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Perianal fistulizing Crohn's disease (PFCD) is a common, disabling and aggressive phenotype that negatively impacts on the quality of life of affected patients. Its successful treatment is still a struggle for both physicians and patients. Significant advances in the management of this condition have occurred in the last two decades holding promise for a better future. This culminated into the concept of a collaborative multidisciplinary approach using the latest medical therapies combined with modern surgical and endoscopic techniques. Despite this, PFCD management and treatment have not been standardized yet. Thus the gastroenterologist and surgeon have to be familiar with several approaches and/or techniques. The positioning of each therapeutic option will certainly evolve with new data, but for the time being it should be driven by patient's characteristics, physician's preference and/or experience, costs and availability in local practice. Additionally, patient's perception of benefits and risks of treatment may differ from those of physicians and recognition of this difference is a starting point for difficult clinical decision-making. In this paper, a multidisciplinary group of Italian IBD experts explore and discuss current medical and surgical therapeutic options, highlighting areas of unmet needs in PFCD, with particular focus on the optimal patient flow within the Italian clinical reality.

The Italian Society of Colorectal Surgery (SICCR) promoted the project reported here, which consists of a Position State‑ ment of Italian colorectal surgeons to address the surgical aspects of ulcerative colitis management. Members of the society were invited to express their opinions on several items proposed by the writing committee, based on evidence available in the literature. The results are presented, focusing on relevant points. The present paper is not an alternative to available guidelines; rather, it ofers a snapshot of the attitudes of SICCR surgeons about the surgical treatment of ulcerative colitis. The committee was able to identify some points of major disagreement and suggested strategies to improve the quality of available data and acceptance of guidelines.

The spread of COVID-19 pandemic forced the national healthcare system to reorganize almost all surgical services, in order to maintain an adequate therapeutic offer. At General Surgery department of Fondazione Policlinico Gemelli in Rome, surgical procedures were progressively reduced to provide beds and personnel for COVID-19. The aim of our study was to analyze the effect of one year of COVID-19 pandemic on Inflammatory Bowel Disease (IBD) surgery in a cohort of patients and evaluate post-operative short-term complications.Our team retrospectively analyzed the records of IBD patients who were referred to an IBD-related resective surgery from January 2020 to December 2020. These patients were compared to a comparable group of IBD patients who were operated from January 2019 to December 2019.A total of 160 patients were included in the study. Median age was 44 (range 15-77). Patients were referred for Ulcerative colitis (23.1%) and Crohn's disease (76.9%). Eighty-three patients underwent surgery from January 2020 to December 2020, which constitutes a 4.6% increase in the number of patients compared to the same period in 2019. Median post-operative hospital stay increased (7 days in 2019 vs. 6 days in 2020). Laparoscopic was the most frequently performed procedure during both periods (49% in 2019 and 59% in 2020). Complication rates, reported as Clavien-Dindo score 3 or 4, slightly decreased in 2020 (6.5 in 2019 vs. 4.8 in 2020). PCR test for detection of COVID-19 infection was conducted in all the patients before the hospitalization. Two patients out of 70 were tested positive for COVID-19 and their surgeries were rescheduled.There was no significant reduction in IBD resective surgeries at our center in 2020, nor a deterioration of the outcomes. A reduction of other elective surgical procedures had to be carried out and adequate protective measures for both patients and healthcare workers were established.

Aim To present characteristics of collecting autologous peripheral blood stem cells over a one-year period with an emphasis on efficiency and safety. Methods A retrograde analysis of 24 leukapheresis in 20 adult patients with malignant haematological diseases in the Blood Transfusion Institute of the Federation of Bosnia and Herzegovina in Sarajevo, was done. Cell separators Amicus and Spectra Optia were used for collection procedures. Results The patient's age ranged from 27 to 65 years. Target cells were collected in one procedure in sixteen patients, while in four patients they were collected in two procedures. The mean CD34+ collection efficiency was 57.7%. The median number of CD34+ cells and percentage of CD34+ cells in the products were 5.52x10e6/kg (range 3.28-9.00) and 1.57% (range 0.96-2.91). A strong positive correlation was found between the number of CD34+ cells in peripheral blood on the apheresis day and the amount of CD34+ cells collected in the products (rs =0.73). A total of 95% of patients collected the amount of ≥3x10e6/kg and 55% of ≥5x10e6/kg CD34+ cells for a single transplant. A decrease in platelet count, haemoglobin and haematocrit values after the procedure was not significant. Potassium decrease showed statistical significance (p0.000). Adverse events occurred during one procedure (4.2%). Conclusion A low number of adverse events and good collection efficiency with adequate patient monitoring, indicate that leukapheresis is a safe procedure that is successfully used in the autologous transplantation process in the treatment of malignant haematological diseases.

Patients with Crohn's disease experience an increased risk of postoperative complications and disease recurrence. The aim of this study was to investigate the role of the risk factors in determining these outcomes and whether preoperative removal of some of these risk factors would optimize the results. We conducted a retrospective study analyzing a consecutive series of 255 patients who underwent surgical resection for Crohn's disease between 2010 and 2020. We considered short- and long-term endpoints, such as postoperative complications categorized according to the Clavien–Dindo classification and the appearance of surgical and endoscopic postoperative recurrence. Univariable and multivariable analyses showed that multiple and extensive localizations increased the incidence of postoperative complications (OR = 2.19; 95% CI 1.05–4.5; p = 0.035 and OR = 1.015; 95% CI 1.003–1.028; p = 0.017 for each cm of resected segment, respectively). Regarding theoretically modifiable factors, preoperative hypoalbuminemia (for each g/L reduction) increased the risk of complications with an OR = 1.1; 95% CI 1.02–1.12; p = 0.003. Preoperative steroid therapy exerted a similar effect, with an OR = 2.6; 95% CI 1.1–5.9; p = 0.018. Modifying these last two risk factors by improving the nutritional status or discontinuing steroid therapy significantly reduced complications.Microscopic positivity of the resection margins was a risk factor for surgical recurrence (OR = 8.7; 95% CI 1.9–40; p = 0.05). Based on the results of the present study, surgeons must examine modifiable risk factors, and careful preoperative tailored management may reduce postoperative complications and disease recurrence.

Background Neoadjuvant chemoradiation therapy (nCRT) is the standard treatment modality in locally advanced rectal cancer (LARC). Since response to radiotherapy (RT) is dose dependent in rectal cancer, dose escalation may lead to higher complete response rates. The possibility to predict patients who will achieve complete response (CR) is fundamental. Recently, an early tumour regression index (ERI) was introduced to predict pathological CR (pCR) after nCRT in LARC patients. The primary endpoints will be the increase of CR rate and the evaluation of feasibility of delta radiomics-based predictive MRI guided Radiotherapy (MRgRT) model. Methods Patients affected by LARC cT2-3, N0-2 or cT4 for anal sphincter involvement N0-2a, M0 without high risk features will be enrolled in the trial. Neoadjuvant CRT will be administered using MRgRT. The initial RT treatment will consist in delivering 55 Gy in 25 fractions on Gross Tumor Volume (GTV) plus the corresponding mesorectum and 45 Gy in 25 fractions on the drainage nodes. Chemotherapy with 5-fluoracil (5-FU) or oral capecitabine will be administered continuously. A 0.35 Tesla MRI will be acquired at simulation and every day during MRgRT. At fraction 10, ERI will be calculated: if ERI will be inferior than 13.1, the patient will continue the original treatment; if ERI will be higher than 13.1 the treatment plan will be reoptimized, intensifying the dose to the residual tumor at the 11th fraction to reach 60.1 Gy. At the end of nCRT instrumental examinations are to be performed in order to restage patients. In case of stable disease or progression, the patient will undergo surgery. In case of major or complete clinical response, conservative approaches may be chosen. Patients will be followed up to evaluate toxicity and quality of life. The number of cases to be enrolled will be 63: all the patients will be treated at Fondazione Policlinico Universitario A. Gemelli IRCCS in Rome. Discussion This clinical trial investigates the impact of RT dose escalation in poor responder LARC patients identified using ERI, with the aim of increasing the probability of CR and consequently an organ preservation benefit in this group of patients. Trial registration ClinicalTrials.gov Identifier: NCT04815694 (25/03/2021).

