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Introduction: Single or double prolapsed pile instead of full muco-hemorrhoidal prolapse is a common finding in patients with symptomatic III or IV degree hemorrhoids. For this selected group of patients, relief of symptoms could be achieved by managing the single/double prolapsed piles instead of performing traditional hemorrhoidectomy. The aim of this single-center study was to evaluate the safety and medium- and long-term effectiveness of an outpatient tailored Milligan-Morgan hemorrhoidectomy (MMH) performed under local anesthesia (LA).Material and methods: Clinical records of 202 patients submitted to outpatient tailored MMH, under LA and without anal dilation, treated between 2013 and 2020, were retrospectively reviewed using a prospectively maintained database and completed by a telephone interview or outpatient consultation. Postoperative pain score, the need for painkillers, postoperative complications and symptoms recurrence, return to working activities, and patient grading assessment scale were recorded.Results: Thirty-five (17%) out of 202 patients recruited were lost to the follow-up. One hundred and fifty-two and 15 patients underwent a single and double pile hemorrhoidectomy, respectively. With regard to postoperative outcomes, visual analogue scale (VAS) decreased from a median value of 4 [interquartile range (IQR) 2–6] on the day of surgery to 1 (IQR 0–4) on the 10th postoperative day (p < 0.001). Sixty-one patients (37%) needed oral painkillers during the 1st week after surgery. There was no mortality or major postoperative complication. Bleeding requiring hospital readmission was reported in seven (4%) patients, and one patient underwent emergency surgery with no need for blood transfusion. No postoperative urinary retention, anal incontinence, or stricture occurred in the series. During the median follow-up of 39 (IQR 12–60) months, 26 patients (16%) reported symptoms of recurrence but only six underwent traditional MMH. Recovery to normal activity occurred within a median period of 6 days (IQR 3–10) and the Clinical Patient Grading Assessment Scale (CPGAS) at 1 year after surgery was reported to be a “good deal better.”Conclusions: Tailored MMH performed under LA in an ambulatory setting can be considered a safe and effective technique with high compliance and satisfaction of patients.

Background: Concerns are emerging that a high-fat diet rich in n-6 PUFA (n-6HFD) may alter gut microbiome and increase the risk of intestinal disorders. Research is needed to model the relationships between consumption of an n-6HFD starting at weaning and development of gut dysbiosis and colonic inflammation in adulthood. We used a C57BL/6J mouse model to compare the effects of exposure to a typical American Western diet (WD) providing 58.4%, 27.8%, and 13.7% energy (%E) from carbohydrates, fat, and protein, respectively, with those of an isocaloric and isoproteic soybean oil-rich n-6HFD providing 50%E and 35.9%E from total fat and carbohydrates, respectively on gut inflammation and microbiome profile. Methods: At weaning, male offspring were assigned to either the WD or n-6HFD through 10–16 weeks of age. The WD included fat exclusively from palm oil whereas the n-6HFD contained fat exclusively from soybean oil. We recorded changes in body weight, cyclooxygenase-2 (COX-2) expression, colon histopathology, and gut microbiome profile. Results: Compared to the WD, the n-6HFD increased plasma levels of n-6 fatty acids, colonic expression of COX-2, and the number of colonic inflammatory and hyperplastic lesions. At 16 weeks of age, the n-6HFD caused a marked reduction in the gut presence of Firmicutes, Clostridia, and Lachnospiraceae, and induced growth of Bacteroidetes and Deferribacteraceae. At the species level, the n-6HFD sustains the gut growth of proinflammatory Mucispirillum schaedleri and Lactobacillus murinus. Conclusions: An n-6HFD consumed from weaning to adulthood induces a shift in gut bacterial profile associated with colonic inflammation.

