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Background The widespread nature of coronavirus disease 2019 (COVID-19) has been unprecedented. We sought to analyze its global impact with a survey on colorectal cancer (CRC) care during the pandemic. Methods The impact of COVID-19 on preoperative assessment, elective surgery, and postoperative management of CRC patients was explored by a 35-item survey, which was distributed worldwide to members of surgical societies with an interest in CRC care. Respondents were divided into two comparator groups: 1) ‘delay’ group: CRC care affected by the pandemic; 2) ‘no delay’ group: unaltered CRC practice. Results A total of 1,051 respondents from 84 countries completed the survey. No substantial differences in demographics were found between the ‘delay’ (745, 70.9%) and ‘no delay’ (306, 29.1%) groups. Suspension of multidisciplinary team meetings, staff members quarantined or relocated to COVID-19 units, units fully dedicated to COVID-19 care, personal protective equipment not readily available were factors significantly associated to delays in endoscopy, radiology, surgery, histopathology and prolonged chemoradiation therapy-to-surgery intervals. In the ‘delay’ group, 48.9% of respondents reported a change in the initial surgical plan and 26.3% reported a shift from elective to urgent operations. Recovery of CRC care was associated with the status of the outbreak. Practicing in COVID-free units, no change in operative slots and staff members not relocated to COVID-19 units were statistically associated with unaltered CRC care in the ‘no delay’ group, while the geographical distribution was not. Conclusions Global changes in diagnostic and therapeutic CRC practices were evident. Changes were associated with differences in health-care delivery systems, hospital’s preparedness, resources availability, and local COVID-19 prevalence rather than geographical factors. Strategic planning is required to optimize CRC care., Global changes in both diagnostic and therapeutic practices in colorectal cancer care were evident in this survey conducted to analyze the impact of COVID-19 outbreak. The importance of this finding is that changes were associated with differences in health care delivery systems, hospital’s preparedness, resources availability, and local COVID-19 prevalence rather than geographical variations.

Background: Haemorrhoidal disease (HD) is a benign condition affecting a considerable part of adult population. HD can be considered a social and economic burden with high impact on patients’ lifestyle. Several new techniques and devices have been proposed for HD treatment; however, preoperative assessment is essential and the use of classification system is recommended. Methods:: In the last two decades many studies described the preoperative assessment and several attempts of classification for HD. This review focuses on the most relevant studies found in literature where classification systems and clinical evaluation with differential diagnosis have been evaluated. Results: The knowledge of classification systems and differential diagnosis for HD has been shown to play a central role in the clinical assessment and the best treatment choice. Although there are new challenging techniques and devices for HD treatment, a preoperative assessment is always mandatory. Conclusion: Preoperative clinical evaluation is essential for HD patient treatment and outcome. Classification systems are useful for the therapeutic choice and researches on new medical or surgical treatments. In fact, the international guidelines advise several therapeutic options depending on the severity of the HD.

Background The efficacy of sacral nerve stimulation (SNS) on patients with chronic refractory slow-transit constipation is controversial and its mechanism of action on gastrointestinal motility and transit is not fully understood. The aim of this study was to document the effects of temporary SNS on the gastrointestinal and biliary tract motility and on gastrointestinal transit in patients with refractory slow-transit constipation. Methods This was a prospective interventional study. Patients with slow-transit chronic constipation, unresponsive to any conservative treatment, were enrolled between January 2013 and December 2018. Patients’ quality of life [patient assessment of constipation quality of life (PAC-QOL) questionnaire], constipation scores (Cleveland Clinic Constipation Score) colonic transit time (CTT), orocecal transit time (OCTT), gastric and gallbladder kinetics, together with the assessment of the autonomic nerve function were evaluated before and during temporary SNS. Results 14 patients (12 females, median age 38 years, range 24–42 years) had temporary SNS. The Cleveland Clinic Constipation Score did not change compared to baseline (23 ± 3 vs 21.4; p = 070). The PAC-QOL did not improve significantly during the stimulation period. Gallbladder/stomach motility (half-emptying time) did not change significantly before and after SNS. OCTT was delayed at baseline, as compared to standard internal normal values, and did not change during SNS. CTT did not improve significantly, although in two patients it decreased substantially from 97 to 53 h, and from 100 to 65 h. Conclusions Temporary SNS did not have any effect on upper/lower gastrointestinal motility and transit in patients with severe constipation.

Breast cancer (BC) is the most common cancer and second leading cause of cancer mortality in women worldwide. Validated biomarkers enhance efforts for early detection and treatment, which reduce the risk of mortality. Epigenetic signatures have been suggested as good biomarkers for early detection, prognosis and targeted therapy of BC. Here, we highlight studies documenting the modifying effects of dietary fatty acids and obesity on BC biomarkers associated with DNA methylation. We focus our analysis on changes elicited in writers of DNA methylation (i.e., DNA methyltransferases), global DNA methylation and gene-specific DNA methylation. To provide context, we precede this discussion with a review of the available evidence for an association between BC incidence and both dietary fat consumption and obesity. We also include a review of well-vetted BC biomarkers related to cytosine-guanine dinucleotides methylation and how they influence BC risk, prognosis, tumour characteristics and response to treatment. LINKED ARTICLES: This article is part of a themed section on The Pharmacology of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.6/issuetoc.

In low rectal cancers without sphincter involvement a permanent stoma can be avoided without compromising oncological safety. Functional outcomes following coloanal anastomosis (CAA) compared to abdominoperineal excision (APR) may be significantly different. This study examines all available comparative quality of life (QoL) data for patients undergoing CAA versus APR for low rectal cancer.Published studies with comparative data on QoL outcomes following CAA versus APR for low rectal cancer were extracted from electronic databases. The study was registered with PROSPERO and adhered to PRISMA (Preferred Reporting Items in Systematic Reviews and Meta-analyses) guidelines. Data was combined using random-effects models.Seven comparative series examined QoL in 527 patients. There was no difference in the numbers receiving neoadjuvant radiotherapy in the APR and CAA groups (OR: 1.19, 95% CI: 0.78-1.81, p = 0.43). CAA was associated with higher mean scores for physical functioning(std mean diff -7.08, 95% CI: -11.92 to -2.25, p = 0.004) and body image (std. mean diff 11.11, 95% CI: 6.04-16.18, p 0.0001). Male sexual problems were significantly increased in patients who had undergone APR compared to CAA (std. mean diff -16.20, 95% CI: -25.76 to -6.64, p = 0.0009). Patients who had an APR reported more fatigue, dyspnoea and appetite loss. Those who had a CAA reported higher scores for both constipation and diarrhoea.It is reasonable to offer a CAA to motivated patients where oncological outcomes will not be threatened. QoL outcomes appear to be superior when intestinal continuity is maintained, and permanent stoma avoided.

Background Female sex has been reported as an independent predictor of severe post-liver transplantation (LT) chronic kidney disease. We performed a by sex post-hoc analysis of the SURF study, that investigated the prevalence of renal impairment following LT, aimed at exploring possible differences between sexes in the prevalence and course of post-LT renal damage. Methods All patients enrolled in the SURF study were considered evaluable for this sex-based analysis, whose primary objective was to evaluate by sex the proportion of patients with estimated Glomerular Filtration Rate (eGFR) 2 at inclusion and follow-up visit. Results Seven hundred thirty-eight patients were included in our analysis, 76% males. The proportion of patients with eGFR 2 was significantly higher in females at initial study visit (33.3 vs 22.8%; p = 0.005), but also before, at time of transplantation (22.9 vs 14.7%; p = 0.0159), as analyzed retrospectively. At follow-up, such proportion increased more in males than in females (33.9 vs 26.0%, p = 0.04). Mean eGFR values decreased over the study in both sexes, with no significant differences. Statistically significant M/F differences in patient distribution by O’Riordan eGFR levels were observed at time of transplant and study initial visit (p = 0.0005 and 0.0299 respectively), but not at follow-up. Conclusions Though the limitation of being performed post-hoc, this analysis suggests potential sex differences in the prevalence of renal impairment before and after LT, encouraging further clinical research to explore such differences more in depth.

