Venous thrombosis and prothrombotic factors in inflammatory bowel disease

Patients with inflammatory bowel disease(IBD)may have an increased risk of venous thrombosis(VTE).PubMed,ISI Web of Knowledge and Scopus were searched to identify studies investigating the risk of VTE and the prevalence of acquired and genetic VTE risk factors and prothrombotic abnormalities in IBD.Overall,IBD patients have a two-to fourfold increased risk of VTE compared with healthy controls,with an overall incidence rate of 1%-8%.The majority of studies did not show significant differences in the risk of VTE between Crohn’s disease and ulcerative colitis.Several acquired factors are responsible for the increased risk of VTEin IBD:inflammatory activity,hospitalisation,surgery,pregnancy,disease phenotype(e.g.,fistulising disease,colonic involvement and extensive involvement)and drug therapy(mainly steroids).There is also convincing evidence from basic science and from clinical and epidemiological studies that IBD is associated with several prothrombotic abnormalities,including initiation of the coagulation system,downregulation of natural anticoagulant mechanisms,impairment of fibrinolysis,increased platelet count and reactivity and dysfunction of the endothelium.Classical genetic alterations are not generally found more often in IBD patients than in nonIBD patients,suggesting that genetics does not explain the greater risk of VTE in these patients.IBD VTE may have clinical specificities,namely an earlier first episode of VTE in life,high recurrence rate,decreased efficacy of some drugs in preventing further episodes and poor prognosis.Clinicians should be aware of these risks,and adequate prophylactic actions should be taken in patients who have disease activity,are hospitalised,are submitted to surgery or are undergoing treatment.     

Hematologic diseases: High risk of Clostridium difficile associated diarrhea

AIM:To investigate the incidence and clinical outcome of Clostridium difficile(C.difficile)associated diarrhea(CDAD)in patients with hematologic disease.METHODS:We retrospectively reviewed the medical records of patients who underwent C.difficile testing in a tertiary hospital in 2011.The incidence and risk factors for CDAD and its clinical course including recurrence and mortality were assessed in patients with hematologic disease and compared with those in patients with nonhematologic disease.RESULTS:About 320 patients were diagnosed with CDAD(144 patients with hematologic disease;176with nonhematologic disease).The incidence of CDAD in patients with hematologic disease was estimated to be 36.7 cases/10000 patient hospital days,which was higher than the 5.4 cases/10000 patient hospital days in patients with nonhematologic disease.Recurrence of CDAD was more frequent in patients with hematologic disease compared to those with nonhematologic disease(18.8%vs 8.5%,P<0.01),which was associated with higher re-use of causative antibiotics for CDAD.Mortality due to CDAD did not differ between the two groups.Multivariate analysis showed that intravenous immunoglobulin was the only significant factor associated with a lower rate of recurrence of CDAD in patients with hematologic disease.CONCLUSION:The incidence and recurrence of CDAD was higher in patients with hematologic disease than in those with nonhematologic disease.     

Hepatocellular carcinoma recurrence after liver transplantation: Risk factors,screening and clinical presentation

Liver transplantation is the best treatment option for cirrhotic patients with earlystage hepatocellular carcinoma, but it faces the problem of scarcity of donors and the risk of tumor recurrence, which affects between 15% and 20% of the cases,despite the use of restrictive criteria. The risk of recurrence depends on a number of factors, related to the tumor, the patient, and the treatment, which are discussed in this review. Some of these factors are already well established, such as the histopathological characteristics of the tumor, Alpha-fetoprotein(AFP)levels, and waiting time. Other factors related to the biological behavior of the tumor and treatment should be recognized because they can be used in the refinement of the selection criteria of transplant candidates and in an attempt to reduce recurrence. This review also discusses the clinical presentation of recurrence and its prognosis, contributing to the identification of a subgroup of patients who may have better survival, if they are timely identified and treated.Development of recurrence after the first year, with AFP levels ≤ 100 ng/mL, and single site capable of locoregional therapy are associated with better survival after recurrence.     

Chronic hepatitis C genotype 1 virus: Who should wait for treatment?

