Helicobacter pylori Secondary Antibiotic Resistance after One or More Eradication Failure: A Genotypic Stool Analysis Study.

Helicobacter pylori (H. pylori) antibiotic resistance is the leading cause for unsuccessful eradication therapy. After one or more failures, the chance of encountering secondary antibiotic resistance increases. The aim of this study was to characterize genotypic secondary resistance in a cohort of southern Italian H. pylori patients with at least one previous failure. Such patients collected stool samples using a dedicated kit (THD fecal testTM), and bacterial DNA was extracted and amplified using RT-PCR. Resistance to clarithromycin, amoxicillin, metronidazole, levofloxacin, and tetracycline was assessed using a high-resolution melting curve. We enrolled 50 patients. A total of 72% of patients failed one previous antibiotic course, 16% failed two, 10% failed three, and 2% failed four. The rate of secondary antibiotic resistance was 16% for clarithromycin, 18% for metronidazole, 14% for amoxicillin, 14% for levofloxacin, and 2% for tetracycline. Among the eight clarithromycin-resistant patients, five (62.5%) previously received a clarithromycin-based regimen. The same rate was 33.3% (3/9) for metronidazole. The only tetracycline-resistant patient had received Pylera. In conclusion, our data seem to show that, even though secondary resistance is not very high, resistance to clarithromycin could be very likely related to previous exposure to this antibiotic.

Concomitant and Bismuth Quadruple Therapy for Helicobacter pylori Eradication in Southern Italy: Preliminary Data from a Randomized Clinical Trial.

Concomitant therapy (CT) and bismuth quadruple therapy (BQT) are recommended in geographical areas with high clarithromycin resistance for Helicobacter pylori (H. pylori) eradication. We compared CT and BQT as the first lines of treatment in a randomized controlled trial. Consecutive patients with H. pylori diagnosed by concordance of both a urea breath test and histology were recruited. For BQT, patients received 3 PyleraTM capsules q.i.d.; for CT, 1000 mg of amoxicillin b.i.d, 500 mg of clarithromycin b.i.d and 500 mg of metronidazole b.i.d. As a proton pump inhibitor, 40 mg of pantoprazole b.i.d was administered. Both regimens lasted 10 days. In total, 46 patients received CT and 38 BQT. Both groups were comparable for age (p = 0.27) and sex (p = 0.36). We did not record any drop outs; therefore, the intention to treat and per protocol rates coincided. The most common symptoms were heartburn and post-prandial fullness, which were equally present in both groups. The success rate was 95.6% for CT and 100% for BQT (p = 0.56). Side effects were recorded in 23.9% and 31.6% of patients in the CT and BQT arms, respectively (p = 0.47). The most common ones were abdominal pain (8) and diarrhea (6). In conclusion, CT and BQT are equally effective in our area with high clarithromycin resistance, southern Italy, and showed comparable safety.

Opioid-induced Constipation: Old and New Concepts in Diagnosis and Treatment.

Daily use of opioid analgesics has significantly increased in recent years due to an increasing prevalence of conditions associated with chronic pain. Opioid-induced constipation (OIC) is one of the most common, under-recognized, and under-treated side effects of opioid analgesics. OIC significantly reduces the quality of life by causing psychological distress, lowering work productivity, and increasing access to healthcare facilities. The economic and social burden of OIC led to the development of precise strategies for daily clinical practice. Key aspects are the prevention of constipation through adequate water intake and fiber support, avoidance of sedentariness, and early recognition and treatment of cofactors that could worsen constipation. Recommended first-line therapy includes osmotic (preferably polyethylene glycol) and stimulant laxatives. Peripherally acting µ-opioid receptor antagonists, such as methylnaltrexone, naloxegol, or naldemedine, should be used in patients that have not responded to the first-line treatments. The bowel functional index is the main tool for assessing the severity of OIC and for monitoring the response. The paper discusses the recent literature on the pathophysiology, clinical evaluation, and management of OIC and provides a pragmatic approach for its assessment and treatment.

Comparison of Transient Elastography and Point Shear Wave Elastography for Analysis of Liver Stiffness: A Prospective Study.

