also detected in colon adenomas and tissues surrounding the adenomas, indicating that hypermethylation at these loci occurred early in tumor progression. Analysis of DNA from peripheral blood revealed that TPEF methylation was detectable in colorectal tumor patients and patients with early or pre-neoplastic lesions, but not in healthy volunteers. Conclusions: Our results identify TPEF as a tumor marker that could be useful in the follow-up of gastrointestinal cancer patients or the screening of individuals at risk of developing gastrointestinal neoplasms.