Elucidation of the natural history of chronic hepatitis C(CHC)and the identification of risk factors for its progression to advanced liver disease have allowed many physicians to recommend deferral treatment(triple therapy)in favour of waiting for new drug availability for patients who are at low risk of progression to significant liver disease.Newer generation drugs are currently under development,and are expected to feature improved efficacy and safety profiles,as well as less complex and shorter duration delivery regimens,compared to the current standards of care.In addition,patients with cirrhosis and prior null responders have a low rate(around 15%)of achieving sustained virological response(SVR)with triple therapy,and physicians must also consider the decision to wait for new treatments in the future for these patients as well.Naive patients are the most likely to achieve a close to 100%SVR rate;therefore,it may be advisable to recommend that patients with mild to moderate CHC should wait for the newer therapy options.In contrast,patients with advanced fibrosis and cirrhosis will be those with the greatest need for expedited therapeutic intervention.There remains a need,however,for establishing definitive clinical management guidelines to maximize the benefit of waiting for new drugs and minimize risk of side effects and non-response to the current triple therapy.     

Clinical management of inflammatory bowel disease in the organ recipient

There was estimated a higher incidence of de novo inflammatory bowel disease(IBD)after solid organ transplantation than in the general population.The onset of IBD in the organ transplant recipient population is an important clinical situation which is associated to higher morbidity and difficulty in the medical therapeutic management because of possible interaction between anti-reject therapy and IBD therapy.IBD course after liver transplantation(LT)is variable,but about one third of patients may worsen,needing an increase in medical therapy or a colectomy.Active IBD at the time of LT,discontinuation of 5-aminosalicylic acid or azathioprine at the time of LT and use of tacrolimusbased immunosuppression may be associated with an unfavorable outcome of IBD after LT.Anti-tumor necrosis factor alpha(TNFα)therapy for refractory IBD may be an effective and safe therapeutic option after LT.The little experience of the use of biological therapy in transplanted patients,with concomitant anti-rejection therapy,suggests there be a higher more careful surveillance regarding the risk of infectious diseases,autoimmune diseases,and neoplasms.An increased risk of colorectal cancer(CRC)is present also after LT in IBD patients with primary sclerosing cholangitis(PSC).Anannual program of endoscopic surveillance with serial biopsies for CRC is recommended.A prophylactic colectomy in selected IBD/PSC patients with CRC risk factors could be a good management strategy in the CRC prevention,but it is used infrequently in the majority of LT centers.About 30%of patients develop multiple IBD recurrence and 20%of patients require a colectomy after renal transplantation.Like in the liver transplantation,anti-TNFαtherapy could be an effective treatment in IBD patients with conventional refractory therapy after renal or heart transplantation.A large number of patients are needed to confirm the preliminary observations.Regarding the higher clinical complexity of this subgroup of IBD patients,a close multidisciplinary approach between an IBD dedicated gastroenterologist and surgeon and an organ transplantation specialist is necessary in order to have the best clinical management of IBD after transplantation.     

Non-alcoholic fatty liver disease: What has changed in the treatment since the beginning?

Non-alcoholic fatty liver disease(NAFLD) is an umbrella term to describe the entire spectrum of this common liver disease. In patients with NAFLD, especially those with non-alcoholic steatohepatitis(NASH), most often have one or more components of the metabolic syndrome, but this is not universal. Although most patients with NAFLD share many clinical features, only a subset of patients develops significant liver inflammation and progressive fibrosis. On the other hand, not all patients with NASH exhibit insulin resistance. NASH can be seen in patients who are lean and have no identifiable risk factors. Many clinical studies have tried numerous drugs and alternative medicine, however, investigators have failed to identify a safe and effective therapy for patients with NASH. As summarized, the heterogeneity of pathogenic pathways in individual patients with NASH may warrant the development of an individualized treatment according to the underlying pathogenic pathway. The differentiation of pathogenetic targets may require the development of diagnostic and prognostic biomarkers, and the identification of genetic susceptibilities. At present, evidence-based medicine provides only a few options including life-style modifications targeting weight loss, pioglitazone and vitamin E in non-diabetic patients with biopsy-proven NASH.     