The Italian Society of Colorectal Surgery (SICCR) promoted the project reported here, which consists of a position statement of Italian colorectal surgeons to address the surgical aspects of Crohn's disease management. Members of the society were invited to express their opinions on several items proposed by the writing committee, based on evidence available in the literature. The results are presented, focusing on relevant points. The present paper is not an alternative to available guidelines; rather, it offers a snapshot of the attitudes of SICCR surgeons about the surgical treatment of Crohn's disease. The committee was able to identify some points of major disagreement and suggested strategies to improve quality of available data and acceptance of guidelines.

Miller, WM, Barnes, JT, Sofo, SS, and Wagganer, JD. Comparison of myoelectric activity during a suspension-based and traditional split squat. J Strength Cond Res 33(12): 3236-3241, 2019-Over several decades, traditional resistance training has incorporated body-mass suspension training (SPT), for example, Total-Body Resistance Exercise (TRX); however, very little research has been completed investigating the effects of lower body SPT. Therefore, the purpose of this study was to assess sex differences in myoelectric activity via electromyography while performing a stable (i.e., bench) traditional split squat (TSS) compared with suspension body-mass split squat (TRXSS). Nineteen recreationally active individuals (mean ± SD = men: n = 9; 21.4 ± 2.1 years; 177.2 ± 9.0 cm; 84.2 ± 8.8 kg; women: n = 10; 21.5 ± 1.6 years; 160.7 ± 8.5 cm; 59.1 ± 7.9 kg) participated in this investigation. Subjects performed 3 training sessions, 1 familiarization and 2 (one for each variation) split squat. The TRXSS was performed by placing the rear foot within the foot cradle of the strap, while the TSS required placement of the rear foot on a stable bench (40.64 cm). The TRXSS resulted in higher peak and average myoelectric activity overall, as well as greater gluteus maximus myoelectric activity. No gender or rectus femoris myoelectric activity differences were found. The increased myoelectric activity of the gluteus maximus during the TRXSS was most likely due to increased medial/lateral stabilization demands on the suspended leg. These findings provide insight into TRX as a useful exercise modality for recreationally active or rehabilitative purposes.

Patients with acute severe and medical refractory ulcerative colitis have a high risk of postoperative complications after total abdominal colectomy (TAC). The objective of this retrospective study is to use machine learning to analyze and predict short-term outcomes.32 patients with ulcerative colitis were treated with total abdominal colectomy between 2011 and 2017. Biographical data, preoperative therapy, blood chemistry, nutritional status, surgical technique, blood transfusion and preoperative length of stay were the features selected for the statistical analyses and were used as input for the machine learning algorithms to predict the rate of complications.Traditional statistical analysis showed an overall postoperative morbidity rate of 34% and a mortality rate of 3%. Preoperative low serum albumin levels (2.5 g/dL) were related to a higher risk of minor infectious complications with statistical significance (p0.05). Preoperative length of stay (4 days), blood transfusions (≥1 unit) and body temperature (≥37.5°C) demonstrated a major impact on infectious morbidity with statistical significance (p0.05). Patients treated with steroids and rescue therapy presented a higher risk of minor infectious complications (p0.05). Evaluating only preoperative features, machine learning algorithms were able to predict minor postoperative complications with a high strike rate (84.3%), high sensitivity (87.5%) and high specificity (83.3%) during the testing phase.Machine learning is demonstrated to be useful in predicting the rate of minor postoperative complications in high-risk ulcerative colitis patients, despite the small sample size. It represents a major step forward in data analysis by implementing a retrospective study from a prospective point of view.

There is little information regarding factors that determine dietary diversity among pregnant women in Ghana. The present study, therefore, sought to assess the independent predictors of dietary diversity and its relationship with nutritional status of pregnant women in the Northern Region of Ghana. The present study was an analytical cross-sectional survey involving 423 pregnant women in different stages of gestation. The 24-h dietary recall method was used to assess minimum dietary diversity for women (MDD-W), and nutritional status was assessed using mid-upper arm circumference (MUAC) measurements. Binary logistic regression was performed to assess the association between maternal dietary diversity and maternal thinness and aPvalue of

Background The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) coordinated a five-year study implemented in several countries, including Niger, to provide an evidence-base for programmatic decisions regarding cost-effective approaches to preventive chemotherapy for schistosomiasis control. Methods This was a cluster-randomised trial investigating six possible combinations of annual or biannual community-wide treatment (CWT), school-based treatment (SBT), and holidays from mass treatment over four years. The most intense arm involved two years of annual CWT followed by 2 years of biannual CWT, while the least intensive arm involved one year of annual SBT followed by a year without treatment and two more years of annual SBT. The primary outcome of interest was prevalence and intensity of Schistosoma haematobium among 100 children aged 9–12 years sampled each year. In addition, 100 children aged 5–8 years in their first year of school and 50 adults (aged 20–55 years) were tested in the first and final fifth year of the study. Results In total, data were collected from 167,500 individuals across 225 villages in nine districts within the Niger River valley, Western Niger. Overall, the prevalence of S. haematobium decreased from baseline to Year 5 across all study arms. The relative reduction of prevalence was greater in biannual compared with annual treatment across all arms; however, the only significant difference was seen in areas with a high starting prevalence. Although adults were not targeted for treatment in SBT arms, a statistically significant decrease in prevalence among adults was seen in moderate prevalence areas receiving biannual (10.7% to 4.8%) SBT (P < 0.001). Adults tested in the annual SBT group also showed a decrease in prevalence between Year 1 and Year 5 (12.2% to 11.0%), but this difference was not significant. Conclusions These findings are an important consideration for schistosomiasis control programmes that are considering elimination and support the idea that scaling up the frequency of treatment rounds, particularly in areas of low prevalence, will not eliminate schistosomiasis. Interestingly, the finding that prevalence decreased among adults in SBT arms suggests that transmission in the community can be reduced, even where only school children are being treated, which could have logistical and cost-saving implications for the national control programmes. Graphical Abstract

Under suitable conditions, low-quality, treated urban wastewater (TWW) is an additional water resource for irrigation in water-scarce environments but its use in agriculture requires a careful monitoring of a range of hygiene parameters, including human pathogenic bacteria (HPB). DNA-based microbiological analyses on soil, xylem sap, and leaves surface (phyllosphere) were carried out in an olive (Olea europaea L.) grove located in Southern Italy (Basilicata region). The experimental grove has been managed in two plots for 18 years. The experimental plot (WWtr) was drip irrigated daily with TWW (2800 m3 ha−1 year−1), while the control plot (RFtr) was rainfed. The results of the 16S-rRNA-based metagenomic analysis demonstrated that the phyllosphere had the lowest number of potential HPB (6), compared to soil (22) and xylem (26) compartments. Gammaproteobacteria, including potential HPB, like Pseudomonas and Acinetobacter spp., were significantly higher in WWtr soil and xylem sap, compared to RFtr. A similar trend was observed for Burkholderia spp. (Betaproteobacteria) and Mycobacterium spp. (Actinobacteria). The Firmicutes Enterococcus, Staphylococcus and Streptococcus spp. were more abundant in WWtr xylem sap. The pathogenic Clostridium perfringens was found higher on WWtr leaves (relative abundance 7.17 in WWtr and 1.33 in RFtr) and Enterococcus faecalis in WWtr xylem sap (93.22 in WWtr and 7.08 in RFtr). On the basis of the results obtained, the irrigation with TWW can be considered a realistic and safe agronomic practice in Mediterranean orchards, and an opportunity for farmers and consumers.