Polychlorinated biphenyls (PCB) have been classified by the International Agency for Research on Cancer (IARC) in Group 1 as carcinogenic to human, based on sufficient evidence in humans of an increased risk of cutaneous malignant melanoma and limited evidence for non-Hodgkin lymphoma (NHL). However present findings on the association of PCB exposure and NHL are still controversial. This study examined the relationship between PCB serum levels and risk of NHL in a Northern Italy area (Brescia province), where a chemical factory produced PCBs from 1938 to 1984, causing human contamination. A case–control study of 215 NHL patients and 215 control subjects was conducted. Cases and controls were assayed for serum levels of 33 PCB congeners. No associations were found between risk of NHL and serum levels of total PCBs (OR = 0.51; 95% CI: 0.25–1.04 for highest vs lowest quartile) or specific PCB congeners. The study confirmed a strong association of NHL with HCV infection (OR = 3.60; 95% CI: 1.30–10.02). This case-control study does not support the hypothesis of an association between current serum levels of PCBs and NHL development in the general population.

A significant percentage (~30%) of estrogen receptor-α (ERα)-positive tumors become refractory to endocrine therapies; however, the mechanisms responsible for this resistance remain largely unknown. Chronic exposure to arsenic through foods and contaminated water has been linked to an increased incidence of several tumors and long-term health complications. Preclinical and population studies have indicated that arsenic exposure may interfere with endocrine regulation and increase the risk of breast tumorigenesis. In this study, we examined the effects of sodium arsenite (NaAsIII) exposure in ERα-positive breast cancer cells in vitro and in mammary tumor xenografts. The results revealed that acute (within 4 days) and long-term (10 days to 7 weeks) in vitro exposure to environmentally relevant doses reduced breast cancer 1 (BRCA1) and ERα expression associated with the gain of cyclin D1 (CCND1) and folate receptor 1 (FOLR1), and the loss of methylenetetrahydrofolate reductase (MTHFR) expression. Furthermore, long-term exposure to NaAsIII induced the proliferation and compromised the response of MCF7 cells to tamoxifen (TAM). The in vitro exposure to NaAsIII induced BRCA1 CpG methylation associated with the increased recruitment of DNA methyltransferase 1 (DNMT1) and the loss of RNA polymerase II (PolII) at the BRCA1 gene. Xenografts of NaAsIII-preconditioned MCF7 cells (MCF7NaAsIII) into the mammary fat pads of nude mice produced a larger tumor volume compared to tumors from control MCF7 cells and were more refractory to TAM in association with the reduced expression of BRCA1 and ERα, CpG hypermethylation of estrogen receptor 1 (ESR1) and BRCA1, and the increased expression of FOLR1. These cumulative data support the hypothesis that exposure to AsIII may contribute to reducing the efficacy of endocrine therapy against ERα-positive breast tumors by hampering the expression of ERα and BRCA1 via CpG methylation, respectively of ESR1 and BRCA1.

Background: Faecal immunochemical test (FIT) is emerging as a valid test to rule-out the presence of colorectal cancer (CRC). However, the accuracy of FIT is dependent on the cut-off applied. An additional low-cost test could improve further detection of CRC. Aims: To evaluate the efficacy of combined FIT and volatile organic compounds (VOC) in the detection of CRC within symptomatic populations. Methods: Systematic reviews on the diagnostic accuracy of FIT and VOC, for the detection of CRC, were updated. Meta-analyses were performed adopting a bivariate model for sensitivity and specificity. Clinical utility of combined FIT and VOC was estimated using Fagan's nomogram. Post-test probability of FIT negatives was used as a pre-test probability for VOC. Results: The pooled sensitivity and specificity of FIT at 10µg/g faeces, for the detection of CRC, were 0.914 (95% confidence interval [CI]=0.894-0.936) and 0.783 (CI=0.850-0.696), respectively. For VOC, the sensitivity was 0.837 (CI=0.781-0.881) and the specificity was 0.803 (CI=0.870-0.712). The area under the curve for FIT and VOC were 0.926 and 0.885, respectively. In a population with 5% CRC prevalence, the estimated probability of having CRC following a negative FIT was 0.5% and following both negative FIT and VOC was 0.1%. Conclusions: In a FIT-negative symptomatic population, VOC can be a good test to rule-out the presence of CRC. The estimated probability reduction by 0.4% when both tests being negative offers adequate safety netting in primary care for the exclusion of CRC. The number needed to colonoscope to identify one CRC is eight if either FIT or VOC positive. Cost-effectiveness and clinical accuracy of this approach will need further evaluation.

Crohn’s disease (CD) and ulcerative colitis, two forms of inflammatory bowel disease (IBD), are chronic and relapsing conditions of the gastrointestinal tract both characterized by long lasting chronic inflammation and increased risk of dysplasia and colorectal cancer (CRC). The aim of our study was to evaluate the interobserver agreement about IBD-associated dysplasia among pathologists belonging to the Italian Group for Inflammatory Bowel Diseases (IG-IBD P). The present multicenter survey was performed using telepathology, supported by an open source E-learning platform. Biopsy specimens from 30 colonoscopies and from 20 patients were included. The glass slides of any case, including clinical and endoscopic data, were digitalized and uploaded on the E-learning platform. All the digital slides were grouped in 54 diagnostic “blocks”. Blinded histopathological evaluation on all the digital slides was performed by 20 gastrointestinal pathologists. Closed-ended questions about (1) the occurrence of IBD; (2) the classification of IBD (as UC or CD); (3) the presence of active versus quiescent disease; (4) the presence of dysplasia; (5) the possible association of dysplasia with the sites of disease (dysplasia-associated lesion or mass—DALM vs adenoma-like mass—ALM); (6) the grading of dysplasia according to the ECCO guidelines (negative, indefinite, low grade, high grade categories) and (7) the presence of associated serrated features, were proposed in each case. Inter-observer agreement was evaluated by mean agreement percentage and kappa statistic, when suitable. The diagnosis of IBD was confirmed in 19 of 20 patients, 17 of 19 being classified as UC, 2 as CD. The mean interobserver agreement percentages about (1) the evidence of IBD, (2) the presence of either UC or CD and (3) the activity grading resulted to be 80%, 69% and 86%, respectively. Dysplasia was detected in 8/20 patients, with moderate agreement between pathologists (mean 72%, k 0.48). Particularly, low grade dysplasia was found in 13 biopsies (combined k 0.38), whereas high grade dysplasia in 8 (combined k 0.47). When the endoscopic and histopathological data were combined, features consistent with DALM were found in 6 of 20 patients with low grade dysplasia and those consistent with ALM in 2 patients with low grade dysplasia in a single biopsy (mean agreement: 86%). An associated serrated pattern was discovered in 4 patients (7 biopsies). Our study showed moderate interobserver agreement about the histopathological detection and classification of IBD-associated dysplasia. Further efforts should be undertaken to integrate the histopathological data with both the ancillary tests and molecular investigations.

