Impact of fellow participation on colon adenoma detection rates: a multicenter randomized trial.

BACKGROUND AND AIMS: There are limited and conflicting data on the impact of fellow participation in improving the colon adenoma detection rate. We performed a multicenter randomized controlled trial to evaluate whether fellow involvement might have a beneficial effect on adenoma detection rate. METHODS: The trial was conducted at 4 tertiary hospitals between April and December 2019. Eight hundred twelve patients were randomized to undergo colonoscopy performed by a fellow under the supervision of a staff endoscopist or by an attending physician alone. RESULTS: No significant differences in demographic or adenoma risk factors were detected between the 2 groups. The adenoma detection rate in the intervention group was 44.8% versus 37.1% in the control arm (P = .02). The mean number of adenomas per colonoscopy was significantly higher in the intervention group (0.65 ± 0.3 vs 0.53 ± 0.2 in the control arm, P < .001). The polyp detection rate was 69.7% in the intervention group and 62.5% in the control arm (P = .03), whereas rates of advanced and sessile/serrated adenoma detection were not different between the trial arms (P = .50 and .42, respectively). In the subgroup of more experienced fellows, the adenoma detection rate and polyp detection rate were 49.5% and 75.7%, respectively. No difference was observed between less-experienced fellows and attending physicians alone (P = .53 and 0.86, respectively). The level of bowel preparation and fellow involvement were significant predictors of increased adenoma detection rate in a multivariate analysis. CONCLUSIONS: Our multicenter trial represents the first prospective validation of the beneficial role of fellow involvement in colonoscopy procedures. (Clinical trial registration number: NCT03908229.).

Helicobacter pylori, liver cirrhosis, and portal hypertension: an updated appraisal.

OBJECTIVE: Helicobacter pylori (H. pylori) is the most common cause of gastritis and peptic ulcer. However, H. pylori is even involved in extragastric diseases, and it has been hypothesized that H. pylori could be a risk factor for several hepatic diseases. For instance, a direct involvement of H. pylori in the development of portal hypertension (PH) in cirrhotic patients has been postulated. METHODS: We performed a literature search in major databases to elucidate the relationship between H. pylori, portal hypertension, and liver cirrhosis. RESULTS: The effect of H. pylori on PH may be multifactorial. Endothelial dysfunction, alterations in the vasodilating dynamics, and neoangiogenesis are the most appealing theories about this issue, but the proofs come mainly from experimental studies, therefore a solid pathophysiological basis is still to be demonstrated. Congestive gastropathy (CG) and gastric antral vascular ectasia (GAVE) are two common endoscopic entities responsible for acute/chronic upper gastrointestinal bleeding, and a link with H. pylori has been hypothesized: the gastric mucosa, exposed to H. pylori, could develop both inflammatory microcirculatory alterations and thrombi, resembling the histologic pattern of GAVE. CONCLUSIONS: Despite clues for an association between H. pylori and PH have been shown, these evidences are mostly experimental, therefore, in the absence of a direct proof on human beings, the role of H. pylori in the development of PH is uncertain. However, since this germ may be a cause of peptic ulcer, it should be found and eradicated in cirrhotic patients to reduce the risk of blood loss anemia.

Transarterial chemoembolization: Evidences from the literature and applications in hepatocellular carcinoma patients.