The theory of retrograde menstruation as aetiopathogenesis of endometriosis formulated by John Sampson in 1927 shows clear shortcomings: this does not explain why retrograde menstruation is a physiological process that affects 90% of women, while endometriosis occurs in only 10% of cases; it also does not explain the endometriotic foci distant from the pelvis, nor explains the cases of endometriosis in male patients. The immunological alterations of the peritoneal fluid explains the effects of disease, such as the inhibition of the physiological processes of cytolysis, but does not explain the cause. There is evidence to support the hypothesis that ectopic müllerian remnants of the endometrium, endocervix and endosalpinx are items from the genital ridge leaked during organogenesis. It is known that tissues derived from coelomatic epithelial and mesenchymal cells have the potential to metaplastically differentiate into epithelium and stroma. In addition, the phenotype of the ectopic endometrial cells is significantly different from those ectopic. There is scientific evidence that, during organogenesis, the genes of the Homeobox and Wingless family play a fundamental role in the differentiation of the ducts of Muller and development of the anatomical structure of the urogenital tract. We present here a hypothesis that deregulation of genes and the Wnt signaling pathway Wnt/β-catenin leads to aberrations and deregulation within the mesoderm, thus, may cause aberrant placement of stem cells. In addition, immune cells, adhesion molecules, extracellular matrix metalloproteinase and pro-inflammatory cytokines activate/alter peritoneal microenvironment, creating the conditions for differentiation, adhesion, proliferation and survival of ectopic endometrial cells.

Few comparative studies are available on the long-term prognostic role of mesopancreas (MP) excision after pancreaticoduodenectomy (PD). We compared the long-term outcomes of patients undergoing standard PD (sPD) and PD with MP excision (PD-MPe). Sixty sPDs were compared to 60 matched PD-MPe patients for intraoperative and postoperative data, histopathological findings, and long-term outcomes. R0 rate was similar in the two groups (p = 0.17). However, PD-MPe related to a lower rate of MP resection margin positivity (16.7% vs 5%; p = 0.04) and to a higher harvested lymph nodes number (19.8 ± 7.6 vs 10.1 ± 5.1; p

Self-harm rates are increasing globally and demand for supporting, treating and managing young people who engage in self-harm often falls to schools. Yet the approach taken by schools varies. This study aimed to explore the experience of school staff managing self-harm, and to obtain their views on the use of guidelines in their work. Twenty-six pastoral care staff from New Zealand were interviewed. Interviews were analyzed and coded using thematic analysis. Three themes emerged: The burden of the role, discrepancies in expectations, training, and experience, and the need for guidelines to support their work. This research, therefore, demonstrated a need for guidelines to support school staff to provide support around decision making and response to self-harm in the school environment.

The post-management of landfills represents an important challenge for landfill gas treatment. Traditional systems (energy recovery, flares, etc.) present technical problems in treating flow with low methane (CH

The objective of this study was to evaluate the safety of escalating up to 55 Gy within five weeks, the dose of external beam radiotherapy to the previous tumor site concurrently with a fixed daily dose of capecitabine, in patients with resected pancreatic cancer. MATERIAL AND METHODS: Patients with resected pancreatic carcinoma were eligible for this study. Capecitabine was administered at a daily dose of 1600 mg/m (2). Regional lymph nodes received a total radiation dose of 45 Gy with 1.8 Gy per fractions. The starting radiation dose to the tumor bed was 50.0 Gy (2.0 Gy/fraction, 25 fractions). Escalation was achieved up to a total dose of 55.0 Gy by increasing the fraction size by 0.2 Gy (2.2 Gy/fraction), while keeping the duration of radiotherapy to five weeks (25 fractions). A concomitant boost technique was used. Dose limiting toxicity (DLT) was defined as any grade>3 hematologic toxicity, grade>2 liver, renal, neurologic, gastrointestinal, or skin toxicity, by RTOG criteria, or any toxicity producing prolonged (> 10 days) radiotherapy interruption. RESULTS AND DISCUSSION: Twelve patients entered the study (median age: 64 years). In the first cohort (six patients), no patient experienced DLT. Similarly in the second cohort, no DLT occurred. All 12 patients completed the planned regimen of therapy. Nine patients experienced grade 1-2 nausea and/or vomiting. Grade 2 hematological toxicity occurred in four patients. The results of our study indicate that a total radiation dose up to 55.0 Gy/5 weeks can be safely administered to the tumor bed, concurrently with capecitabine (1600 mg/m (2)) in patients with resected pancreatic carcinoma.

The traditionally recognized role of vitamin D consists in the regulation of bone metabolism and calcium-phosphorus homeostasis but recently a lot of in vitro and in vivo studies recognized several “noncalcemic” effects of vitamin D metabolites. Accumulating evidence suggests that the metabolic pathways of this vitamin may play a key role in the developing of gynaecological/obstetric diseases. VDR-mediated signalling pathways and vitamin D levels seem to (deeply) affect the risk of several gynaecological diseases, such as polycystic ovary syndrome (PCOS), endometriosis, and ovarian and even breast cancer. On the other hand, since also the maternal-fetal unit is under the influence of vitamin D, a breakdown in its homeostasis may underlie infertility, preeclampsia, and gestational diabetes mellitus (GDM). According to our literature review, the relationship between vitamin D and gynaecological/obstetric diseases must be replicated in future studies which could clarify the molecular machineries behind their development. We suggest that further investigation should take into account the different serum levels of this vitamin, the several actions which arise from the binding between it and its receptor (taking into account its possible polymorphism), and finally the interplay between vitamin D metabolism and other hormonal and metabolic pathways.

Alzheimer's disease (AD) is a neurodegenerative disorder mainly characterized by amyloid-β (Aβ) plaques, neurofibrillary tangles, loss of synapses and neurons and chronic neuroinflammation. Emerging data highlight the involvement of innate immunity, that has been shown to play opposing roles during the AD progression. Activated microglia and reactive astrocytes exert neuroprotection mediated through Aβ phagocytosis in the early stage, whereas, as the disease progresses, they fail in Aβ clearance and exert detrimental effects, including neuroinflammation and neurodegeneration. Specific toll-like receptors (TLRs) and coreceptors can directly or indirectly be activated to induce Aβ uptake or inflammatory responses, depending on the disease stage. Fibrillar Aβ can directly interact with TLR2, TLR4, and CD14 to induce microglial Aβ phagocytosis in the beginning stages, and neuroinflammatory responses in the late stages. Early TLR3-mediated signal enhances neuronal Aβ autophagy, although it increases neuronal apoptosis in the late AD stage. Similarly, TLR7, TLR8 and TLR9 can enhance microglial Aβ uptake in the early stage, but over time they contribute to neuroinflammation. Therefore, TLRs, and in particular TLR2 and TLR4, represent a suitable target for therapeutic intervention within the disease progression and targeting them carefully could increase Aβ autophagy and phagocytosis or reduce inflammatory responses. Several modulators with selective TLR agonist or antagonist activity have been developed, and many of them could have a therapeutic benefit in AD patients. This paper outlines the role of specific TLRs in AD, also focusing on TLR-targeted compounds yet indicated for the treatment of other inflammatory diseases, that could be used to treat the different stages of the disease.