Preventing infective complications in inflammatory bowel disease

Over the past decade there has been a dramatic change in the treatment of patients with Crohn’s disease and ulcerative colitis,which comprise the inflammatory bowel diseases(IBD).This is due to the increasing use of immunosuppressives and in particular the biological agents,which are being used earlier in the course of disease,and for longer durations,as these therapies result in better clinical outcomes for patients.This,however,has the potential to increase the risk of opportunistic and serious infections in these patients,most of which are preventable.Much like the risk for potential malignancy resulting from the use of these therapies long-term,a balance needs to be struck between medication use to control the disease with minimization of the risk of an opportunistic infection.This outcome is achieved by the physician’s tailored use of justified therapies,and the patients’education and actions to minimize infection risk.The purpose of this review is to explore the evidence and guidelines available to all physicians managing patients with IBD using immunomodulating agents and to aid in the prevention of opportunistic infections.     

Management of hepatitis B reactivation in immunosuppressed patients: An update on current recommendations

The proportion of hepatitis B virus(HBV) previously exposed patients who receive immunosuppressive treatment is usually very small. However, if these individuals are exposed to potent immunosuppressive compounds, the risk of HBV reactivation(HBVr) increases with the presence of hepatitis B surface antigen(HBsAg) in the serum. Chronic HBsAg carriers have a higher risk than those who have a total IgG anticore as the only marker of resolved/occult HBV disease. The loss of immune control in these patients may results in the reactivation of HBV replication within hepatocytes. Upon reconstitution of the immune system, infected hepatocytes are once again targeted and damaged by immune surveillance in an effort to clear the virus. There are different virological scenarios, and a wide spectrum of associated drugs with specific and stratified risk for the development of HBVr. Some of this agents can trigger a severe degree of hepatocellular damage, including hepatitis, acute liver failure, and even death despite employment of effective antiviral therapies. Currently, HBVr incidence seems to be increasing around the world; a fact mainly related to the incessant appearance of more powerful immunosuppressive drugs launched to the market. Moreover, there is no consensus on the length of prophylactic treatment before the patients are treated with immunosuppressive therapy, and for how long this therapy should be extended once treatment is completed. Therefore, this review article will focus on when to treat, when to monitor, what patients should receive HBV therapy, and what drugs should be selected for each scenario. Lastly, we will update the definition, risk factors, screening, and treatment recommendations based on both current and different HBV management guidelines.     

Stimulating erythropoiesis in inflammatory bowel disease associated anemia

Anemia is a frequent complication in patients with inflammatory bowel disease (IBD), and is associated with decreased quality of life and increased rate of hospitalization. The primary therapeutic targets of IBD- associated anemia are iron deficiency and anemia of chronic disease. An important prognostic parameter of the success or failure of therapy is the outcome of the underlying disease. Iron deficiency should be appropriately managed with iron supplementation. However, the use of oral iron therapy is limited by several problems, the most important being gastrointestinal side effects leading occasionally to disease relapse and poor iron absorption. Intravenous iron preparations are more reliable, with iron sucrose demonstrating the best efficacy and tolerability. Treatment with erythropoietin or darbepoetin has been proven to be effective in patients with anemia, who fail to respond to intravenous iron. Patients with ongoing inflammation have anemia of chronic disease and may require combination therapy comprising of intravenous iron sucrose and erythropoietin. After initiating treatment, careful monitoring of hemoglobin levels and iron parameters is needed in order to avoid recurrence of anemia. In conclusion, anemia in the setting of IBD should be aggressively diagnosed, investigated, and treated. Future studies should define the optimal dose and schedule of intravenous iron supplementation and appropriate erythropoietin therapy in these patients.     