Transarterial chemoembolization (TACE) is the current standard of care for patients with large or multinodular hepatocellular carcinoma (HCC), preserved liver function, absence of cancer-related symptoms and no evidence of vascular invasion or extrahepatic spread (i.e., those classified as intermediate stage according to the Barcelona Clinic Liver Cancer staging system). The rationale for TACE is that the intra-arterial injection of a chemotherapeutic drug such as doxorubicin or cisplatin followed by embolization of the blood vessel will result in a strong cytotoxic effect enhanced by ischemia. However, TACE is a very heterogeneous operative technique and varies in terms of chemotherapeutic agents, treatment devices and schedule. In order to overcome the major drawbacks of conventional TACE (cTACE), non-resorbable drug-eluting beads (DEBs) loaded with cytotoxic drugs have been developed. DEBs are able to slowly release the drug upon injection and increase the intensity and duration of ischemia while enhancing the drug delivery to the tumor. Unfortunately, despite the theoretical advantages of this new device and the promising results of the pivotal studies, definitive data in favor of its superiority over cTACE are still lacking. The recommendation for TACE as the standard-of-care for intermediate-stage HCC is based on the demonstration of improved survival compared with best supportive care or suboptimal therapies in a meta-analysis of six randomized controlled trials, but other therapeutic options (namely, surgery and radioembolization) proved competitive in selected subsets of intermediate HCC patients. Other potential fields of application of TACE in hepato-oncology are the pre-transplant setting (as downstaging/bridging treatment) and the early stage (in patients unsuitable to curative therapy). The potential of TACE in selected advanced patients with segmental portal vein thrombosis and preserved liver function deserves further reports.

Role of Bone Marrow-Derived Stem Cells in Polyps Development in Mice with Apc(Min/+) Mutation.

We explored the hypothesis that an altered microenvironment (intestinal adenomatous polyp) could modify the differentiation program of bone marrow-derived stem cells (BMSCs), involving them in colon carcinogenesis. Sublethally irradiated 8-week-old female Apc(Min/+) mice were transplanted with bone marrow (BM) cells obtained from either male age-matched Apc(Min/+) (Apc-Tx-Apc) or wild type (WT) (WT-Tx-Apc) mice. At 4 and 7 weeks after transplantation, BM-derived colonocytes were recognized by colocalization of Y-chromosome and Cdx2 protein (specific colonocyte marker). Polyp number, volume, and grade of dysplasia were not influenced by irradiation/transplantation procedures since they were similar in both untreated female Apc(Min/+) and Apc-Tx-Apc mice. At 4 and 7 weeks after transplantation, a progressive significant reduction of polyp number and volume was observed in WT-Tx-Apc mice. Moreover, the number of WT-Tx-Apc mice with a high-grade dysplastic polyps significantly decreased as compared to Apc-Tx-Apc mice. Finally, at 4 and 7 weeks after transplantation, WT-Tx-Apc mice showed a progressive significant increase of Y+/Cdx2+ cells in "normal" mucosa, whereas, in the adenomatous tissue, Y+/Cdx2+ cells remained substantially unvaried. Our findings demonstrate that WT BMSCs do not participate in polyp development but rather inhibit their growth. The substitution of genotypically altered colonocytes with Y+/Cdx2+ cells probably contributes to this process.

MEK 1/2 inhibitors in the treatment of hepatocellular carcinoma.

Sorafenib is the only approved systemic treatment for advanced hepatocellular carcinoma patients and all the recently published randomized controlled trials on new systemic drugs have been unsuccessful. This is likely due to a lack of understanding of tumor progression, molecular drivers, and liver toxicity, as well as flaws in trial design. An important signaling pathway in hepatocarcinogenesis is the MEK cascade involved in various cellular responses, including adaptation and survival. A key role in this cascade is played by MEK, of which MEK 1/2 represent the prototypes and an interesting target for new oncological drugs. This review analyzes recent developments and future perspectives on the role of MEK inhibitors in hepatocellular carcinoma treatment.

Liver fibrosis in primary intestinal lymphangiectasia: An undervalued topic.

The relationship between primary intestinal lymphangiectasia (PIL) and liver fibrosis is an emerging topic with many obscure aspects due to the rarity of the disorder. A recent paper reported that a six-month low-fat diet improved liver fibrosis. We report the case of a 17-year-old girl affected by PIL whose hepatic fibrosis progressively worsened within one year, despite dietetic support. This and the previous case report describe extraordinary events, which do not allow clear-cut clinical aspects to be established. Nevertheless, both cases suggest that in patients with PIL, it is necessary to closely monitor liver morphology with in-depth investigations including not only ultrasonography, but also elastography.