Purpose: The combination of external radiotherapy (RT) plus intraoperative radiotherapy (IORT) in patients with pancreatic cancer is still debated. This study presents long-term results (minimum follow-up, 102 months) for 26 patients undergoing integrated adjuvant RT (external RT + IORT). Methods and Materials: From 1990 to 1995, a total of 17 patients with pancreatic cancer underwent IORT (10 Gy) and postoperative external RT (50.4 Gy). Preoperative "flash" RT was included for the last 9 patients. The liver and pancreatic head received 5 Gy (two 2.5-Gy fractions) the day before surgery. In the subsequent period (1996-1998), 9 patients underwent preoperative concomitant chemoradiation (39.6 Gy) with 5-fluorouracil, IORT (10 Gy), and adjuvant chemotherapy. Results: Preoperative chemoradiation was completed in all patients, whereas postoperative therapy was completed in 13 of 17 patients. All 26 patients underwent pancreatectomy (25 R0 and one R1 resections). One patient died of postoperative complications (3.8%) not related to IORT. The 9 patients undergoing concomitant chemoradiation were candidates for adjuvant chemotherapy; however, only 4 of 9 underwent adjuvant chemotherapy. At last follow-up, 4 patients (15.4%) were alive and disease free. Disease recurrence was documented in 20 patients (76.9%). Sixteen patients (61.5%) showed distant metastasis, and 5 patients (19.2%) showed local recurrence. The incidence of local recurrence in R0 patients was 4 of 25 (16.0%). The overall 5-year survival rate was 15.4%. There was significant correlation with overall survival of tumor diameter (p = 0.019). Conclusions: The incidence of local recurrence in this long follow-up series (19.2%) was definitely less than that reported in other studies of adjuvant RT (∼50%), suggesting a positive impact on local control of integrated adjuvant RT (IORT + external RT). © 2008 Elsevier Inc. All rights reserved.

Venous thromboembolism (VTE) represents one of the most common and life-threatening extraintestinal complications of inflammatory bowel disease (IBD). Therefore, the prevention of VTE is essential and foremost involves the assessment of individual patient risk factors for VTE and, consequently, the correction of those risk factors that are modifiable. Mechanical and pharmacological prophylaxis are highly effective at preventing VTE in patients hospitalized for acute disease, and they are recommended by the leading guidelines for hospitalized patients with IBD. Unfortunately, several recent surveys reported that prophylaxis against VTE is still poorly implemented because of concerns about its safety and a lack of awareness of the magnitude of thrombotic risk in patients with IBD. Therefore, further efforts are required to increase the thromboprophylaxis rate in these patients to bridge the gap between the best care and standard care and, consequently, to avoid preventable VTE-associated morbidity and mortality. This review provides insight on the critical points that persist on the prevention and treatment of VTE in patients with IBD.

Background:Currently, there is limited evidence on estimates for physical activity (PA) behavior and sedentary behavior (SB) in Ghana. This report card (RC) is intended to increase awareness and sensitivity about issues surrounding PA and SB in Ghana.Methods:Data were collected from peer-reviewed literature, graduate students’ theses, physical education and sports documents, and a survey of opinions of stakeholders covering the 10 key RC indicators and benchmarks. The principal investigator harmonized all grades. A consensus meeting of the RC team was held to assign the final grades.Results:School and Community grades declined from a D in 2014 to an F in 2016. SB declined from B to D. Family and Active Play were not graded in 2014 and now received an F and a B, respectively. Family and Built Environment were graded F, Active Transportation received a C, and Government and Overall PA were graded D.Conclusions:A conscious national investment effort can increase overall PA among children.

Introduction: Non Hodgkin lymphoma-Diffuse large B cell lymphoma (DLBC) is composed of more varieties of one disease. Analysis and understanding of a wide range of characteristics of the disease, which include: clinical, immunohistochemical, cytogenetic and molecular characteristics may improve treatment results. Aim: achieving the estimated three-year survival and influence of IRF/MUM1 expression to three-year survival. Material and methods: A study was retrospective–prospective, patients were followed for seven years a period of dine. The study included 60 patients de novo DLBCL. Age was 18-72 years old, the average age 45 years, male 31 (51,7%) and female 29 (48.3%). Median follow-up was 47 months (3-91 months). To determine differentiation immunophenotype antibodies those were used anti-CD20, anti-CD10, anti-Bcl-6, IRF-4/MUM1, CD 138. Results: Included the GCB type was 65%. Impact prognostic index IPI>2 GBC vs non GBC p=0,038 X2. Statistically significant difference was confirmed compared to the IPI> 2 to 3 year OS p25% has the greatest impact on the disease outcome – three-year survival.

Background: Peroxisome proliferator-activated receptors (PPARs) have demonstrated a lot of important effects in the regulation of glucose and lipid metabolism and in the correct functioning of adipose tissue. Recently, many studies have evaluated a possible effect of PPARs on tumor cells. The purpose of this review is to describe the effects of PPARs, their action and their future prospective; Methods: Narrative review aimed to synthesize cutting-edge evidence retrieved from searches of computerized databases; Results: PPARs play a key role in metabolic diseases, which include several cardiovascular diseases, insulin resistance, type 2 diabetes, metabolic syndrome, impaired immunity and the increasing risk of cancer; in particular, PPARα and PPARβ/δ mainly enable energy combustion, while PPARγ contributes to energy storage by enhancing adipogenesis; Conclusion: PPAR agonists could represent interesting types of molecules that can treat not only metabolic diseases, but also inflammation and cancer. Additional research is needed for the identification of high-affinity, high-specificity agonists for the treatment of obesity, type 2 diabetes (T2DM) and other metabolic diseases. Further studies are needed also to elucidate the role of PPARs in cancer.

In endometriosis, regurgitating endometrial cells fail to undergo apoptosis and implant themselves outside the uterus, particularly in the peritoneum. We studied Fas and FasL behaviour by evaluating the percentages of mFas and mFasL-bearing mononuclear cells from peritoneal fluid, the level of Fas and FasL gene expression at both mRNA and protein levels in the same cells, and the sFas and sFasL values in peritoneal fluid of 80 endometriotic women, at four stages of disease severity. We found no variation in percentage of mFas-bearing mononuclear cells; high and unchanging levels of Fas mRNA and protein, and high and invariable sFas values. Overproduction of sFas antagonises mFas function and plays a role as a decoy in the peritoneal fluid. The mFasL-bearing mononuclear cells and protein levels decreased from the minimal to the severe stage of disease. In contrast to FasL protein, FasL mRNA was overexpressed throughout the course of the disease. sFasL values were high and increased as the disease worsened. Our results showed a non-linear ratio between FasL mRNA and FasL protein levels. Abnormally elevated FasL mRNA may be due to dysregulation in several mechanisms controlling mRNA turnover. The high level of sFasL would be expected to down-regulate FasL activity and compete with the membrane form for mFas binding. As a consequence, mFas-bearing mononuclear cells may be unable to kill and in turn, may themselves become targets for killing by FasL-expressing endometriotic cells.

Background Our objective was evaluate the outcome of primary clinical T4M0 extraperitoneal rectal cancer treated by neoadjuvant radiochemotherapy. Prognosis of clinical T4 rectal cancer is poor. Preoperative chemoradiation therapy may be beneficial. The results obtained are unclear due to lack of objective and strictly applied staging methods. Methods Patients with primary, clinical, T4MO, extraperitoneal rectal cancer, defined by transrectal ultrasonography, computed tomography or magnetic resonance imaging, were considered. Intraoperative radiotherapy and adjuvant chemotherapy were employed in some patients after curative resection (R0). Variables influencing the possibility to perform an R0 resection and a sphincter-saving procedure were investigated as predictors of outcome. Results 100 patients were included. R0 resection was performed in 78 patients. R0 resection rate was greater in females (93% vs 67%) and in responders to neoadjuvant chemoradiation (94% vs 60%). The ability to perform a sphincter-saving procedure was 57%, greater in middle rectal location (85% vs 51%) and in responders to the chemoradiation (70% vs 47%). Median follow-up was 31 months (range, 4–136). Local recurrences were found in 7 patients (10%). Five-year local control in R0 patients was 90% and better in the IORT group (100%). Distant relapse occurred in 24 patients (30%). Five-year overall survival was 59%, and was better after an R0 versus an R1 or R2 resection (68% vs 22%). Overall and disease free survival in R0 patients improved after overall downstaging. Adjuvant chemotherapy given in addition to the neoadjuvant therapy did not appear to offer benefit in improving survival. Conclusion A multimodal approach enabled us to obtain a 5-year overall survival of about 60%. IORT increased local control. The role of adjuvant chemotherapy needs to be further investigated.