Liver stiffness measurement (LSM) by Fibroscan is the most used non-invasive method to assess liver fibrosis. Recently, point-shear wave elastography (pSWE) has been introduced as a simple alternative non-invasive test. Therefore, we aimed to compare the results of these two techniques. One hundred and eighty-four consecutive patients attending our outpatient ultrasound clinic were recruited. LSM was performed by both Fibroscan and pSWE. Statistical analysis was conducted by Spearman's test for correlation and linear regression. Bland-Altman graphs and ROC curves were drawn with area under the curve (AUC). Overall, the correlation of LS between Fibroscan and pSWE was substantial (r = 0.68, p < 0.001). Linear regression showed a coefficient b= 0.94 ± 0.02. The Bland-Altman plot found a bias of -0.10, with only 11 values exceeding the 95% confidence interval. When only considering patients with a LSM of > 10 kPa (n = 31), we found an excellent r = 0.79 (0.60-0.90, p < 0.001). A cutoff of 12.15 kPa for pSWE had sensitivity = 74.2% and specificity = 99.3% to detect relevant fibrosis, with an AUC = 0.98. The highest correlation was observed for hepatitis C (r = 0.91) and alcoholic liver disease (ALD)(r = 0.99). In conclusion, pSWE shows LSM estimation in agreement with Fibroscan in most cases, and the best concordance was observed for hepatitis C and ALD, and for higher ranges of LS.

Small Intestinal Contrast Ultrasonography (SICUS) in Crohn's Disease: Systematic Review and Meta-Analysis.

The diagnosis of Crohn's Disease (CD) is based on a combination of clinical symptoms, laboratory tests, endoscopy, and imaging data. In Small Intestine Contrast Ultrasonography (SICUS), the ingestion of a macrogol solution as an oral contrast medium may optimize image quality. We performed a meta-analysis to evaluate the diagnostic performance of SICUS for CD. A literature search was performed in August 2023. We selected only studies where SICUS was compared to a technique that allows the assessment of the whole gastrointestinal tract, such as an MRE, a CT scan, or a surgical evaluation. We estimated pooled weighted sensitivity, specificity, and likelihood ratio for positive and negative tests (PLR/NLR) of SICUS. Summary receiver operating characteristic curves (SROC) were drawn, and pooled areas under the curve (AUC) were calculated. Five studies with 325 CD patients were included. SICUS showed a pooled sensitivity for the diagnosis of 95% (95% confidence interval CI 89-99%), a specificity = 77% (95% CI 60-90%), and the AUC was 0.94. SICUS demonstrated a pooled sensitivity for strictures of 78% (95% CI 63-88%) and a specificity = 96% (95% CI 85-99%), with AUC = 0.93. For abscesses, SICUS demonstrated a pooled sensitivity of 100% (95% CI 59-100%) and a specificity of 90% (95% CI 74-98%). Fistulae were detected with a pooled sensitivity of 77% (95% CI 46-95%) and a specificity of 92% (95% CI 75-99%). SICUS demonstrated excellent diagnostic performance compared to the gold standard despite some clinical scenarios (stenosis/fistulae) showing suboptimal diagnostic effectiveness.

Fibres and Colorectal Cancer: Clinical and Molecular Evidence.

Colorectal cancer (CRC) is one of the leading causes of mortality for cancer in industrialized countries. The link between diet and CRC is well-known, and presumably CRC is the type of cancer which is most influenced by dietary habits. In Western countries, an inadequate dietary intake of fibers is endemic, and this could be a driving factor in the increase of CRC incidence. Indeed, several epidemiologic studies have elucidated an inverse relationship between daily fiber intake and risk of CRC. Long-term prognosis in CRC survivors is also dependent on dietary fibers. Several pathogenetic mechanisms may be hypothesized. Fibers may interfere with the metabolism of bile acids, which may promote colon carcinogenesis. Further, fibers are often contained in vegetables which, in turn, contain large amounts of antioxidant agents like resveratrol, polyphenols, or phytoestrogens. Moreover, fibers can be digested by commensal flora, thus producing compounds such as butyrate, which exerts an antiproliferative effect. Finally, fibers may modulate gut microbiota, whose composition has shown to be associated with CRC onset. In this regard, dietary interventions based on high-fiber-containing diets are ongoing to prevent CRC development, especially in patients with high potential for this type of tumor. Despite the fact that outcomes are preliminary, encouraging results have been observed.

Effect of Visual Booklets to Improve Bowel Preparation in Colonoscopy: Systematic Review with Meta-Analysis.