Simple Summary Emerging evidence has suggested that cancer-derived extracellular vesicles (EVs) have a crucial role in mediating directional metastasis to the peritoneal surface in colorectal cancer (CRC). We investigated the EV-mediated crosstalk between tumor and mesothelial cells which may drive remodeling of the premetastatic niche to allow tumor spread to the peritoneal surface. Our findings demonstrated that cancer-derived EVs triggered apoptosis and reduced mesothelial cell invasiveness and mesothelial-to-mesenchymal transition. On the other hand, mesothelial cells actively supported tumor invasion by releasing EVs, which induced upregulation of the major pro-invasive system in tumor cells. For the first time, we provide evidence of EV-driven mechanisms of CRC progression in patient-derived models, highlighting the crucial role of EVs in the reprogramming of mesothelial and tumor cells to establish the metastatic process. Abstract Advanced colorectal cancer (CRC) is highly metastatic and often results in peritoneal dissemination. The extracellular vesicles (EVs) released by cancer cells in the microenvironment are important mediators of tumor metastasis. We investigated the contribution of EV-mediated interaction between peritoneal mesothelial cells (MCs) and CRC cells in generating a pro-metastatic environment in the peritoneal cavity. Peritoneal MCs isolated from peritoneal lavage fluids displayed high CD44 expression, substantial mesothelial-to-mesenchymal transition (MMT) and released EVs that both directed tumor invasion and caused reprogramming of secretory profiles by increasing TGF-β1 and uPA/uPAR expression and MMP-2/9 activation in tumor cells. Notably, the EVs released by tumor cells induced apoptosis by activating caspase-3, peritoneal MC senescence, and MMT, thereby augmenting the tumor-promoting potential of these cells in the peritoneal cavity. By using pantoprazole, we reduced the biogenesis of EVs and their pro-tumor functions. In conclusion, our findings provided evidence of underlying mechanisms of CRC dissemination driven by the interaction of peritoneal MCs and tumor cells via the EVs released in the peritoneal cavity, which may have important implications for the clinical management of patients.

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.

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.

A conference abstract from NIRItalia online 2021 in English and Italian.

Trop-2 is a type I transmembrane glycoprotein, which is overexpressed in the majority of carcinomas, where it drives tumor cell proliferation. In its mature, glycosylated/functionally-competent form, Trop-2 associates with worse prognosis. A global quest was conducted for identifying decisive drivers of cancer metastasis. Cancer cell spheroids, wound healing and cell aggregation assays were utilized to assess cell-cell adhesion capacity. Immunofluorescence confocal microscopy and flow cytometry analysis were utilized to quantify expression of target signaling proteins, IHC analysis quantified the expression of target molecules in primary tumors and metastases. Pre-clinical models of orthotopic growth of colon cancer and metastatic diffusion to the liver were utilized. Xenotransplant transcriptome profiling analyzed transcription of EMT-related determinants. This led us to identify Trop-2 as a unique upregulated gene in colon cancer metastasis. Trop-2 was here shown to bind highly-expressed E-cadherin at the cell membrane. Trop-2 binding released E-cadherin from the cytoskeleton, inhibited cell-cell adhesion functions and activated signaling through β-catenin. This occurred in the absence of transcriptional downregulation of the CDH1 gene by EMT-associated transcription factors. The Trop-2/E-cadherin/β-catenin program was shown to lead to anti-apoptotic signaling, increased cell migration and enhanced cancer cell survival. In an orthotopic model of colon cancer, Trop-2 caused metastatic diffusion to the liver. The Trop-2-led E-cadherin-inactivation metastasis program was then found to induce metastatic relapse and shorter overall survival of colon cancer patients. Corresponding impact was indicated on breast, colon, ovary, uterus, stomach cancer metastatic diffusion, for broad impact on metastatic diffusion in human cancer. Acknowledgments:Support was provided by grants of Italian Ministry of Development (MI01_00424) and of University and Research (SCN_00558). M.T. was supported by the Programma Per Giovani Ricercatori “Rita Levi Montalcini” (Grant PGR12I7N1Z). Citation Format: Saverio Alberti, Emanuela Guerra, Valeria Relli, Rossano Lattanzio, Martina Ceci, Khouloud Boujnah, Valeria Garbo, Antonino Moschella, donato F. Altomare, Raffaella Depalo, Marco Trerotola. Trop-2 inactivates E-cadherin for metastatic diffusion in the absence of EMT [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2851.