The aims of this work are to assess the persistence of rotenone in oil and drupes of olive plants of cultivars Nocellara del Belice (NB) and Cassanese (CA), and to compare the quality of oils from rotenone-treated and untreated plants. Samples of drupes and oil were analyzed at 2, 12, 22 and 30 days after treatment. Rotenone levels in drupes of treated plants declined by about 50% after 22 days from treatment (0.037 mg kg(-1) in NB and 0.039 mg kg(-1) in CA), whereas the respective values in the oil were higher (0.209 mg kg(-1) in NB and 0.229 mg kg(-1) in CA) and had a lower decay half-life (4.02 days in NB and 4.71 days in CA). For both cultivars, no significant differences in oil physicochemical and nutritional parameters were found between the two treatments. The panel test of oils extracted after 22 days did not reveal significant differences in unpleasant aromatic notes nor defects between the two treatments. Our results confirm that serious doubts remain about the safety and healthiness of oils extracted from drupes treated with rotenone. This information could assess the real risk in the use of this product for plant protection in olive growing.

Endometriosis is defined as the presence of endometrial-like endometrial cells, glands and stroma outside the uterus, causing a strong inflammatory-like microenvironment in the affected tissue. This may provoke a breakdown in the peritoneal cavity homeostasis, with the consequent processes of immune alteration, documented by peripheral mononuclear cells recruitment and secretion of inflammatory cytokines in early phases and of angiogenic and fibrogenic cytokines in the late stages of the disease. Considering the pivotal role of interaction between immune and endometriotic cells, in this paper, we aim to shed light about the role of apoptosis pathways in modulating the fine-regulated peritoneal microenvironment during endometriosis.Narrative overview, synthesizing the findings of literature retrieved from searches of computerized databases.In normal conditions, endometriotic cells, refluxed through the fallopian tubes into the peritoneal cavity, should be attacked and removed by phagocytes and NK cells. During endometriosis, the breakdown of peritoneal homeostasis causes the failure of scavenging mechanisms, allowing the survival of endometriotic cells. The consequent so-called "immunoescaping" of endometriotic cells could be due, at least in part, to the reduction of apoptotic-mediated pathways previously described.Considering the large amount of evidence retrieved from in vitro as well as in vivo models, the reduced apoptosis of endometriotic cells together with the increased apoptosis of peritoneal fluid mononuclear cells may address the peritoneal homeostasis to a permissive environment for the progression of the disease.

The physiological changes during pregnancy can significantly alter antiepileptic drug (AED)’s absorption, distribution, metabolism and elimination, thus influencing their plasma concentration. Considering that the risks of using old and new AEDs during pregnancy are still debated, our aim is to review the available evidence on this topic. Narrative overview, synthesizing the findings of literature retrieved from searches of computerized databases. The old AEDs generation (benzodiazepines, phenytoin, carbamazepine, phenobarbital and valproic acid) is teratogenic: minor congenital malformations, such as facial dysmorphism and other anomalies, occur in 6–20 % of infants exposed to AEDs in utero; this value is two times greater than the value reported in the general population. Major congenital malformations (MCM) such as cleft lip and cleft palate, heart defects (atrial septal defect, Fallot’s tetralogy, ventricular septal defect, aortic coarctation, patent ductus arteriosus, and pulmonary stenosis) and urogenital anomalies were estimated to be 4–6 % of infants born from mothers treated with AEDs, compared to 2–3 % of the general population. It is essential to inform women treated with AED that planning pregnancy is necessary, when possible. The problems related to antiepileptic therapy and the possibilities of prenatal diagnosis should be accurately discussed with the patient, when possible before pregnancy: individual circumstances, desire to have children, severity of epilepsy, risks of seizures, family history of congenital malformations and all other potential risk factors must be considered, involving the patient in shared clinical decision-making.

Invariant Natural Killer T cells (iNKT) are a specialized subset of T cells that use their T cell receptor to recognize self and foreign lipids presented by CD1d as cognate antigens. iNKT have been shown to have either protective or harmful roles in many pathological states, including microbial infection, autoimmune disease, allergic disease and cancer. Accumulating evidence seems to suggest that this unique T cell subset combines both classically innate and adaptive immunologic characteristic. Considering these recent data, the aim of work was to review the current knowledge about iNKT in eutopic and ectopic endometrium. Narrative overview, synthesizing the findings of literature retrieved from searches of computerized databases. Currently, the immune paradigm of reproduction is gradually changing shape: recent data confirmed that cytokine milieu influences the development and plasticity of different subtype of mononuclear cells, and in turn it can be influenced by the cytokine production of the latter. Among the different NKT cell populations, the recently characterized iNKT seems to share actions typical both of innate and adaptive immunity, being capable of secreting Th1 as well as Th2 cytokine pattern. Moreover, several subtypes of iNKT were identified, who partially express the same master transcription factors of the corresponding T cells counterpart. Although the data about iNKT’s actions in eutopic and ectopic endometrium are still scarce, it is possible to hypothesize that future investigation can shed light on this point, thus allowing a better knowledge about the regulation of these two microenvironments.

Plants have to counteract unavoidable stress-caused anomalies such as oxidative stress to sustain their lives and serve heterotrophic organisms including humans. Among major enzymatic antioxidants, catalase (CAT; EC 1.11.1.6) and ascorbate peroxidase (APX; EC 1.11.1.11) are representative heme enzymes meant for metabolizing stress-provoked reactive oxygen species (ROS; such as H2O2) and controlling their potential impacts on cellular metabolism and functions. CAT mainly occurs in peroxisomes and catalyzes the dismutation reaction without requiring any reductant; whereas, APX has a higher affinity for H2O2 and utilizes ascorbate (AsA) as specific electron donor for the reduction of H2O2 into H2O in organelles including chloroplasts, cytosol, mitochondria, and peroxisomes. Literature is extensive on the glutathione-associated H2O2-metabolizing systems in plants. However, discussion is meager or scattered in the literature available on the biochemical and genomic characterization as well as techniques for the assays of CAT and APX and their modulation in plants under abiotic stresses. This paper aims (a) to introduce oxidative stress-causative factors and highlights their relationship with abiotic stresses in plants; (b) to overview structure, occurrence, and significance of CAT and APX in plants

Ovarian cancer is one of the most frequent solid tumor that shows clearly biphasic behaviour in response to chemotherapy, with the majority of patients who achieved complete remission after the first cycle of chemotherapy, and subsequently present a relapse which, in most cases, leads to death. Epithelial ovarian cancer (EOC) arises as a consequence of genetic alterations that affect the cells of the ovarian surface, which leads to changes that occur through the activation of oncogenes and inactivation of tumor suppressor genes. The progression of EOC is characterized by a series of combined epigenetic aberrations, including the most important of those determined by the loss of methylation of certain regions of DNA encoding genes such as Ras-association domain-containing family 1 [(RASSF1A) tumor suppressor], death-associated protein kinase [(DAPK) protein kinase associated with the regulation of apoptosis], human sulfa- tase-I [(hSulf-1) sulfatase, which plays a key role in the regulation of apoptosis], breast cancer 1 gene [(BRCA1) tumor suppressor gene, involved in the processes of DNA repair], and HOXAI0 (gene required to promote many transcription factors). To date, accumulating evidence suggests that the initial clinical response is due primarily to the therapeutic efficacy of chemotherapy against differentiated can- cer cells that constitute the bulk of the tumor, whereas the high rate of recurrence is thought to be due to remaining drug-resistant cells, biologically distinct, identified as cancer stem cells (CSC). Current efforts are focusing on genetic and cytological definition of CSC, to guide the development of new diagnostic, and therapeutic perspectives.