An optimal bowel preparation for colonoscopy is essential to increasing the quality of the examination. Visual booklets have been proposed with conflicting results to enhance bowel preparation. A literature search was performed in March 2023 in the most important databases. Only RCTs were selected. We calculated odd ratios (OR) for dichotomous outcomes. Mean differences (MD) or standardized mean differences (SMD) were used for continuous outcomes. We estimated heterogeneity with the Chi2 and the I2 statistics. In cases of high heterogeneity, a random effect model was used. Six studies were selected, enrolling 1755 patients overall. Adequate bowel preparation was observed in 86.7% of the booklet group versus 77.5% of the control group, with an OR = 2.31 in favor of the booklet. In studies using a 4-L PEG-based preparation, no difference compared to controls was observed, while in non-PEG formulations, preparation with booklets was better than in controls (OR = 5.10, 95% CI 1.82-14.27, p = 0.002). Two studies were performed in an inpatient setting without any differences between booklets and controls, while outpatients receiving booklets had better results (OR = 7.13, 95% CI 5.39-9.45, p < 0.001). The adenoma detection rate was similar between the two groups. In conclusion, booklets are useful to improve bowel preparation. Outpatient settings and preparations not containing PEG could benefit more from booklets.

Familial intestinal polyposis and device assisted enteroscopy: where do we stand?

INTRODUCTION: Hereditary polyposis syndromes are a group of inherited disorders associated with a high risk of developing colorectal cancer. The best known ones are familial adenomatous polyposis (FAP), Peutz-Jeghers (PJS), juvenile polyposis and Cowden syndromes, as well as conditions predisposing to cancer, such as Lynch syndrome. Some of them are characterized by an increased risk of small bowel polyps occurrence. AREAS COVERED: Literature search in PubMed was performed in November 2022 and a narrative review was carried out. Since performing small bowel polypectomy is important in such patients, device assisted enteroscopy (DAE) is the key for this procedure. A screening strategy for small bowel polyps is recommended only for PJS. Guidelines endorse either magnetic resonance imaging (MRI) or videocapsule endoscopy (VCE) every 1-3 years, according to the phenotype of the disease. Enteroscopy should be considered for therapeutic purpose in patients with a positive VCE or MRI. DAE has a central role in the resection of polyps larger than mm or causing symptoms of subocclusion or intussusception. Both single (SBE) and double balloon enteroscopy (DBE) are indicated and able to resect polyps up to 6-10 cm. American guidelines have restricted the indications to small bowel enteroscopy only to FAP patients with grade IV Spiegelman. EXPERT OPINION: Only some groups of patients (PJS, FAP with demonstrated small bowel polyp burden) may benefit from DAE.

Effect of Long-Term Proton Pump Inhibitor Use on Blood Vitamins and Minerals: A Primary Care Setting Study.

BACKGROUND AND OBJECTIVES: Long-term proton pump inhibitor (PPI) use is frequently encountered in primary care. Its effect on micronutrient absorption is known, as vitamin B12, calcium or vitamin D insufficiency may occur in such patients. MATERIALS AND METHODS: We recruited patients using a PPI (pantoprazole) for >12 months. The control group was represented by subjects attending the general practitioner not taking any PPI in the last 12 months. We excluded subjects using nutritional supplements or with diseases interfering with micronutrient blood levels. All subjects underwent blood sampling with full blood count, iron, ferritin, vitamin D, calcium, sodium, potassium, phosphate, zinc and folate. RESULTS: We recruited 66 subjects: 30 in the PPI group and 36 in the control group. Long-term pantoprazole users had lower red blood cell count but similar hemoglobin. We did not find any significant difference in blood iron, ferritin, vitamin B12 and folate. Vitamin D deficit was observed more frequently in the PPI group (100%) than in controls (30%, p < 0.001), with blood levels lower in pantoprazole consumers. No differences in calcium, sodium and magnesium were observed. Pantoprazole users had lower phosphate levels than controls. Finally, a non-significant trend for zinc deficiency was found in PPI users. CONCLUSIONS: Our study confirms that chronic PPI users may encounter alterations in some micronutrients involved in bone mineral homeostasis. The effect on zinc levels deserves further investigation.

Molecular Pathways of Carcinogenesis in Familial Adenomatous Polyposis.

Familial adenomatous polyposis (FAP) is a genetic syndrome characterized by the presence of multiple polyps in the gastrointestinal tract and a wide range of systemic extra-intestinal manifestations. Patients affected will inevitably undergo abdominal surgery due to the malignant transformation of one or more adenomas. The pathogenesis of the disease is based on a loss of function mutation in adenomatous polyposis coli (APC), a tumor-suppressor gene, inherited following a Mendelian pattern. This gene is a key component of multiple cell functions that cooperate for homeostasis; when mutated, it contributes to the progression of colorectal adenoma into cancer. Recent studies have demonstrated that several additional mechanisms may influence this process, such as alterations in gut microbiota composition and mucosal barrier immunity, interaction with the immune microenvironment and inflammation, the hormone estrogen, and other signaling pathways. These factors represent promising targets of future therapies and chemoprevention, aiming to alter the progressive nature of the disease and improve the quality of life of families affected. Therefore, we performed a narrative review about the current knowledge of the aforementioned pathways involved in colorectal cancer pathogenesis in FAP, exploring the genetic and environmental factors that may contribute to the development of CRC in FAP.