Background: Surgical treatment of anal fistulas is still a challenge. The aims of this study were to evaluate the adoption and healing rates for the different surgical techniques used in Italy over the past 15 years. Methods: This was a multicenter retrospective observational study of patients affected by simple and complex anal fistulas of cryptoglandular origin who were surgically treated in the period 2003–2017. Surgical techniques were grouped as sphincter-cutting or sphincter-sparing and as technology-assisted or techno-free. All patients included in the study were followed for at least 12 months. Results: A total of 9,536 patients (5,520 simple; 4,016 complex fistulas) entered the study. For simple fistulas, fistulotomy was the most frequently used procedure, although its adoption significantly decreased over the years (P < .0005), with an increase in sphincter-sparing approaches; the overall healing rate in simple fistulas was 81.1%, with a significant difference between sphincter-cutting (91.9%) and sphincter-sparing (65.1%) techniques (P = .001). For complex fistulas, the adoption of sphincter-cutting approaches decreased, while sphincter-sparing techniques were mildly preferred (P < .0005). Moreover, there was a significant trend toward the use of technology-assisted procedures. The overall healing rate for complex fistulas was 69.0%, with a measurable difference between sphincter-cutting (81.1%) and sphincter-sparing (61.4%; P = .001) techniques and between techno-free and technology-assisted techniques (72.5% and 55.0%, respectively; P = .001). Conclusion: Surgical treatment of anal fistulas has changed, with a trend toward the use of sphincter-sparing techniques. The overall cure rate has remained stable, even if the most innovative procedures have achieved a lower success rate.

Background: Soft tissue sarcoma (STS) is a heterogeneous group of rare neoplasms whose aetiology is largely unknown. Dioxin and dioxin-like compounds, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) and polychlorinated biphenyls (PCBs), are potential risk factors for STS. Objectives: To investigate the relation of 17 PCBs congeners, assessed in human plasma, with STS risk. Methods: We conducted a case-control study in Italy, including 52 STS cases and 99 hospital-based controls. Selected PCB were extracted by high-performance liquid chromatography (HPLC) and measured with gas chromatography-mass spectrometry (GC-MS). Odds ratios (OR), and the corresponding 95% confidence intervals (CI), were estimated through multivariate logistic regression models. Results: The most frequently detected PCB congeners were 138, 170, 180 and 149 (detected in 40-77% of controls). The OR for the sum of all 17 PCB congeners was 1.20 (95% CI 0.50-2.92). In categorical analysis no consistent association was found for individual congeners and for groups based on Wolff ’s classification or the degree of chlorination. For continuous estimates, borderline positive associations emerged for Wolff ’s groups 2A (OR 1.23, 95% CI 0.97-1.55), 2B (OR 1.34, 95% CI 1.00-1.77, and 3 (OR 1.19, 95% CI 0.96-1.49), for moderately (OR 1.20, 95% CI 0.96-1.51) and highly (OR 1.18, 95% CI 0.99-1.41) chlorinated PCBs, and for congeners 170 (OR 1.26, 95% CI 0.98-1.63), 180 (OR 1.26, 95% CI 0.97-1.64) and 138 (OR 1.45, 95% CI 1.02-2.04). Discussion: Most associations between PCBs and STS risk were not significant, but, given the limited sample size, we cannot exclude moderate associations.

Postoperative bleeding is a common complication after endoscopic polypectomy, particularly after endoscopic mucosal resection (EMR) of large non-pedunculated polyps, despite prophylactic clipping can reduce its occurrence. Cyanoacrylate glue has recently been proposed as a useful tool in reducing bleeding in surgery because of its adhesive and haemostatic properties. The aim of this study is to evaluate the usefulness of endoscopic application of a modified cyanoacrylate glue in the prevention of early or delayed post EMR bleeding. This is a pilot study. Inclusion criteria were patients between 18 and 75 years old affected by sessile or flat colonic polyps larger than 2 cm. Patients enrolled in the study were randomized in two groups: group A (EMR) and group B (EMR with the application of 0.3 ml of N-butyl-2-cyanoacrylate + methacryloxysulfolane—Glubran 2®). Fifteen patients in both group A and B were enrolled. There were no intraoperative complications but haemostatic clipping was necessary in 3 patients in each group because of active bleeding. Delayed (after 24 h) bleeding occurred in two patients (13.3%) in group A requiring hospital readmission and re-do endoscopy with apposition of haemostatic clips. No case of bleeding was recorded in group B (p = 0.48). The results of this pilot study suggest a potential role of local spray application of Glubran®2 in reducing post-procedural bleeding.

Patient: Male, 40-year-old Final Diagnosis: Gastric perforation Symptoms: Abdominal pain Medication:— Clinical Procedure: Sleeve gastrectomy Nissen fundoplication Specialty: Surgery Objective: Unusual clinical course Background: Laparoscopic sleeve gastrectomy (LSG) has become the most common surgical procedure performed in bariatric surgery. Large hiatal hernias and Barrett’s esophagus are the only contraindications recognized among experts. However, some studies have suggested that LSG may exacerbated gastroesophageal reflux disease (GERD) symptoms or induce postoperative GERD de novo. GERD and erosive esophagitis increase the risk of Barrett’s esophagus. For this reason, in obese patients suffering from GERD, Roux-en-Y gastric bypass is considered the gold standard, or in the case of hiatal hernia, a laparoscopic hiatoplasty should be performed. In order to find some alternative techniques and extend the indication of LSG to obese patient with GERD symptoms, some authors have proposed a single step LSG and Nissen’s fundoplication. Case Report: We report our experience with a male patient who after few months after a single step LSG and Nissen’s fundoplication for morbid obesity and GERD, underwent emergency remnant gastrectomy and esophagojejunostomy because of gastric ischemic perforation. Conclusions: We conclude that, despite being a well-tolerated and feasible surgical procedure, a single step LSG and gastric fundoplication could increase the risk of severe postoperative complications related to LSG, and we believe that, according to guidelines, gastric bypass or LSG with subsequent hiatoplasty should be preferred in obese patients with gastroesophageal reflux symptoms or hiatal hernia.

Laparoscopy for colorectal cancer treatment is widely accepted. However, there is no consensus as to whether or not laparoscopy can be considered the preferred treatment strategy in octogenarian and nonagenarian patients with colon cancer. The aim of this study was to compare operative and postoperative outcomes of laparoscopic right colectomy between oldest-old (≥80 years) and younger (80 years) patients with colon cancer.The study population was sampled from the CLIMHET Study Group cohort. Between January 2005 and December 2015, data were retrieved for all patients who had undergone elective laparoscopic right colectomy for colon cancer in five University Hospital centers in France (CHU of Clermont-Ferrand, Hôpital Civil of Strasbourg-IRCAD, Hôpital Henri-Mondor of Créteil, Hôpital Européen Georges Pompidou of Paris, and CHRU of Tours).Overall, 473 cancer patients were selected and analyzed. There were 156 oldest-old patients (median age: 84.1 years, range: 80-96) and 317 younger patients (median age: 67 years, range: 25-79). After adjusting based on propensity score on gender, obesity, American Society of Anesthesiologists score, smoking, arteriopathy, coronaropathy, comorbidity, and American Joint Committee on Cancer staging, no significant difference was found in operative and postoperative outcomes, except for time to resume a regular diet (3.6 days versus 3.0 days, P = .008) and length of hospital stay (12.1 days versus 9.1 days, P = .03), which were longer for oldest-old patients. Overall and disease-free survival rates were also equivalent between groups.These findings support that laparoscopic right colectomy can be safely performed in cancer patients aged 80 and older, and its outcomes are similar in oldest-old and younger patients.

Breast cancer is the most common type of cancer and leading cause of cancer mortality among women worldwide. However, the majority of breast malignancies are of sporadic etiology. Therefore, identifying risk-mitigating factors may significantly decrease the burden of breast cancer. Diet can have both a predisposing and protective role in breast tumorigenesis. However, establishing efficacy of dietary constituents for cancer prevention has been limited by suboptimal dietary assessment. There is a need to acquire new experimental evidence that can be used to discriminate beneficial from harmful dietary constituents. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that is recognized as the mediator of halogenated and polycyclic aromatic hydrocarbon toxicities. Importantly, evidence points to a breast tumor-promoting role for the AhR. Preclinical and clinical studies suggest that the AhR is overexpressed in advanced and triple negative breast cancers. Several dietary constituents, namely flavonoid compounds, have demonstrated inhibitory effects on AhR activation. Given this background, in this paper we elaborate on the working hypothesis that a diet rich in AhR food agonists favors breast tumor development, whereas a diet rich in AhR food antagonists is protective. As an initial approach to developing an AhR diet hypothesis, we conducted a review of published studies reporting on the association between intake of AhR inhibitory foods and risk of breast cancer. To assist the reader with interpretation of the concepts leading to the AhR diet hypothesis, we have preceded this review with an overview of AhR biology and its role in breast cancer development.