PURPOSE: The survival advantage of preoperative radiotherapy in patients with rectal cancer is still a matter of debate, because its incremental benefit in the total mesorectal excision setting is unclear. This study was designed to evaluate early and long-term results of preoperative radiotherapy plus intraoperative radiotherapy in a homogeneous population of T3 middle and lower rectal cancer patients submitted to total mesorectal excision. METHODS: A series of 113 patients with middle and lower T3 rectal cancer consecutively submitted to total mesorectal excision at a single surgical unit from 1991 to 1997 were divided into two groups according to type of neoadjuvant treatment: preoperative radiotherapy (38 Gy) plus intraoperative radiotherapy (10 Gy; n = 69), and no preoperative treatment (total mesorectal excision; n = 44). Standard statistical analyses were used to evaluate early (downstaging, intraoperative factors, hospital morbidity, and mortality rates) and long-term results (recurrence and survival). RESULTS: Overall, 68.2 percent of patients were downstaged by the preoperative regimens (T0 specimens in 3 cases). Postoperative complications were comparable in the two groups. Five-year, disease-specific survival was 81.4 and 58.1 percent in preoperative radiotherapy plus intraoperative radiotherapy group and total mesorectal excision group, respectively (P = 0.052). Corresponding figures for disease-free survival were 73.1 and 57.2 percent in the two groups, respectively (P = 0.096). The rates of local recurrence at five years were 6.6 and 23.2 percent in preoperative radiotherapy plus intraoperative radiotherapy and total mesorectal excision groups, respectively (P = 0.017). CONCLUSIONS: Preoperative radiotherapy plus intraoperative radiotherapy associated with total mesorectal excision reduce local recurrence rate and improve survival in T3 rectal cancer compared with total mesorectal excision alone.

Background. An intensified multidrug chemotherapy regimen (raltitrexed plus oxaliplatin, Tom-Ox) plus concomitant boost radiotherapy, in the neoadjuvant treatment of locally advanced rectal cancer patients, was shown feasible in our previous study. The aim of this study was to evaluate the efficacy in terms of pathologic complete response to pre-operative therapy. Material and methods: A Phase II study was designed and clinical stage T3-T4 and/ or N ≥ 1 patients were treated with concomitant boost radiotherapy (55 Gy/5 weeks) plus concurrent chemotherapy (Tom-Ox). The primary endpoint was the assessment of efficacy in terms of clinical and pathologic response to pre-operative therapy. According to the Gehan's design study, 25 patients were enrolled. Toxicity was assessed according to the RTOG-EORTC and CTCAE v.3.0 criteria. Results: Twenty-five consecutive patients were treated. Twenty-two of the 25 (88%) patients had a partial clinical response at the time of pre-operative magnetic resonance imaging (MRI). Only one patient showed progressive systemic disease at pre-surgical revaluation and was subjected only to biopsy to evaluate pathological response. Twenty-four patients (96%) underwent surgery. Overall, pathologic complete response was observed in eight patients (32%; CI 0.95:12-55%) and only microscopic tumor foci (pTmic) in two patients (pT0-mic: 40%; CI 0.95:18-63%). Nineteen patients (76%) showed tumor down-staging. Proctitis and/or diarrhea were the most frequent acute side effects experienced. Eighteen patients had grade 12 toxicity (77%); whereas two patients experienced grade 3 toxicity (8%). Two-year Local control and actuarial Disease Free Survival were 100% and 91%, respectively. Conclusion. An intensified regimen of concomitant boost radiotherapy plus concurrent raltitrexed and oxaliplatin, can be safely administered in patients with locally advanced rectal cancer. This regimen produces high rates of pathological complete response. Based on available data, this type of treatment could be offered to patients with more advanced tumors (T4 or local recurrence).

Introduction Environmental toxicants can act as endocrine disrupters on the female reproductive system. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is resistant to degradation and due to its lipophilic nature, accumulates in the fat tissue and in the food chain. Human and animal exposure to TCDD affects levels of the steroid receptors and steroid-responsive gene expression and has an impact on metabolism and serum transport of steroids. Gene expression is commonly altered in endometriosis and in the eutopic endometrium of women with the disease. Aberrantly expressed genes include those associated with the regulation of transcription, proliferation, sex steroid metabolism, apoptosis, cell cycle, the immune response and cell adhesion. Methods In this paper, we review the evidence about TCDD’s effect on eutopic and ectopic endometrium, in order to unravel the machinery behind the dysregulation of immune and hormonal homeostasis caused by this environmental toxicant. Conclusion The evidence collected in this review suggests that TCDD could modulate transcription at multiple levels, including the epigenetic level, and via microRNAs, thus disturbing the physiologic processes mediated through the aryl hydrocarbon receptor pathways. Exposure to TCDD also modulates the immune response by influencing the production and action of endometrial cytokines and chemokines, destroying mucosal immunity of the reproductive tract and re-directing the tissue distribution and behavior of leukocytes. Despite this large body of evidence, current human-based epidemiological studies on the association between TCDD and endometriosis remain controversial.

Perturbations in immune processes play an important role in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME), a multifactorial disorder mainly characterized by severe and prolonged fatigue and tipically affecting a variety of bodily systems including the immune system. Recent reports have shown that CFS/ME is an inflammatory disorder may be associated with autoimmune responses, mainly characterized by reduced functional activity of most immune cells, including neutrophils, natural killer cells, monocytes/macrophage and dendritic cells, together with dysregulations in cytokine levels, responsible for changes in the adaptive immune system. Interactions between gut microorganisms and host immune function have been shown to contribute to aberrant inflammation in CFS/ME patients. Commensal and/or pathogen-associated molecular patterns detected by Toll-like receptors (TLRs) expressed on intestinal epithelial cells appear to trigger inflammatory signaling cascade leading to neuroinflammation and neurodegeneration. This paper examines the role of TLR-mediated innate immunity in CFS/ME with evaluation of the current literature, also discussing about innovative therapeutic approaches represented by immunomodulators TLR-targeting.

Endometriosis is a disorder characterised by presence and growth of endometrial tissue outside the uterus, primarily into the peritoneum. The peritoneal fluid (PF) of women with endometriosis undergoes a number of biological changes, including local inflammatory-reparative phenomena and peripheral blood mononuclear cells (PBMC) involvement. These activated cells as well as the endometriotic cells secrete various cytokines with pleiotropic biological activities. Dynamic interplay among cytokines may contribute to realise a favourable microenvironment for the implantation of endometrial cells and the progression of the disease. In the present study, we evaluated the levels of cytokines, such as the tumour necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) in PF and in serum (S) of women with endometriosis to compare their behaviour in both biological fluids. The patients (n = 26) were women of reproductive age attending our observation centre for infertility, diagnosed endometriosis at laparoscopy. Control group (n = 5) consisted of women affected by non-immunologic infertility, diagnosed by explorative laparoscopy. S samples were obtained from peripheral blood before anaesthesia and laparoscopy. PF samples were collected at the time of laparoscopy. Both biological fluids were examined for cytokine by ELISA assays. Our results showed that S and PF levels of TNF-α, not dosable in controls, were very high at the early stage and decreased significantly with the severity of the disease (p < 0.001). TGF-β levels were significantly (p < 0.001) higher than in controls and increased with the severity of the disease (p < 0.001), particularly in the PF. S and PF IL-8 as well as MCP-1 concentrations at all stages were higher than in controls (p < 0.001), yet showed an opposite behaviour in both biological fluids. In fact, S levels of IL-8 and MCP-1 were significantly (p < 0.001) higher at early stages and decreased with the severity of the disease, whereas we observed a significant (p < 0.001) enhancement of these chemokine levels in PF from stage I to stage II and stage III. These observations showed that TNF-α and TGF-β levels were overlapping in S and PF of women with endometriosis. On the contrary, MCP-1 and IL-8 S concentrations decreased with the severity of the disease, whereas PF levels showed markedly increased at severe stages. Taken together the observed changes may be due both to the increased peritoneal macrophage activity and to the larger recruitment of PBMC and autocrine release by endometriotic cells.