The State of the Art of Molecular Fecal Investigations for Helicobacter pylori (H. pylori) Antibiotic Resistances.

A new paradigm shift for the treatment of Helicobacter pylori (H. pylori) infection would be timely due to a progressive increase in antibiotic resistance. Such a shift in the perspective of the H. pylori approach should include the preliminary assessment of antibiotic resistance. However, the availability of sensitivity tests is not widespread and the guidelines have always indicated empirical treatments without taking into account the need to make sensitivity tests accessible, i.e., the necessary starting point for improving results in different geographical areas. Currently, the traditional tools for this purpose (culture) are based on performing an invasive investigation (endoscopy) and often involve technical difficulties; thus, they were only confined to the settings where multiple attempts at eradication have failed. In contrast, genotypic resistance testing of fecal samples using molecular biology methods is much less invasive and more acceptable to patients. The purpose of this review is to update the state of the art of molecular fecal susceptibility testing for the management of this infection and to extensively discuss the potential benefits of their large-scale deployment, i.e., novel pharmacological opportunities.

A prospective study on Helicobacter pylori rapid urease test false negativity: is it time for its use in restricted situations?

BACKGROUND: Rapid urease test (RUT) is a diagnostic tool for Helicobacter pylori (H. pylori) diagnosis, based on the ability of the bacterium to produce urease. Despite it is considered simple, fast, and cheap, some conditions may cause false negativity. Therefore, the aim of this study was to compare RUT with currently recommended tests for H. pylori diagnosis. METHODS: We enrolled consecutive patients who underwent upper endoscopy with histology, RUT, and urea breath test (UBT). Delta over baseline (DOB) >4% was considered positive for UBT. Diagnosis of infection was achieved when at least two tests were positive. The rate of false positivity of RUT was computed, and DOB value in RUT+ versus RUT- was compared by Mann-Whitney Test. RESULTS: One hundred and sixteen consecutive patients with H. pylori infection were recruited. The male/female ratio was 35/81 and the mean age 45.2±13.1. Twenty-five patients (21.5%) were RUT-, despite being positive at both histology and UBT. On the other hand, in only two patients UBT and histology had discordant results. A full concordance of the three tests was observed in 89 patients (76.7%). DOB, additionally, was significantly higher in RUT+ patients (39.2±24.2%) than RUT- ones (26.3±18.5%; P=0.005). CONCLUSIONS: RUT shows false negativity rate higher than 20%. Moreover, the RUT-negative patients showed a lower DOB at UBT, which is an indirect indicator of intragastric bacterial load. Therefore, it is presumable that H. pylori low amount may be a concurrent cause of false negativity. This study suggests that RUT-based H. pylori detection should be restricted to some specific conditions.

Rifabutin as salvage therapy for Helicobacter pylori eradication: Cornerstones and novelties.

When several Helicobacter pylori eradication treatments fail, guidelines recommend a cultured guided approach; however, culture is not widely available. Therefore, a rifabutin based regimen could be the best solution. Rifabutin indeed shows a low rate of antibiotic resistance. Rifabutin is generally used in combination with amoxicillin in a triple therapy, with eradication rates about 80% in third-line regimens. The ideal duration of this therapy should range between 10 and 12 d. Combinations with antibiotics other than amoxicillin have demonstrated even better results, such as vonoprazan, which is a type of novel acid suppressor drug. Finally, a new formulation of triple therapy in a single capsule is under investigation, which is a field that deserves further investigation. Some notes of caution about rifabutin should be mentioned. This drug is used to treat tuberculosis or atypical mycobacteria; therefore, before starting a rifabutin-based eradication regimen, Mycobacterium tuberculosis infection should be thoroughly tested, since its use could promote the development of antibiotic resistance, thus affecting its effectiveness against Koch's bacillus. Additionally, some serious side effects must be evaluated before starting any rifabutin-based therapy. Adverse effects include fever, nausea, vomiting and bone marrow suppression. For this reason, full blood count surveillance is required.