Polychlorinated biphenyls (PCB) have been classified by the International Agency for Research on Cancer (IARC) in Group 1 as carcinogenic to human, based on sufficient evidence in humans of an increased risk of cutaneous malignant melanoma (CMM), however few studies have been done in the general population. This study examined the relationship between PCB plasma levels and risk of CMM adjusting for sun sensitivity and sun exposure in a province of Northern Italy (Brescia), where a chemical factory produced PCBs from 1938 to 1984 causing human contamination. A case–control study of 205 CMM patients and 205 control subjects was conducted. Cases and controls were assayed for plasma levels of 33 PCB congeners. No associations was found between risk of CMM and plasma levels of total PCB (OR = 0.81; 95% CI: 0.34–1.96 for highest vs lowest quartile) or specific congeners. The study confirmed the association with light skin colour (OR = 3.00; 95% CI: 1.91–4.73), cumulative lifetime UV exposure (OR = 2.56; 95% CI: 1.35–4.85) and high level of education (OR = 1.45; 95% CI: 1.03–2.05). This case-control study does not support the hypothesis of an association between current plasma levels of PCBs and CMM development in the general population. Keywords: Melanoma, Polychlorinated biphenyls, Environmental risk factors

Obstructed defecation syndrome (ODS), most commonly found in females, can be treated by a transanal or abdominal approach with good success rate. Nevertheless, patients may experience de novo or persisting pelvic floor dysfunctions after surgery. The aim of this study was to compare the functional outcome of stapled transanal rectal resection (STARR) and ventral rectopexy (VRP) in a series of ODS patients. Forty-nine female patients who had surgery for ODS between 2006 and 2016 were retrospectively evaluated: 28 (median age 60 years, IQR 54–69 years) had VRP and 21 (median age 58 years, IQR 51–66 years) had STARR. ODS was scored with the ODS score while the overall pelvic floor function was assessed with the three axial perineal evaluation (TAPE) score. Quality-of-life was evaluated by the patient assessment of constipation quality-of-life (PAC-Qol) questionnaire administered preoperatively and after 1 year of follow-up. The preoperative median ODS score and TAPE score were comparable in both groups. After a median follow-up of 12 months (range 12–18 months), the median ODS score was 12 (range 10–20) in the STARR group and 9 (range 3–15) in the VRP one (p = 0.02), while the median TAPE score was 70.5 (IQR 60.6–77.3) in the former and 76.8 (IQR 70.2–89.7) in the latter (p = 0.01). Postoperatively the physical domain of the PAC-QoL score had a median value of 2.74 (IQR 1.7–3.75) in the STARR group compared to 1.5 (IQR 1–2.5) in the VRP group (p = 0.03). No major complications were recorded in either group. VRP and STARR can improve defecation in patients with ODS with minimal complications, but the overall pelvic wellness evaluated by the TAPE score improves significantly only after VRP, suggesting a better performance of VRP than STARR when overall pelvic floor function is concerned.

// Aldo Cavallini 1, * , Maria Teresa Rotelli 2, * , Catia Lippolis 1 , Domenico Piscitelli 3 , Rosa Digennaro 2 , Claudia Covelli 3 , Nicola Carella 1 , Matteo Accetturo 4 and Donato Francesco Altomare 2 1 Laboratory of Cellular and Molecular Biology, National Institute for Digestive Diseases, IRCCS “Saverio de Bellis”, Castellana Grotte (BA), Italy 2 General Surgery and Liver Transplantation Unit, Department of Emergency and Organ Transplantation (DETO), University of Bari “Aldo Moro”, Bari, Italy 3 Section of Pathology, Department of Emergency and Organ Transplantation (DETO), University of Bari “Aldo Moro”, Bari, Italy 4 Nephrology Unit, Department of Emergency and Organ Transplantation (DETO), University of Bari “Aldo Moro”, Bari, Italy * These authors contributed equally to this work Correspondence to: Aldo Cavallini, email: cavaldo@libero.it Keywords: desmoid tumor, microRNA, CTNNB1 mutations, tetraspanin3 (TSPAN3) mRNA, serpin family A member 3 (SERPINA3) mRNA Received: November 16, 2016 Accepted: February 22, 2017 Published: March 19, 2017 ABSTRACT Desmoid tumors (DT) are rare, benign, fibroblastic neoplasm with challenging histological diagnosis. DTs can occur sporadically or associated with the familial adenomatous polyposis coli (FAP). Most sporadic DTs are associated with β-catenin gene ( CTNNB1 ) mutations, while mutated APC gene causes FAP disease. microRNAs (miRNAs) are involved in many human carcinogenesis. The miRNA profile was analyzed by microarray in formalin-fixed, paraffin-embedded (FFPE) specimens of 12 patients (8 sporadic, 4 FAP-associated) and 4 healthy controls. One hundred and one mRNAs resulted dysregulated, of which 98 in sporadic DTs and 8 in FAP-associated DTs, 5 were shared by both tumors. Twenty-six miRNAs were then validated by RT-qPCR in 23 sporadic and 7 FAP-associated DT samples matched with healthy controls. The qPCR method was also used to evaluate the CTNNB1 mutational status in sporadic DTs. The correlation between sporadic DTs and miRNA expression showed that miR-21-3p increased in mutated versus wild-type DTs, while miR-197-3p was decreased. The mRNA expression of Tetraspanin3 and Serpin family A member 3, as miR-21-3p targets, and L1 Cell Adhesion Molecule, as miR-197-3p target, was also evaluate. CTNNB1 mutations associated to miRNA dysregulation could affect the genesis and the progression of this disease and help histological diagnosis of sporadic DTs.

The present document contains the recommendations of an expert panel of transplant hepatologists, appointed by the Italian Association for the Study of the Liver (AISF), on how to manage the most common aspects of liver transplantation: the topics covered include: new treatments for HCV in patients on the waiting list for liver transplantation; antiviral treatments in patients with HCV recurrence after liver transplantation; prophylaxis for HBV recurrence after liver transplantation; indications for liver transplantation in alcoholic liver disease; and Immunosuppressive therapy. The statements on each topic were approved by participants at the AISF Transplant Hepatologist Expert Meeting (organized by the Permanent Committee on Liver Transplantation in Mondello on 4–5 October 2015), and are graded according to the Oxford classification of levels of evidence.

New insight into the omic sciences suggests that volatile organic compounds (VOCs) contained in exhaled breath can reflect the healthy or disease state of patients, representing an attractive, promising and non-invasive method of medical investigation. This approach has recently been proposed as a new potential screening tool in colorectal cancer (CRC) patients. However, a possible correlation between the exhaled VOCs and those produced by the cancerous tissue has never been investigated. In this preliminary study, we compare the VOCs exhaled by seven patients affected by CRC with those produce by own cancer tissue and normal colonic mucosa. The VOCs contained in the exhaled breath were sampled with the ReCIVA breath sampler©, while those produced by ex-vivo human tissues weresampled by headspace solid-phase microextraction (HS-SPME) at different incubation times after surgery. In both cases, the collected VOCs were analyzed by Gas Chromatography with Mass Spectrometry (GC-MS). Benzaldehyde, benzene ethyl, benzene methyl, butanoic acid, dodecanoic acid, indole, nonanal, octanoic acid, pentanoic acid, phenol and tetradecane were the VOCs most frequently detected both in the exhaled breath and secreted by tissues. The results showed that cancer tissue and normal colonic mucosa from the same patient produced a similar VOCs pattern but with different fingerprints. In particular, the concentrations of benzaldehyde, benzene ethyl and indole were significantly different in cancer tissue respect the normal colonic mucosa. In conclusion, these preliminary data suggest the involvement of the three compounds in CRC by encouraging further investigation.