Purpose: The objective of this study was to determine the effect on resection rate and survival of neoadjuvant chemoradiotherapy for primarily unresectable locally advanced pancreatic carcinoma. Methods: A systematic review of recently published literature was performed. Resection rates and survival data were derived from reports published from 2000 onwards. Only recent studies, based on radiotherapy with standard dose and fractionation, have been analyzed. Results: Thirteen studies with a total of 510 patients met selection criteria. A resection rate of 8.3-64.2% was reported (median, 26.5%). Of the operated patients, 57.1-100% (median, 87.5%) had R0 tumor resection. Most papers reported occasional pathological complete responses (CR, 3.0-8.8%). When outcome in all patients was considered, median survival ranged from 9 to 23 (median, 13.3) months, comparing favorably with literature data based on concurrent chemoradiation alone (range, 8.6-13 months). Surprisingly, in patients with unresectable tumor at presentation, median survival after surgery ranged from 16.4 to 32.3 (median, 23.6) months. Conclusions: The finding of a high proportion of R0 resection among all resections performed confirms the activity of neoadjuvant radiochemotherapy and should not be neglected. Based on these data, patients with unresectable pancreatic cancer without disease progression after chemoradiotherapy should be considered for radical surgery. © 2009 Society of Surgical Oncology.

Background and purpose: To evaluate the results in terms of dosimetric parameters and acute toxicity of two clinical studies (MARA-1 and MARA-2) on accelerated IMRT-based postoperative radiotherapy. These results are compared with historical control group (CG) of patients treated with "standard" 3D postoperative radiotherapy. Materials and methods: Prescribed dose to the breast was 50.4 Gy in the CG, 40 Gy in MARA-1 (low risk of local recurrence), and 50 Gy in MARA-2 (medium-high risk of recurrence). The tumor bed total dose was 60.4 Gy (sequential 10 Gy electron boost), 44 Gy (concomitant 4 Gy boost), and 60 Gy (concomitant 10 Gy boost) in CG, MARA-1 and MARA-2 studies, respectively. Overall treatment time was of 32 fractions for CG (6.4 weeks); 16 fractions for MARA-1 study (3.2 weeks) and 25 fractions for MARA-2 study (5 weeks). Results: Three hundred and thirty two patients were included in the analysis. Dosimetric analysis showed Dmax and V107% reduction (p < 0.001) and Dmin improvement (p < 0.001) in the PTV in patients treated with IMRT. Grade 2 acute skin toxicity was 33.6%, 13.1%, and 45.1% in the CG, MARA-1, and MARA-2, respectively (p < 0.001), and grade 3 acute skin toxicity was 3.1%, 1.0%, and 2.0%, respectively. Similarly, larger PTV and use of chemotherapy with anthracyclines and taxanes were associated with a greater acute toxicity. With a median follow-up of 31 months, no patients showed local or nodal relapse. Conclusions: A simplified step and shoot IMRT technique allowed better PTV coverage and reduced overall treatment time (CG, 6.6 weeks; MARA-1, 3.2 weeks; MARA-2, 5 weeks) with acceptable short-term toxicity. © 2008 Elsevier Ireland Ltd. All rights reserved.

During endometriosis, a breakdown occurs in endometrial and peritoneal homeostasis caused by cytokine-induced cell proliferation and dysregulation of apoptosis. We studied tumor necrosis factor (TNF)-α, TNF receptor (TNFR) 1, and TNFR2 gene expression at both messenger RNA (mRNA) and protein levels in peritoneal fluid (PF) mononuclear cells (PFMCs), the percentages of these cells bearing the same markers, and soluble TNF-α (sTNF-α) values in PF of 80 women with endometriosis. We found that TNFR1 mRNA and protein levels, the percentages of TNFR1-bearing PFMCs, and sTNF-α values decreased from minimal to severe stages of the disease. Instead, TNF-α and TNFR2 mRNA and protein levels, the percentages of membrane TNF-α (mTNF-α)- and TNFR2-bearing PFMCs increased as the disease worsened. These data allow us to hypothesize that, in early stages, the high percentages of TNFR1-bearing PFMCs and the high levels of sTNF-α could address signal toward complex I pathway, favoring the inflammatory response. With the worsening of the disease, the low percentages of TNFR1-bearing PFMCs are probably due to decreased TNFR1 mRNA transcription and protein translation rate. In early stages (minimal and mild), the percentages of both TNFR2- and mTNF-α-bearing PFMCs are so low, due to decreased mRNA transcription and protein translation rate, that subsequent cellular events may depend minimally by this interaction. The high levels of sTNF-α may be rerouted to bind TNFR1. In contrast, in the moderate and severe stages, the high percentages of TNFR2-bearing PFMCs may be saturated by high percentages of mTNF-α-bearing PFMCs, triggering death process. So, in endometriosis, each component of the TNF-α/TNFRs system may trigger opposite cellular fate.

The aim of the study was to evaluate expression of CD10 in a series of gastrointestinal tumors (GIST) and to find its relationship with prognosis, biological and clinical behavior. GISTs represent the most frequent gastrointestinal (GI) mesenchymal tumors. Biological behavior of GIST cannot be easily predicted; for this reason many biomolecular factors are being investigated to predict prognosis. Recently the role of the CD10 as prognostic predictor in the carcinogenesis of the gastrointestinal carcinomas has been accurately studied. To our knowledge, no data regarding the role of CD10 in GISTs have been published to date.CD10 expression was searched by immunohistochemistry in 29 histological specimens of proved GIST surgically treated. Patients' characteristics and all pathologic features of tumors were statistically reviewed and compared to CD10 expression. Survival analysis was also calculated respect to CD10 expression and relevant clinical or pathological features.CD10 was expressed in 24.1% of cases. There was no correlation between CD10 positivity and risk category, morphology, size or mitosis. The CD10 expression status did not prove to be statistically related to worse prognosis, advanced disease (metastasis) or recurrence, however it was significantly correlated to the tumor site.CD10 expression in our series seems to be associated to a small bowel origin of tumor. CD10 expression alone failed to reveal a statistically significant prognostic value. However survival analysis revealed worse prognosis in stomach tumours with mitotic count10/50 HPF.