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.

The HAWC Collaboration has reported the detection of an extended $\gamma$-ray emission around the Geminga and Monogem pulsars of a few degree extension. Very recently, the LHAASO Collaboration released also the data for an extended $\gamma$-ray emission around the pulsar PSR J0622+3749. This flux can be explained with electrons and positrons injected from these sources and their inverse Compton Scattering on the interstellar radiation fields. So far the size of such $\gamma-$ray halos has been interpreted as the result of the diffusion coefficient around the sources being about two orders of magnitude smaller than the average in the Galaxy. However, this conclusion is driven by the assumption that particles propagate diffusively right away after the injection without taking into account the ballistic propagation. The propagation of cosmic-ray leptons in the proximity of the Geminga, Monogem and PSR J0622+3749 pulsars is examined here considering the transition from the quasi-ballistic, valid for the most recently injected particles, to the diffusive transport regime. For typical interstellar values of the diffusion coefficient, the quasi-ballistic regime dominates the lepton distribution up to distances of a few tens of parsec from the pulsar for particle energies above $\sim 10$ TeV. In this regime the resulting $\gamma-$ray source tends to be rather compact, despite particles travel a long distance. Indeed, for larger values of the diffusion coefficient, particles propagate ballistically up to larger distances with the result of a more point-like $\gamma-$ray source. When such transition is taken into account, a good fit to the HAWC and LHAASO $\gamma-$ray data around Geminga, Monogem and PSR J0622+3749 is obtained without the need to invoke a strong suppression of the diffusion coefficient., Comment: 10 pages, 4 figures. This version includes other two sources (Monogem and PSR J0622+3749) with respect to the first version

Background: In randomized controlled trials, add-on brivaracetam (BRV) reduced seizure frequency in patients with drug-resistant focal epilepsy. Studies performed in a naturalistic setting are a useful complement to characterize the drug profile. Objective: This multicentre study assessed the effectiveness and tolerability of adjunctive BRV in a large population of patients with focal epilepsy in the context of real-world clinical practice. Methods: The BRIVAFIRST (BRIVAracetam add-on First Italian netwoRk STudy) was a retrospective, multicentre study including adult patients prescribed adjunctive BRV. Patients with focal epilepsy and 12-month follow-up were considered. Main outcomes included the rates of seizure‐freedom, seizure response (≥50% reduction in baseline seizure frequency), and treatment discontinuation. The incidence of adverse events (AEs) was also considered. Analyses by levetiracetam (LEV) status and concomitant use of strong enzyme-inducing antiseizure medications (EiASMs) and sodium channel blockers (SCBs) were performed. Results: A total of 1029 patients with a median age of 45years (33–56) was included. At 12 months, 169 (16.4%) patients were seizure-free and 383 (37.2%) were seizure responders. The rate of seizure freedom was 22.3% in LEV-naive patients, 7.1% in patients with prior LEV use and discontinuation due to insufficient efficacy, and 31.2% in patients with prior LEV use and discontinuation due to AEs (p&nbsp

International audience; The detection of an extended multi-TeV gamma ray emission around the Geminga and Monogempulsars by the HAWC collaboration provides a unique tool to investigate the transport properties ofcosmic rays in the turbulent magnetized interstellar medium. Previous analyses of such emissionin the framework of pure isotropic diffusion lead to infer a suppression of the diffusion coefficientin the pulsars region by at least two orders of magnitude compared to typical values found inmodels of Galactic cosmic ray propagation. In this work, we investigate the transition from theballistic to the diffusive regime, and show that, when such transition is taken into account, a goodfit to the HAWC γ−ray data around Geminga and Monogem is obtained with typical values of theinterstellar diffusion coefficient.

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.