Non steroidal anti-inflammatory drug induced damage on lower gastro-intestinal tract: is there an involvement of microbiota?

Intestinal microbiota is composed by a community of microorganisms, which regulate intestinal functions and affect the global health. It is presumable that the well-known intestinal damages induced by Non Steroidal Antiinflammatory Drugs (NSAIDs) mirror on the homeostasis of microbiota, as confirmed by studies investigating this aspect. This review reports the evolving knowledge in this field taking into account both intestinal damage and microbiota involvement. In addition, we analyze a recent study reporting how NSAIDs change intestinal bacterial composition and, on this basis, hypothesize further possible interactions. Indeed, NSAIDs are responsible for a marked reduction of Lactobacilli, which act in the maintenance of luminal pH, mucosal permeability, enterocyte adhesion, mucus production, and immune system modulation. Moreover, Bifidobacteria are involved in the modulation of intestinal motility and local immunity and the demonstrated dangerous effect of NSAIDs could operate through an interference with these functions. A participation of microbiota in mesalazine and salycilate prevention of intestinal cancer may be supposed through their ability to stimulate bacterial production of molecules interfering with cell cycle on the basis of scanty available data. Finally, a supplementation with probiotics in chronic users of NSAIDs may help microbiota remodeling in a damaged intestine, but the poor current knowledge does not allow setting a clear indication for their use despite few evidences of a beneficial effect. In conclusion, it is presumable that the multiple effects of NSAIDs on the lower gastro-intestinal tract may involve microbiota alterations and this consideration suggests further investigations.

Influence of age and type of underlying disease on complications related to home enteral nutrition: a single Italian center experience.

BACKGROUND: No data about the influence of age and underlying diseases on home enteral nutrition (HEN)-related complications are reported in the literature. Herein, we retrospectively investigated this issue by analyzing HEN-related complications in a cohort of consecutive patients grouped according to the underlying disease and age. MATERIAL AND METHODS: We reviewed the medical records of 101 patients referring to our team in 2007-2010 to obtain patients' demographic data, age, nutrition status, duration of HEN treatment, and type of HEN-related complications. They were divided in cancer and neurologic patients and subgrouped on the basis of their age. HEN-related complications were expressed as complication rates. RESULTS: Patients with neurological diseases suffered a significantly higher number of complications as compared with cancer patients (P = .04). Age did not significantly influence complication rates. The mechanical complications were the most frequent. The majority of HEN-related complications were resolved at home. CONCLUSION: Our data strongly suggest that HEN-related complications are influenced by underlying diseases and not by age. In neurologic patients, dementia, loss of autonomy, and the different therapies administered by PEG probably play an important role in increasing the number of HEN-related complications as compared with cancer patients. The most frequent complications can be managed at home, reducing the costs of hospitalizations and discomfort for the patient.

Low molecular weight heparin in portal vein thrombosis of cirrhotic patients: only therapeutic purposes?

Cirrhosis has always been regarded as hemorrhagic coagulopathy caused by the reduction in the hepatic synthesis of procoagulant proteins. However, with the progression of liver disease, the cirrhotic patient undergoes a high rate of thrombotic phenomena in the portal venous system. Although the progression of liver failure produces a reduction in the synthesis of anticoagulant molecules, a test able to detect the patients with hemostatic balance shifting towards hypercoagulability has not yet been elaborated. The need of treatment and/or prophylaxis of cirrhotic patients is demonstrated by the increased mortality, the risk of bleeding from esophageal varices, and the mortality of liver transplantation, when portal vein thrombosis (PVT) occurs even if current guidelines do not give indications about PVT treatment in cirrhosis. In view of the general feeling that the majority of cirrhotic patients at an advanced stage may be in a procoagulant condition (suggested by the sharp increase in the prevalence of PVT), it is presumable that a prophylaxis of this population could be of benefit. The safety and the efficacy of prophylaxis and treatment with enoxaparin in patients with cirrhosis demonstrated by a single paper suggest this option only in controlled trials and, currently, there are no sufficient evidences for a recommendation in the clinical practice.