Recto-vaginal (RVF) and recto-urethral (RUF) fistulas are infrequent but disabling conditions that severely affect patients’ quality of life. Considering the high recurrence rate after conservative approaches, the best surgical treatment is still challenging. The aim of this study was to evaluate the outcome of graciloplasty to treat patients with complex RVF or RUF, and to investigate its effect on the quality of life. Fourteen patients with RVF and RUF who underwent graciloplasty between 2003 and 2017 were retrospectively enrolled. The main outcome was the healing rate of fistulas. Postoperative patients satisfaction was evaluated administering the Clinical Patient Grading Assessment Scale (CPGAS), SF-36 questionnaires and Changes in Sexual Functioning (CSF) questionnaires. The Wexner score was calculated in case of preoperative faecal incontinence. RVF and RUF were iatrogenic in 11 patients and due to Crohn’s disease in 3 cases. After 1 year of follow-up (IQR 10–14 months), the success rate of the procedure was 78%. Out of three patients with RVF due to Crohn’s disease, two healed after the procedure. Six months after surgery, all eight SF-36 domains significantly improved except for “body pain”; CSF score significantly increased from 35.5 (IQR 31–38.7) to 44 (IQR 37.7–48.5); CPGAS score improved from a median value of 0 (IQR 0–0) to 4 (IQR 3.2–4). The Wexner score was calculated only in 5 patients with preoperative faecal incontinence and it significantly decreased from a median value of 12 (IQR 11–14) to 5 (IQR 4–5). Graciloplasty could be considered as a first option treatment for complex or recurrent RVF and RUF. It shows a good healing rate even in case of unfavourable factors like Crohn’s disease.

Background This manuscript summarizes consensus reached by the International Anorectal Physiology Working Group (IAPWG) for the performance, terminology used, and interpretation of anorectal function testing including anorectal manometry (focused on high‐resolution manometry), the rectal sensory test, and the balloon expulsion test. Based on these measurements, a classification system for disorders of anorectal function is proposed. Methods Twenty‐nine working group members (clinicians/academics in the field of gastroenterology, coloproctology, and gastrointestinal physiology) were invited to six face‐to‐face and three remote meetings to derive consensus between 2014 and 2018. Key recommendations The IAPWG protocol for the performance of anorectal function testing recommends a standardized sequence of maneuvers to test rectoanal reflexes, anal tone and contractility, rectoanal coordination, and rectal sensation. Major findings not seen in healthy controls defined by the classification are as follows: rectoanal areflexia, anal hypotension and hypocontractility, rectal hyposensitivity, and hypersensitivity. Minor and inconclusive findings that can be present in health and require additional information prior to diagnosis include anal hypertension and dyssynergia. Conclusions and Inferences This framework introduces the IAPWG protocol and the London classification for disorders of anorectal function based on objective physiological measurement. The use of a common language to describe results of diagnostic tests, standard operating procedures, and a consensus classification system is designed to bring much‐needed standardization to these techniques., This document summarizes consensus reached by the International Anorectal Physiology Working Group (IAPWG) for the performance of anorectal function testing and introduces a consensus classification for disorders of anorectal function based on objective, physiological measurement.

Laparoscopic liver resection (LLR) is becoming standard practice, replacing the open approach in terms of safety and feasibility. However, few data are available for the elderly. The objective of this study is to assess the feasibility of LLR in elderly patients, by making a comparison with open liver resection (OLR) and with non-elderly patients. Relevant studies found in the Cochrane Library, Embase, PubMed, and Web of Science were used in order to perform a systematic review and meta-analysis. Nine fully extracted comparative studies were included and two groups were identified: Group 1 with a comparison between OLR and LLR in the elderly and Group 2 with a focus on differences after LLR between elderly and non-elderly patients. A total number of 497 elderly patients who underwent LLR were analyzed. A random effect model was used for the meta-analysis. In Group 1, 1025 elderly patients were included: 640 underwent OLR and 385 underwent LLR. LLR was associated with minor blood loss (MD − 240 mL, 95% CI − 416.61, − 63.55; p 0.008; I2 = 96%), less transfusion (8% vs. 13.1%; RR 0.61, 95% CI 0.41, 0.91; p = 0.02; I2 = 0%), fewer postoperative Clavien-Dindo III/IV complications (RR 0.48 in favor of LLR; 95% CI 0.29, 0.77; p = 0.003; I2 = 0%). On the other hand, no significant difference was observed in terms of bile leakage, ascites, mortality, liver failure, or R0 resection. Group 2 included 112 elderly and 276 non-elderly patients who underwent LLR. The meta-analysis showed no significant difference in terms of blood loss, transfusions, liver failure, Clavien-Dindo III/IV complications, postoperative mortality, ascites, bile leak, hospital stay, R0 resection, and operative time. Laparoscopic liver resection is a safe and feasible procedure for elderly patients. However, further randomized studies are required to confirm this.

Background: Evidence on the association between short-term exposure to desert dust and health outcomes is controversial. Objectives: We aimed to estimate the short-term effects of particulate matter ≤ 10 μm (PM10) on mortality and hospital admissions in 13 Southern European cities, distinguishing between PM10 originating from the desert and from other sources. Methods: We identified desert dust advection days in multiple Mediterranean areas for 2001–2010 by combining modeling tools, back-trajectories, and satellite data. For each advection day, we estimated PM10 concentrations originating from desert, and computed PM10 from other sources by difference. We fitted city-specific Poisson regression models to estimate the association between PM from different sources (desert and non-desert) and daily mortality and emergency hospitalizations. Finally, we pooled city-specific results in a random-effects meta-analysis. Results: On average, 15% of days were affected by desert dust at ground level (desert PM10 > 0 μg/m3). Most episodes occurred in spring–summer, with increasing gradient of both frequency and intensity north–south and west–east of the Mediterranean basin. We found significant associations of both PM10 concentrations with mortality. Increases of 10 μg/m3 in non-desert and desert PM10 (lag 0–1 days) were associated with increases in natural mortality of 0.55% (95% CI: 0.24, 0.87%) and 0.65% (95% CI: 0.24, 1.06%), respectively. Similar associations were estimated for cardio-respiratory mortality and hospital admissions. Conclusions: PM10 originating from the desert was positively associated with mortality and hospitalizations in Southern Europe. Policy measures should aim at reducing population exposure to anthropogenic airborne particles even in areas with large contribution from desert dust advections. © 2016, Public Health Services, US Dept of Health and Human Services. All Rights Reserved.

OBJECTIVES: This study aims to evaluate the reliability and clinical utility of NS3 sequencing in hepatitis C virus (HCV) 1-infected patients who were candidates to start a PI-containing regimen. METHODS: NS3 protease sequencing was performed by in-house-developed HCV-1 subtype-specific protocols. Phylogenetic analysis was used to test sequencing reliability and concordance with previous genotype/subtype assignment by commercial genotyping assays. RESULTS: Five hundred and sixty-seven HCV plasma samples with quantifiable HCV-RNA from 326 HCV-infected patients were collected between 2011 and 2014. Overall, the success rate of NS3 sequencing was 88.9%. The success rate between the two subtype protocols (HCV-1a/HCV-1b) was similarly high for samples with HCV-RNA >3 log IU/mL (>92% success rate), while it was slightly lower for HCV-1a samples with HCV-RNA ≤3 log IU/mL compared with HCV-1b samples. Phylogenetic analysis confirmed the genotype/subtype given by commercial genotyping assays in 92.9% (303/326) of cases analysed. In the remaining 23 cases (7.1%), 1 was HCV-1g (previously defined as subtype 1a), 1 was HCV-4d (previously defined as genotype 1b) and 1 was HCV-1b (previously defined as genotype 2a/2c). In the other cases, NS3 sequencing precisely resolved the either previous undetermined/discordant subtype 1 or double genotype/subtype assignment by commercial genotyping assays. Resistance-associated variants (RAVs) to PI were detected in 31.0% of samples. This prevalence changed according to PI experience (17.1% in PI-naive patients versus 79.2% in boceprevir/telaprevir/simeprevir-failing patients). Among 96 patients with available virological outcome following boceprevir/telaprevir treatment, a trend of association between baseline NS3 RAVs and virological failure was observed (particularly for HCV-1a-infected patients: 3/21 failing patients versus 0/22 achieving sustained virological response; P = 0.11). CONCLUSIONS: HCV-NS3 sequencing provides reliable results and at the same time gives two clinically relevant pieces of information: a correct subtype/genotype assignment and the detection of variants that may interfere with the efficacy of PI.