A diet high in n-6 polyunsaturated fatty acids (PUFAs) may contribute to inflammation and tissue damage associated with obesity and pathologies of the colon and liver. One contributing factor may be dysregulation by n-6 fatty acids of enterohepatic bile acid (BA) metabolism. The farnesoid X receptor (FXR) is a nuclear receptor that regulates BA homeostasis in the liver and intestine. This study aims to compare the effects on FXR regulation and BA metabolism of a palm oil-based diet providing 28% energy (28%E) from fat and low n-6 linoleic acid (LA, 2.5%E) (CNTL) with those of a soybean oil-based diet providing 50%E from fat and high (28%E) in LA (n-6HFD). Wild-type (WT) littermates and a transgenic mouse line overexpressing the Fxr&alpha, 1 isoform under the control of the intestine-specific Villin promoter (Fxr&alpha, 1TG) were fed the CNTL or n-6HFD starting at weaning through 16 weeks of age. Compared to the CNTL diet, the n-6HFD supports higher weight gain in both WT and Fxr&alpha, TG littermates, increases the expression of Fxr&alpha, 1/2, and peroxisome proliferator-activated receptor-&gamma, 1 (Ppar&gamma, 1) in the small intestine, Fxr&alpha, 1/2 in the colon, and cytochrome P4507A1 (Cyp7a1) and small heterodimer protein (Shp) in the liver, and augments the levels of total BA in the liver, and primary chenodeoxycholic (CDCA), cholic (CA), and &beta, muricholic (&beta, MCA) acid in the cecum. Intestinal overexpression of the Fxra1TG augments expression of Shp and ileal bile acid-binding protein (Ibabp) in the small intestine and Ibabp in the proximal colon. Conversely, it antagonizes n-6HFD-dependent accumulation of intestinal and hepatic CDCA and CA, hepatic levels of Cyp7a1, and expression of Ppar&gamma, in the small intestine. We conclude that intestinal Fxr&alpha, 1 overexpression represses hepatic de novo BA synthesis and protects against n-6HFD-induced accumulation of human-specific primary bile acids in the cecum.

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.

A diet high in n-6 polyunsaturated fatty acids (PUFAs) may contribute to inflammation and tissue damage associated with obesity and pathologies of the colon and liver. One contributing factor may be dysregulation by n-6 fatty acids of enterohepatic bile acid (BA) metabolism. The farnesoid X receptor (FXR) is a nuclear receptor that regulates BA homeostasis in the liver and intestine. This study aims to compare the effects on FXR regulation and BA metabolism of a palm oil-based diet providing 28% energy (28%E) from fat and low n-6 linoleic acid (LA, 2.5%E) (CNTL) with those of a soybean oil-based diet providing 50%E from fat and high (28%E) in LA (n-6HFD). Wild-type (WT) littermates and a transgenic mouse line overexpressing the Fxrα1 isoform under the control of the intestine-specific Villin promoter (Fxrα1TG) were fed the CNTL or n-6HFD starting at weaning through 16 weeks of age. Compared to the CNTL diet, the n-6HFD supports higher weight gain in both WT and FxrαTG littermates; increases the expression of Fxrα1/2, and peroxisome proliferator-activated receptor-γ1 (Pparγ1) in the small intestine, Fxrα1/2 in the colon, and cytochrome P4507A1 (Cyp7a1) and small heterodimer protein (Shp) in the liver; and augments the levels of total BA in the liver, and primary chenodeoxycholic (CDCA), cholic (CA), and β-muricholic (βMCA) acid in the cecum. Intestinal overexpression of the Fxra1TG augments expression of Shp and ileal bile acid-binding protein (Ibabp) in the small intestine and Ibabp in the proximal colon. Conversely, it antagonizes n-6HFD-dependent accumulation of intestinal and hepatic CDCA and CA; hepatic levels of Cyp7a1; and expression of Pparγ in the small intestine. We conclude that intestinal Fxrα1 overexpression represses hepatic de novo BA synthesis and protects against n-6HFD-induced accumulation of human-specific primary bile acids in the cecum.

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.

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.