Effect of metronidazole resistance on Helicobacter pylori eradication regimens.

OBJECTIVES: Guidelines suggest bismuth-containing quadruple therapy (BQT) or concomitant therapy (CT) as first-line therapy in our geographic area. Both schedules contain metronidazole. We aimed to evaluate the effect of metronidazole resistance to Helicobacter pylori (H. pylori) eradication therapy. METHODS: We recruited treatment-naïve subjects with H. pylori infection who received either CT or BQT during January 2020 and December 2021. Before therapy, a fecal sample was collected using the THD fecal test device from each patient. H. pylori DNA was extracted and mutations of rdxA and frxA genes and A2143G for metronidazole and clarithromycin resistance were investigated using real-time polymerase chain reaction with a high-resolution melting curve. RESULTS: Ninety-six patients were enrolled, including 29 received BQT and 67 received CT. The overall eradication rate was 94.8% (100% for BQT and 92.5% for CT). Metronidazole resistance was found in 18 (18.8%) subjects, while clarithromycin resistance was found in 19 (19.8%). All 18 patients with metronidazole resistance achieved successful eradication (five treated with BQT and 13 with CT). The eradication rate in metronidazole-sensitive strains was 93.6%. Of these, 24 received BQT with 100% success, and 54 had CT with five failures (successful eradication in 90.7%). Two patients with treatment failure were resistant to clarithromycin, and the remaining three were susceptible to both clarithromycin and metronidazole. No statistical significance was observed in the eradication rate between metronidazole-resistant and -sensitive strains (100% vs 93.6%, P = 0.58). CONCLUSION: Metronidazole resistance does not influence the eradication rate of BQT and CT regimens in our geographical area, even if such results need to confirmed in a larger sample.

Serrated Colorectal Lesions: An Up-to-Date Review from Histological Pattern to Molecular Pathogenesis.

Until 2010, colorectal serrated lesions were generally considered as harmless lesions and reported as hyperplastic polyps (HPs) by pathologists and gastroenterologists. However, recent evidence showed that they may bear the potential to develop into colorectal carcinoma (CRC). Therefore, the World Health Organization (WHO) classification has identified four categories of serrated lesions: hyperplastic polyps (HPs), sessile serrated lesions (SSLs), traditional serrated adenoma (TSAs) and unclassified serrated adenomas. SSLs with dysplasia and TSAs are the most common precursors of CRC. CRCs arising from serrated lesions originate via two different molecular pathways, namely sporadic microsatellite instability (MSI) and the CpG island methylator phenotype (CIMP), the latter being considered as the major mechanism that drives the serrated pathway towards CRC. Unlike CRCs arising through the adenoma-carcinoma pathway, APC-inactivating mutations are rarely shown in the serrated neoplasia pathway.

Second-line Therapy for Helicobacter Pylori Eradication: State of the Art.

Helicobacter pylori (H. pylori) is a Gram negative spiraliform bacterium that colonizes the human stomach. It is the most common cause of chronic gastritis, peptic ulcer, and gastric carcinoma. The eradication therapy is based on the combination of a proton pump inhibitor and several antibiotics such as amoxicillin, metronidazole, clarithromycin, levofloxacin or tetracycline. The most commonly used regimens for eradication in the first line are triple, sequential and concomitant therapy, despite the last European Guidelines suggesting a quadruple therapy already at the first attempt in areas with high resistance rates. However, the rise in antibiotic resistance is the main reason for a marked increase in first-line therapy failure. Clarithromycin resistancea, is especially acknowledged as the most important event resulting in failure. Up to 20% of patients are intended not to eradicate, therefore they will need a second line therapy. Currently, the most used rescue regimens are levofloxacin-based triple therapy and bismuth-containing quadruple therapy, despite guidelines suggesting to use a combination of antibiotics that have not been included in previous treatments. Nitazoxanide is a novel antibiotic with promising results. Additionally, an interesting field worth of investigation is the antibiotic susceptibility based approach, which could help choose antibiotics with confirmed effectiveness in vitro. Analysis of antibiotic resistance may be performed by both bacterial culture and molecular biology techniques, able to detect point mutations conferring resistance. This is a particularly interesting approach, since it may personalize the therapy, thus optimizing the regimen and maximizing the probability of success.

Empiric "Three-in-One" Bismuth Quadruple Therapy for Second-Line Helicobacter pylori Eradication: An Intervention Study in Southern Italy.