Background & Aims: Despite the excellent efficacy of direct-acting antivirals (DAA) reported in clinical trials, virological failures can occur, often associated with the development of resistance-associated substitutions (RASs). This study aimed to characterize the presence of clinically relevant RASs to all classes in real-life DAA failures. Methods: Of the 200 virological failures that were analyzed in 197 DAA-treated patients, 89 with pegylated-interferon+ribavirin (PegIFN+RBV) and 111 without (HCV-1a/1b/1g/2/3/4=58/83/1/6/24/25; 56.8% treatment experienced; 65.5% cirrhotic) were observed. Sanger sequencing of NS3/NS5A/NS5B was performed by home-made protocols, at failure (N= 200) and whenever possible at baseline (N= 70). Results: The majority of the virological failures were relapsers (57.0%), 22.5% breakthroughs, 20.5% non-responders. RAS prevalence varied according to IFN/RBV use, DAA class, failure type and HCV genotype/subtype. It was 73.0% in IFN group vs 49.5% in IFN free, with the highest prevalence of NS5A-RASs (96.1%), compared to NS3-RASs (75.9% with IFN, 70.5% without) and NS5B-RASs (66.6% with IFN, 20.4% without, in sofosbuvir failures). In the IFN-free group, RASs were higher in breakthrough/non-responders than in relapsers (90.5% vs 40.0%, P= 2 DAA classes showed multiclass resistance, including 11/11 NS3+NS5A failures. Furthermore, 20.0% of patients had baseline-RASs, which were always confirmed at failure. Conclusions: In our failure setting, RAS prevalence was remarkably high in all genes, with a partial exception for NS5B, whose limited resistance is still higher than previously reported. This multiclass resistance advocates for HCV resistance testing at failure, in all three genes for the best second-line therapeutic tailoring.

cope Reduced expression of tumor suppressor genes (TSG) increases the susceptibility to breast cancer. However, only a small percentage of breast tumors is related to family history and mutational inactivation of TSG. Epigenetics refers to non-mutational events that alter gene expression. Endocrine disruptors found in foods and drinking water may disrupt epigenetically hormonal regulation and increase breast cancer risk. This review centers on the working hypothesis that agonists of the aromatic hydrocarbon receptor (AHR), bisphenol A (BPA), and arsenic compounds, induce in TSG epigenetic signatures that mirror those often seen in sporadic breast tumors. Conversely, it is hypothesized that bioactive food components that target epigenetic mechanisms protect against sporadic breast cancer induced by these disruptors. Methods and results This review highlights (i) overlaps between epigenetic signatures placed in TSG by AHR-ligands, BPA, and arsenic with epigenetic alterations associated with sporadic breast tumorigenesis; and (ii) potential opportunities for the prevention of sporadic breast cancer with food components that target the epigenetic machinery. Conclusions Characterizing the overlap between epigenetic signatures elicited in TSG by endocrine disruptors with those observed in sporadic breast tumors may afford new strategies for breast cancer prevention with specific bioactive food components or diet.

Background The farnesoid X receptor (FXR) regulates bile acid (BA) metabolism and possesses tumor suppressor functions. FXR expression is reduced in colorectal tumors of subjects carrying inactivated adenomatous polyposis coli (APC). Identifying the mechanisms responsible for this reduction may offer new molecular targets for colon cancer prevention. Objective We investigated how APC inactivation influences the regulation of FXR expression in colonic mucosal cells. We hypothesized that APC inactivation would epigenetically repress nuclear receptor subfamily 1, group H, member 4 (FXR gene name) expression through increased CpG methylation. Methods Normal proximal colonic mucosa and normal-appearing adjacent colonic mucosa and colon tumors were collected from wild-type C57BL/6J and Apc-deficient (Apc(Min) (/+)) male mice, respectively. The expression of Fxr, ileal bile acid-binding protein (Ibabp), small heterodimer partner (Shp), and cyclooxygenase-2 (Cox-2) were determined by real-time polymerase chain reaction. In both normal and adjacent colonic mucosa and colon tumors, we measured CpG methylation of Fxr in bisulfonated genomic DNA. In vitro, we measured the impact of APC inactivation and deoxycholic acid (DCA) treatment on FXR expression in human colon cancer HCT-116 cells transfected with silencing RNA for APC and HT-29 cells carrying inactivated APC. Results In Apc(Min) (/+) mice, constitutive CpG methylation of the Fxrα3/4 promoter was linked to reduced (60-90%) baseline Fxr, Ibabp, and Shp and increased Cox-2 expression in apparently normal adjacent mucosa and colon tumors. Apc knockdown in HCT-116 cells increased cellular myelocytomatosis (c-MYC) and lowered (∼50%) FXR expression, which was further reduced (∼80%) by DCA. In human HCT-116 but not HT-29 colon cancer cells, DCA induced FXR expression and lowered CpG methylation of FXR. Conclusions We conclude that the loss of APC function favors the silencing of FXR expression through CpG hypermethylation in mouse colonic mucosa and human colon cells, leading to reduced expression of downstream targets (SHP, IBABP) involved in BA homeostasis while increasing the expression of factors (COX-2, c-MYC) that contribute to inflammation and colon cancer.

Patient: Female, 60-year-old Final Diagnosis: Pneumatosis intestinalis Symptoms: Abdominal pain Medication:— Clinical Procedure: — Specialty: Surgery Objective: Rare co-existance of disease or pathology Background: Hepatic portal venous gas (HPVG) associated with pneumatosis intestinalis (PI) can be indicative of several diseases, including inflammatory bowel disease (IBD), infective and obstructive gastrointestinal conditions, and also potentially life-threatening situations such as mesenteric ischemia. Case Report: A 60-year-old female patient came to our attention with evidence at computed tomography (CT) scan of gas in the portal vein and bowel walls with no sign of ischemia. General tenderness of the abdomen with absence of bowel sounds was detected at the physical examination. An exploratory laparotomy was performed with evidence of mesenteric ischemia. Conclusions: Emergency surgery should be indicated when CT signs of PI and HPVG occur along with a clinical situation strongly suggestive of bowel ischemia, even with no radiological sign of this critical condition.

Aim Epidemiological studies have shown that the incidence and mortality rates of colorectal cancer (CRC) vary over 10-fold worldwide where within Westernized societies lower rates are observed amongst populations living within the Mediterranean basin, suggesting a significant influence of environment and dietary style in CRC carcinogenesis. Interpretation of the data concerning the benefits of mediterranean (MD) diet is difficult in vivo because of the variability of alimentary regimens used, the differing compliance with dietary supplementation and because of the non-uniform duration of patient cohort observation. Therefore, the aim of this review is to evaluate the in-vitro effects on colorectal cancer cell lines. Methods the literature concerning the in-vitro effects of 4 of the principal components symbolizing the MD such as olive oil (polyphenol), red chili (capsaicin), tomato (lycopene) and red grapes (resveratrol) have been systematically reviewed. Results Several studies have demonstrated that polyphenols form olive oil, lycopene, resveratrol and capsaicin have multiple anticancer properties affecting several metabolic pathways involved in cancerogenesis, apoptosis, and metastasis in CRC cell lines. Conclusion This review summarizes some of the most recent data potentially supportive of the use of MD in CRC chemoprevention, analyzing the in vitro effects of individual components of the MD on CRC cell development, progression, metastasis and apoptosis.