Purpose: Best chances of a cure from colorectal cancer are obtained before metastatic spread. Lack of specific tests allowing early diagnosis of the tumor accounts for investigation of gene alterations involved in carcinogenesis by a noninvasive method. In the present study, K-rascodons 12 and 13 mutations were studied in neoplastic cells shed from the bowel into the stool and those contained in the tumor and normal mucosa. Moreover, healthy patients and a few others with precancerous conditions were examined. METHODS: Stool, tumor, and mucosa samples were taken from 25 patients with colorectal adenocarcinoma. Stool and mucosa samples were obtained from 11 healthy patients, and stool, pathologic bowel tissue, and normal mucosa samples were obtained from 3 patients with adenoma (1) or ulcerative colitis (2). Polymerase chain reaction amplification and restriction enzyme analysis were performed. RESULTS: K-rascodon 12 mutations were detected in both tumor and stool samples of 10 cancer patients, and no gene alterations were observed in 14 patients. In one patient with a tumor, a mutation was shown in only the tumor tissue. The agreement rate in tumor and stool analysis was 96 percent. A normal pattern of K-rascodons 12 and 13 was observed in the bowel mucosa. All stool and mucosa samples from healthy patients were not altered in K-ras.Agreement was registered between samples taken from patients with preneoplastic lesions. CONCLUSIONS: These preliminary findings show a high rate of accuracy in the investigation of K-rasalterations in the colorectal cells shed into the feces, suggesting that such an approach could be used to study other gene alterations and, prospectively, to identify early colorectal cancers.

Small-bowel lymphoma is not a common disease, accounting for 15-20% of primary extranodal gastrointestinal lymphomas. Peritoneal lymphomatosis is considered a rare and aggressive presentation. We describe the case of a 55 years-old man affected by T-cell intestinal lymphoma, presenting with diffuse abdominal involvement, bowel dysfunction, severe ascites and pleural effusion, who underwent surgery. Clinical course led dramatically to death. Preoperative cytology and radiologic investigations did not yield diagnosis and were unable to differentiate between peritoneal carcinosis and lymphomatosis. It is suggested that, in such advanced cases, with rapidly deteriorating clinical conditions and huge systemic involvement, surgery is not indicated. On the contrary, maximum effort has to be spent to obtain a preoperative diagnosis.

Purpose To prospectively monitor the response in patients with locally advanced nonmucinous rectal cancer after chemoradiotherapy (CRT) using diffusion-weighted magnetic resonance imaging. The histopathologic finding was the reference standard. Methods and Materials The institutional review board approved the present study. A total of 62 patients (43 men and 19 women; mean age, 64 years; range, 28–83) provided informed consent. T 2 - and diffusion-weighted magnetic resonance imaging scans (b value, 0 and 1,000 mm 2 /s) were acquired before, during (mean 12 days), and 6–8 weeks after CRT. We compared the median apparent diffusion coefficients (ADCs) between responders and nonresponders and examined the associations with the Mandard tumor regression grade (TRG). The postoperative nodal status (ypN) was evaluated. The Mann-Whitney/Wilcoxon two-sample test was used to evaluate the relationships among the pretherapy ADCs, extramural vascular invasion, early percentage of increases in ADCs, and preoperative ADCs. Results Low pretreatment ADCs ( −3 mm 2 /s) were correlated with TRG 4 scores ( p = .0011) and associated to extramural vascular invasion with ypN+ (85.7% positive predictive value for ypN+). During treatment, the mean percentage of increase in tumor ADC was significantly greater in the responders than in the nonresponders ( p 23% ADC increase had a 96.3% negative predictive value for TRG 4. In 9 of 16 complete responders, CRT-related tumor downsizing prevented ADC evaluations. The preoperative ADCs were significantly different ( p = .0012) between the patients with and without downstaging (preoperative ADC ≥1.4 × 10 −3 mm 2 /s showed a positive and negative predictive value of 78.9% and 61.8%, respectively, for response assessment). The TRG 1 and TRG 2–4 groups were not significantly different. Conclusion Diffusion-weighted magnetic resonance imaging seems to be a promising tool for monitoring the response to CRT.

The aim of this study was to assess the efficacy and safety of two closely spaced doses of praziquantel (PZQ) against Schistosoma haematobium and S. mansoni infection in school-aged children, and to characterise re-infection patterns over a 12-month period. The study was carried out in five villages in western Niger: Falmado, Seberi and Libore (single S. haematobium infection foci), and Diambala and Namarigoungou (mixed S. haematobium-S. mansoni infection foci). Parasitological examinations consisted of triplicate urine filtrations and triplicate Kato-Katz thick smears at each visit. Two 40mg/kg oral doses of PZQ were administered 3 weeks apart. Adverse events were monitored within 4h after dosing by the survey team and 24h after treatment using a questionnaire. Our final study cohort comprised 877 children who were infected with either S. haematobium, or S. mansoni, or both species concurrently and received both doses of PZQ. Follow-up visits were conducted 6 weeks, 6 months and 12 months after the first dose of PZQ. At baseline, the geometric mean (GM) infection intensity of S. haematobium ranged from 3.6 (Diambala) to 30.3eggs/10ml of urine (Falmado). The GM infection intensity of S. mansoni ranged from 86.7 (Diambala) to 151.4eggs/g of stool (Namarigoungou). Adverse events were reported by 33.0% and 1.5% of the children after the first and second doses of PZQ, respectively. We found cure rates (CRs) in S. haematobium-infected children 3 weeks after the second dose of PZQ ranging between 49.2% (Falmado) and 98.4% (Namarigoungou) and moderate-to-high egg reduction rates (ERRs) (71.4-100%). Regarding S. mansoni, only moderate CRs and ERRs were found (51.7-58.8% in Diambala, 55.2-60.2% in Namarigoungou). Twelve months post-treatment, prevalence rates approached pre-treatment levels, but infection intensities remained low. In conclusion, PZQ, given in two closely spaced doses, is efficacious against S. haematobium, but the low ERR observed against S. mansoni raises concern about mounting PZQ tolerance.

In this study we have investigated the role of PGE2 in the activation of human T lymphocytes by PWM. A preincubation of these cells with molar concentrations of the prostaglandin ranging from 10(-9) M to 10(-4) M is able to reduce the expression of IL-2R and CD71 on T lymphocyte membrane during the first days of culture, while the DR molecule which is expressed later in the same experimental conditions is not affected by the treatment of T lymphocytes with PGE2. The PGE2-induced inhibition of IL-2R and CD71 well correlates with the reduction of 3H-thymidine incorporation by T cells, indicating that a preincubation of T lymphocytes with PGE2 profoundly affects the proliferative apparatus of these cells when they are stimulated by PWM.

The burden of schistosomiasis in infants and preschool-aged children and their mothers is poorly known. We carried out a cross-sectional epidemiological survey in two villages in Niger: Falmado is endemic for Schistosoma haematobium only, whereas a mixed S. haematobium-S. mansoni focus has been reported from Diambala. The survey examined 282 children (149 girls, 133 boys, average age: 2.6 years) and 224 mothers (average age: 30.1 years). For S. haematobium diagnosis, two urine samples obtained on consecutive days were subjected to the standard urine filtration method. Additionally, macro- and microhaematuria were determined. The diagnosis of S. mansoni was based on a single stool sample with duplicate Kato-Katz thick smears. In Diambala, a standardised, pre-tested questionnaire was administered to mothers, which recorded demographic data, treatment history with anthelminthic drugs, household sanitation and water supply, and bathing practices for their children. Prevalence of egg-patent S. haematobium infections among young children and their mothers was respectively 50.5% and 55.6%, in Falmado, and 60.5% and 72.2% in Diambala. The prevalence of S. mansoni infection in Diambala was 43.8% among children and 52.1% in mothers. Mixed egg-patent infections of S. haematobium and S. mansoni were revealed in 28.6% of the children and 37.3% of the mothers. Questionnaire data showed that 69.8% of the children were accompanied by their mothers to schistosomiasis transmission sites before they were 1 year of age, and that three-quarter of the mothers used water directly drawn from the irrigation canals to wash their children. To conclude, a substantive proportion of children below the age of 5 years had egg-patent schistosomiasis, inclusive of co-infection with S. haematobium and S. mansoni. In the context of schistosomiasis control, more attention should be paid on preschool-aged children and women of childbearing age, so that they can benefit from preventive chemotherapy, which in turn might increase effective coverage of those infected.