The eradication of Helicobacter pylori (H. pylori) may be difficult due to antibiotic resistance. Indeed, after one failure, a second-line therapy is needed and a bismuth containing quadruple therapy (BQT) with a three-in-one capsule formulation is becoming very popular. Therefore, we aimed to evaluate effectiveness and safety of BQT as a second-line therapy. We recruited consecutive patients with one therapy failure. For ten days patients received the three-in-one BQT Pylera® therapy, in combination with a proton-pump inhibitor (PPI), decided at the choice of the investigator, at full dose bid. The eradication rate was calculated by intention-to-treat (ITT) and per-protocol (PP)analyses and 95% confidence intervals (CI) were calculated. Seventy-three patients were recruited, 41 females and 32 males (mean age 53.0±13.1 years). Fifty-five patients failed triple therapy with amoxicillin and clarithromycin and the remaining 18 received sequential therapy. Seventy-two patients consumed at least 90% of the capsules, while only one did not complete the therapy due to adverse events (nausea and diarrhea). By ITT analysis, BQT was successful in 62 subjects (eradication rate 84.9%, 95%CI 76.7-93.1%). By PP analysis, the eradication rate was 86.1% (95%CI 78.1-94.1%).Adverse events were observed in 14 subjects (20.5%).In conclusion, our report confirmed that BQT is effective as an empiric second-line regimen.

Small Bowel Metastatic Melanoma: An Emblematic "Coal-Black" Appearance at Videocapsule Endoscopy.

A 80-year-old woman underwent vulvar melanoma resection and segmental lung resection for pulmonary metastasis. Immunotherapy with Nivolumab was performed. One year later, the patient was admitted for gastrointestinal (GI) recurrent bleeding and severe anemia. Esophagoastroduodenoscopy and colonoscopy did not show any abnormality, while videocapsule endoscopy (VCE) revealed an irregular and exophytic whitish area with a "coal-black" central depression. Small bowel resection was performed and histological examination revealed S100 protein strongly positive melanoma metastasis. The patient died six months later from disease progression. A "coal-black" appearance of intestinal metastatic melanoma has been described only twice before this report. In one case the patient had been treated by immunotherapy with interferon A and dendritic cell-based vaccination. In our patient, it is presumable that the picture we observed was a consequence of Nivolumab treatment inducing the disappearance of melanocytes in the area surrounding the metastasis with the onset of the central coal-black lesion encircled by whitish tissue. This picture should be emblematic of intestinal metastatic melanoma in subjects treated with immunotherapy showing occult/obscure bleeding.

Liver involvement in inflammatory bowel disease: What should the clinician know?

Inflammatory bowel disease (IBD) may show a wide range of extraintestinal manifestations. In this context, liver involvement is a focal point for both an adequate management of the disease and its prognosis, due to possible serious comorbidity. The association between IBD and primary sclerosing cholangitis is the most known example. This association is relevant because it implies an increased risk of both colorectal cancer and cholangiocarcinoma. Additionally, drugs such as thiopurines or biologic agents can cause drug-induced liver damage; therefore, this event should be considered when planning IBD treatment. Additionally, particular consideration should be given to the evidence that IBD patients may have concomitant chronic viral hepatitis, such as hepatitis B and hepatitis C. Chronic immunosuppressive regimens may cause a hepatitis flare or reactivation of a healthy carrier state, therefore careful monitoring of these patients is necessary. Finally, the spread of obesity has involved even IBD patients, thus increasing the risk of non-alcoholic fatty liver disease, which has already proven to be more common in IBD patients than in the non-IBD population. This phenomenon is considered an emerging issue, as it will become the leading cause of liver cirrhosis.

Estrogen Receptors in Colorectal Cancer: Facts, Novelties and Perspectives.

Colorectal cancer (CRC) is the second cause of cancer-related death in both sexes worldwide. As pre-menopausal women are less likely to develop CRC compared to age-matched men, a protective role for estrogens has been hypothesized. Indeed, two isoforms of nuclear estrogen receptors (ER) have been described: ERα and ERß. While the binding of 17beta-estradiol to ERα activates anti-apoptotic pathways, the interaction with ERß activates caspase-3, inducing apoptosis. In this regard, several pieces of evidence show that ERß tends to be under-regulated in advanced adenomas and CRC, with an opposite trend for ERα. Furthermore, ERß stimulation slows adenomatous polyp growth and modulates relevant CRC pathways. Based on such considerations, dietary modulation of ER is promising, particularly in subjects with genetic predisposition for CRC. Nevertheless, the main limitation is the lack of clinical trials on a large population scale.