Several comments immediately following the British vote for Brexit focused on the negative effects both in general terms and in individual sectors, such as that of scientific research. The most feared consequence is the isolation and loss of funding for researchers in community projects. British commentators were later joined by many other European and non-European countries who have interpreted Brexit as a manifestation of impatience with Europe, its constraint and lack of flexibility, topped by an all-English presumption, that they can do better by themselves. This article is protected by copyright. All rights reserved.

Posttranslational modifications of histones, alterations in the recruitment and functions of non-histone proteins, DNA methylation, and changes in expression of noncoding RNAs contribute to current models of epigenetic regulation. Nuclear receptors (NRs) are a group of transcription factors that, through ligand-binding, act as sensors to changes in nutritional, environmental, developmental, pathophysiologic, and endocrine conditions and drive adaptive responses via gene regulation. One mechanism through which NRs direct gene expression is the assembly of transcription complexes with cofactors and coregulators that possess chromatin-modifying properties. Chromatin modifications can be transient or become part of the cellular “memory” and contribute to genomic imprinting. Because many food components bind to NRs, they can ultimately influence transcription of genes associated with biologic processes, such as inflammation, proliferation, apoptosis, and hormonal response, and alter the susceptibility to chronic diseases (e.g., cancer, diabetes, obesity). The objective of this review is to highlight how NRs influence epigenetic regulation and the relevance of dietary compound–NR interactions in human nutrition and for disease prevention and treatment. Identifying gene targets of unliganded and bound NRs may assist in the development of epigenetic maps for food components and dietary patterns. Progress in these areas may lead to the formulation of disease-prevention models based on epigenetic control by individual or associations of food ligands of NRs.

Aim: Abnormalities of one pelvic floor compartment are usually associated with anomalies in the other compartments. Therapies which specifically address one clinical problem may potentially adversely affect other pelvic floor activities. A new comprehensive holistic scoring system defining global pelvic function is presented. Method: A novel scoring system with a software program is presented expressing faecal, urinary and gynaecological functions as a geometric polygon based on symptom-specific questionnaires [the three axial pelvic evaluation (TAPE) score] where differences in overall geometric area vary from normal. After validation in healthy volunteers, its clinical performance was tested on patients with obstructed defaecation, genital prolapse and urinary/faecal incontinence treated by the stapled transanal rectal resection (STARR) procedure, colpo-hysterectomy and sacral nerve modulation, respectively. The TAPE score was correlated with the Pelvic Floor Impact Questionnaire 7 quality of life score. Results: There was good inter-observer variation and internal consistency between two observers recording the TAPE score in normal volunteers. In the STARR patients, constipation improved but the TAPE score was unchanged because of deterioration in other pelvic floor functions leading to an unchanged overall postoperative recorded quality of life. Conversely, incontinent patients treated with sacral nerve stimulation improved their function showing concomitant improvements in TAPE scores and quality of life indices. Similar correlative improvements were noted in patients undergoing hysterectomy for genital prolapse. Conclusion: The TAPE score defines the impact of symptom-specific treatments on the pelvic floor and may provide an opportunity for comparison of clinical data between units and in clinical trials of specific medical and surgical pelvic floor management. (Less)

Patients with gallstones are often affected by alimentary disorders contributing to the onset of gallstones disease. Cholecystectomy can have nutritional and metabolic consequences in the short-term (diarrhea, abdominal pain and bloating) and in the long-term (increased Body Mass Index with metabolic syndrome, gastritis, liposoluble vitamin deficiency). Pathogenic mechanisms behind these disturbances are reviewed and the need for an early post-operative nutritional intervention based on low-lipid, high-fibers diet, is highlighted.

To further characterize the genetic basis of primary biliary cirrhosis (PBC), we genotyped 2426 PBC patients and 5731 unaffected controls from three independent cohorts using a single nucleotide polymorphism (SNP) array (Immunochip) enriched for autoimmune disease risk loci. Meta-analysis of the genotype data sets identified a novel disease-associated locus near the TNFSF11 gene at 13q14, provided evidence for association at six additional immune-related loci not previously implicated in PBC and confirmed associations at 19 of 22 established risk loci. Results of conditional analyses also provided evidence for multiple independent association signals at four risk loci, with haplotype analyses suggesting independent SNP effects at the 2q32 and 16p13 loci, but complex haplotype driven effects at the 3q25 and 6p21 loci. By imputing classical HLA alleles from this data set, four class II alleles independently contributing to the association signal from this region were identified. Imputation of genotypes at the non-HLA loci also provided additional associations, but none with stronger effects than the genotyped variants. An epistatic interaction between the IL12RB2 risk locus at 1p31and the IRF5 risk locus at 7q32 was also identified and suggests a complementary effect of these loci in predisposing to disease. These data expand the repertoire of genes with potential roles in PBC pathogenesis that need to be explored by follow-up biological studies.

Susceptibility to primary biliary cirrhosis (PBC) is strongly associated with human leukocyte antigen (HLA)-region polymorphisms. To determine if associations can be explained by classical HLA determinants, we studied Italian, 676 cases and 1440 controls, genotyped with dense single-nucleotide polymorphisms (SNPs) for which classical HLA alleles and amino acids were imputed. Although previous genome-wide association studies and our results show stronger SNP associations near DQB1, we demonstrate that the HLA signals can be attributed to classical DRB1 and DPB1 genes. Strong support for the predominant role of DRB1 is provided by our conditional analyses. We also demonstrate an independent association of DPB1. Specific HLA-DRB1 genes (*08, *11 and *14) account for most of the DRB1 association signal. Consistent with previous studies, DRB1*08 (P=1.59 × 10(-11)) was the strongest predisposing allele, whereas DRB1*11 (P=1.42 × 10(-10)) was protective. Additionally, DRB1*14 and the DPB1 association (DPB1*03:01; P=9.18 × 10(-7)) were predisposing risk alleles. No signal was observed in the HLA class 1 or class 3 regions. These findings better define the association of PBC with HLA and specifically support the role of classical HLA-DRB1 and DPB1 genes and alleles in susceptibility to PBC.Genes and Immunity advance online publication, 10 May 2012; doi:10.1038/gene.2012.17.

AIM Sacral nerve stimulation is an effective treatment for urinary and faecal incontinence even though its mechanism of action is uncertain. Central nervous system involvement by 'setting-up' neurological mechanisms appointed to control pelvic function has been hypothesized. The study aimed to evaluate whether the effects of long-term sacral nerve stimulation are memorized and therefore maintained after switching off the stimulator. METHOD Patients having sacral nerve stimulation for faecal and/or urinary incontinence for at least 1 year had the stimulator turned off and the results monitored. Data recorded with the stimulator off were compared with post-implant data. If symptoms recurred the stimulator was switched back on. Nineteen patients entered the study. Fourteen had faecal and/or urinary incontinence and five had faecal incontinence alone. The symptoms were assessed by means of a bowel function diary and dedicated questionnaire. RESULTS In 10 patients symptoms recurred at different intervals after a median off period of 3.4 months with a probability of symptom relapse of 55%. The Fecal Incontinence Quality of Life (FIQL) score did not show any significant difference in nine patients with the stimulator off for at least 1 year. No factors predictive of symptom recurrence were identified although an idiopathic aetiology, severity of disease and urinary incontinence had higher hazard ratios. During the off period, none of the scores and episodes of incontinence showed significant changes compared with the on period. CONCLUSION The effects of sacral nerve stimulation on faecal and urinary incontinence were maintained in about half of patients after switching the stimulator off, but in some symptoms returned after different periods of time. The data shed new light on possible effects of sacral nerve stimulation on brain neuroplasticity in the control of continence.