Lesson from an intriguing case of cryoglobulinemia.

Cryoglobulinemia is a pathological condition usually associated with hepatitis C virus (HCV) chronic liver disease and less commonly with autoimmune or lymphoproliferative disorders. The possible association of cryoglobulinemia with hepatitis B virus (HBV) infection is not widely accepted. In our patient, serum negativity for HCV markers initially led us to consider two other causes of cryoglobulinemia. Myelodysplastic disorders were excluded on the basis of hematological studies, while serum markers for active HBV infection were positive. Surprisingly, the detection of HCV RNA in the cryocrit, even in the absence of anti-HCV antibodies, suggested a pathogenetic role of HCV in this case of cryoglobulinemia. Negative "first level" tests for HCV in the serum do not completely exclude HCV involvement in the pathogenesis of cryoglobulinemia. Analysis of the cryoprecipitate is always essential for diagnosis.

Dietary, endocrine, and metabolic factors in the development of colorectal cancer.

INTRODUCTION: Colorectal cancer is the third cause of death in industrialized countries. Genetic susceptibility and diet are determinant of cancer risk and tumor behavior. Variation in cancer incidence among and within populations with similar dietary patterns suggests that an individual response may reflect interactions with genetic factors, which may modify gene, protein, and metabolite expression patterns. Nutrigenomics, defined as the interaction between nutrition and an individual genome, will likely provide important clues about responders and non-responders to nutritional intervention. DISCUSSION: Epidemiological and experimental studies suggest a protective role of some normal components of daily diet (fish oil, milk, and vegetables), estrogens, and phytoestrogens in colorectal cancer. The effect of estrogen seems to be mediated by their binding to estrogen receptor beta (ER-ß), one of the two estrogen receptors with high affinity for these hormones. Very recently, the demonstration of an involvement of ER-ß in the development of adenomatous polyps of the colon has also been documented, suggesting the use of selective ER-ß agonists in primary colorectal cancer prevention. Phytoestrogens are plant-derived compounds that structurally and functionally act as estrogen agonists in mammals. They are characterized by a higher binding affinity to ER-ß as compared to estrogen receptor alpha (ER-α), the other estrogen receptor subtype. These biological characteristics explain why the administration of phytoestrogens does not produce the classical side effects associated to estrogen administration (cerebro- and cardiovascular accidents, higher incidence of endometrial and breast cancer) and makes these substances potential candidates for colorectal cancer prevention.

Anti-viral therapy in chronic HBV infection: a single centre experience.

BACKGROUND/AIMS: Current treatment of HBV chronic infection is based on interferon (IFN) or nucleoside/nucleotide analogs (NUCs). Seroconversion and resistance rates were evaluated in 135 HBV patients treated with NUCs alone or NUCs+IFN, during the period 1999-2009. METHODOLOGY: Twenty-seven patients were treated with lamivudine (LAM group), 62 with LAM+IFN for 12 months, followed by lamivudine alone (LAM+IFN group). Patients developing lamivudine resistance were added adefovir (add-on) or switched to entecavir. The remaining 46 naive patients received entecavir (ETV group). RESULTS: HBsAg loss was 0% in the LAM and ETV groups, while it reached 8% in the LAM+IFN group. HBe/anti-HBe seroconversion was 20% with NUCs alone but reached 66.6% with NUC+IFN. In the LAM group, resistance was 74% to lamivudine, 47% to adefovir (add-on) and 20% to entecavir (switch). In the LAM+IFN group, resistance to lamivudine was significantly lower in the first 24 months of treatment, reaching 72% by 84 months. In the ETV group, no virological breakthrough was observed. CONCLUSIONS: Our findings suggest a higher percentage of HBe/anti-HBe seroconversion in patients treated with NUCs+IFN as compared to the data reported in the literature when administering interferon or NUCs alone, and substantially confirm the literature data on NUCs resistance.