The management of haemorrhoids has evolved rapidly during the past few decades. Several new treatments have been proposed with the aim of reducing patients' postoperative pain, time to return to normal life, risk of early and late complications, and recurrence rate. Although conservative treatment based on dietary and lifestyle changes can help the majority of patients, and rubber band ligation and phlebotonic drugs can effectively treat grade I and II haemorrhoids, surgery is required for the most advanced stages. Milligan-Morgan haemorrhoidectomy is considered to be the gold-standard approach for grade IV haemorrhoids. An increasing number of minimally invasive treatment options, including mucopexy with or without mucosal resection and haemorrhoid artery ligation, have now been proposed for the management of grade III haemorrhoids. These approaches aim to correct the underlying pathophysiological mechanisms involved in the aetiology of haemorrhoids. An increased risk of recurrence is the price to pay for these minimally invasive and less painful treatments, but the sparing of the sensitive anoderm and a rapid return to normal life without pain are greatly appreciated by patients. An algorithm for the management of haemorrhoids using evidence-based medicine is also presented here.

It is increasingly clear that a tailored therapeutic approach to patients with hepatitis C virus infection is needed. Success rates in difficult to treat and low-responsive hepatitis C virus patients are not completely satisfactory, and there is the need to optimise treatment duration and intensity in patients with the highest likelihood of response. In addition, the management of special patient categories originally excluded from phase III registration trials needs to be critically re-evaluated. This article reports the recommendations for the treatment of hepatitis C virus infection on an individual basis, drafted by experts of three scientific societies.

Background: Immigrants represent a good epidemiological model to evaluate the relative influence of environmental and inherited factors on the development of allergy. Several studies on allergy in adults have been published, but few data in children are available. We aimed to investigate the differences, between Italian and immigrant children, in clinical characteristics of respiratory allergy. Methods: This was a multicentre cross-sectional study involving children born in Italy from Italian parents and children born either in Italy or abroad from immigrants. Children referred firstly for allergic respiratory disease (rhinitis/asthma), with an ascertained clinical diagnosis and IgE sensitization to inhalants, were included. Demographic features, comorbidities, severity of disease, and sensitization profile were compared between Italians and immigrants, separating also those born in Italy from immigrant parents and those born abroad. Results: One hundred and sixty-five immigrant allergic children were enrolled (100 male, mean age 8.3 yr), 128 of whose had both parents immigrated. Italian children were 237 (156 male, mean age 8.4 yr). The Italian and immigrant children were similar, apart from pet's ownership and family size. There was no difference in the severity of rhinitis/asthma between the groups, whereas significant differences were found in the pattern of sensitization: immigrant children were more frequently sensitized to house dust mites (73.3% vs. 51%, respectively; p = 0.002) and less to grass (41.8% vs. 57.8%; p = 0.002); this was retained also in monosensitized children. Immigrant children born in Italy (n = 105) had a lower prevalence of rhinitis vs. Italians (68.3% vs. 87.6%, respectively, p = 0.003) and of sensitization to grass (28.3% vs. 49.5%, respectively, p = 0.008). No difference was found among macro-regions of origin and demographic or clinical features. Conclusions: Immigrant children born either in Italy or abroad did not show significant differences in the clinical pattern of the respiratory allergic disease when compared to children born from Italian parents. © 2014 John Wiley & Sons A/S.

Introduction Genotoxic biomarkers have been studied largely in adult population, but few studies so far have investigated them in children exposed to air pollution. Children are a high-risk group as regards the health effects of air pollution and some studies suggest that early exposure during childhood can play an important role in the development of chronic diseases in adulthood. The objective of the project is to evaluate the associations between the concentration of urban air pollutants and biomarkers of early biological effect in children, and to propose a model for estimating the global risk of early biological effects due to air pollutants and other factors in children. Methods and analysis Two biomarkers of early biological effects, DNA damage by the comet assay and the micronuclei (MN) test, will be investigated in oral mucosa cells of 6–8-year-old children. Concurrently, some toxic airborne pollutants (polycyclic aromatic hydrocarbon (PAH) and nitro-PAH) and in vitro air mutagenicity and toxicity in ultra-fine air particulates (PM0.5) will be evaluated. Furthermore, demographic and socioeconomic variables, other sources of exposures to air pollutants and lifestyle variables will be assessed by a structured questionnaire. The associations between sociodemographic, environmental and other exposure variables and biomarkers of early biological effect using univariate and multivariate models will be analysed. A tentative model for calculating the global absolute risk of having early biological effects caused by air pollution and other variables will be proposed. Ethics and dissemination The project has been approved by the Ethics Committees of the local Health Authorities. The results will be communicated to local Public Health Agencies, for supporting educational programmes and health policy strategies. LIFE+2012 Environment Policy and Governance. LIFE12 ENV/IT/000614.

Objectives: We studied survival and associated risk factors in an Italian nationwide cohort of HIV-infected individuals after an AIDS-defining cancer (ADC) or non-AIDS-defining cancer (NADC) diagnosis in the modern cART era. Methods: Multi-center, retrospective, observational study of HIV patients included in the MASTER Italian Cohort with a cancer diagnosis from January 1998 to September 2012. Malignancies were divided into ADC or NADC on the basis of the Centre for Disease Control-1993 classification. Recurrence of cancer and metastases were excluded. Survivals were estimated according to the Kaplan-Meier method and compared according to the log-rank test. Statistically significant variables at univariate analysis were entered in a multivariate Cox regression model. Results: Eight hundred and sixty-six cancer diagnoses were recorded among 13,388 subjects in the MASTER Database after 1998: 435 (51%) were ADCs and 431 (49%) were NADCs. Survival was more favorable after an ADC diagnosis than a NADC diagnosis (10-year survival: 62.7%±2.9% vs. 46%±4.2%; p = 0.017). Non-Hodgkin lymphoma had lower survival rates than patients with Kaposi sarcoma or cervical cancer (10-year survival: 48.2%±4.3% vs. 72.8%±4.0% vs. 78.5%±9.9%; p

Epigenetic mechanisms may contribute to reduced expression of the tumor suppressor gene BRCA-1 in sporadic breast cancers. Through environmental exposure and diet, humans are exposed to xenobiotics and food compounds that bind the aromatic hydrocarbon receptor (AhR). AhR-ligands include the dioxin-like and tumor promoter 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD). The activated AhR regulates transcription through binding to xenobiotic response elements (XREs=GCGTG) and interactions with transcription cofactors. Previously, we reported on the presence of several XREs in the proximal BRCA-1 promoter and that the expression of endogenous AhR was required for silencing of BRCA-1 expression by TCDD. Here, we document that in estrogen receptor-α-positive and BRCA-1 wild-type MCF-7 breast cancer cells, the treatment with TCDD attenuated 17β-estradiol-dependent stimulation of BRCA-1 protein and induced hypermethylation of a CpG island spanning the BRCA-1 transcriptional start site of exon-1a. Additionally, we found that TCDD enhanced the association of the AhR; DNA methyl transferase (DNMT)1, DNMT3a and DNMT3b; methyl binding protein (MBD)2; and trimethylated H3K9 (H3K9me3) with the BRCA-1 promoter. Conversely, the phytoalexin resveratrol, selected as a prototype dietary AhR antagonist, antagonized at physiologically relevant doses (1 μmol/L) the TCDD-induced repression of BRCA-1 protein, BRCA-1 promoter methylation and the recruitment of the AhR, MBD2, H3K9me3 and DNMTs (1, 3a and 3b). Taken together, these observations provide mechanistic evidence for AhR agonists in the establishment of BRCA-1 promoter hypermethylation and the basis for the development of prevention strategies based on AhR antagonists.