Neoadjuvant radiotherapy for rectal cancer management

Thirty per cent of all colorectal tumours develop in the rectum.The location of the rectum within the bony pelvis and its proximity to vital structures presents significant therapeutic challenges when considering neoadjuvant options and surgical interventions.Most patients with early rectal cancer can be adequately managed by surgery alone.However,a significant proportion of patients with rectal cancer present with locally advanced disease and will potentially benefit from down staging prior to surgery.Neoadjuvant therapy involves a variety of options including radiotherapy,chemotherapy used alone or in combination.Neoadjuvant radiotherapy in rectal cancer has been shown to be effective in reducing tumour burden in advance of curative surgery.The gold standard surgical rectal cancer management aims to achieve surgical removal of the tumour and all draining lymph nodes,within an intact mesorectal package,in order to minimise local recurrence.It is critically important that all rectal cancer cases are discussed at a multidisciplinary meeting represented by all relevant specialties.Pre-operative staging including CT thorax,abdomen,pelvis to assess for distal disease and magnetic resonance imaging to assess local involvement is essential.Staging radiology and MDT discussion are integral in identifying patients who require neoadjuvant radiotherapy.While Neoadjuvant radiotherapy is potentially beneficial it may also result in morbidity and thus should be reserved for those patients who are at a high risk of local failure,which includes patients with nodal involvement,extramural venous invasion and threatened circumferential margin.The aim of this review is to discuss the role of neoadjuvant radiotherapy in the management of rectal cancer.     

Colectomy is a risk factor for venous thromboembolism in ulcerative colitis

AIM: To compare venous thromboembolism(VTE) in hospitalized ulcerative colitis(UC) patients who respond to medical management to patients requiring colectomy. METHODS: Population-based surveillance from 1997 to 2009 was used to identify all adults admitted to hospital for a flare of UC and those patients who underwent colectomy. All medical charts were reviewed to confirm the diagnosis and extract clinically relevant information. UC patients were stratified by:(1) responsive to inpatient medical therapy(n = 382);(2) medically refractory requiring emergent colectomy(n = 309); and(3) elective colectomy(n = 329). The primary outcome was the development of VTE during hospitalization or within 6 mo of discharge. Heparin prophylaxis to prevent VTE was assessed. Logistic regression analysis determined the effect of disease course(i.e., responsive to medical therapy, medically refractory, and elective colectomy) on VTE after adjusting for confounders including age, sex, smoking, disease activity, comorbidities, extent of disease, and IBD medications(i.e., corticosteroids, mesalamine, azathioprine, and infliximab). Point estimates were presented as odds ratios(OR) with 95%CI.RESULTS: The prevalence of VTE among patients with UC who responded to medical therapy was 1.3% and only 16% of these patients received heparinprophylaxis. In contrast, VTE was higher among patients who underwent an emergent(8.7%) and elective(4.9%) colectomy, despite greater than 90% of patients receiving postoperative heparin prophylaxis. The most common site of VTE was intra-abdominal(45.8%) followed by lower extremity(19.6%). VTE was diagnosed after discharge from hospital in 16.7% of cases. Elective(adjusted OR = 3.69; 95%CI: 1.30-10.44) and emergent colectomy(adjusted OR = 5.28; 95%CI: 1.93-14.45) were significant risk factors for VTE as compared to medically responsive UC patients. Furthermore, the odds of a VTE significantly increased across time(adjusted OR = 1.10; 95%CI: 1.01-1.20). Age, sex, comorbidities, disease extent, disease activity, smoking, corticosteroids, mesalamine, azathioprine, and infliximab were not independently associated with the development of VTE. CONCLUSION: VTE was associated with colectomy, particularly, among UC patients who failed medical management. VTE prophylaxis may not be sufficient to prevent VTE in patients undergoing colectomy.     

Optimization of the treatment with immunosuppressants and biologics in inflammatory bowel disease

Many placebo controlled trials and meta-analyses evaluated the efficacy of different drugs for the treatment of inflammatory bowel disease(IBD),including immunosuppressants and biologics.Their use is indicated in moderate to severe disease in non responders to corticosteroids and in steroid-dependent patients,as induction and maintainance treatment.Infliximab,as well as cyclosporine,is considered a second line therapy in the case of severe ulcerative colitis,or non-responders to intravenous corticosteroids.An adequate dosage and duration of therapy with thiopurines should be reached before evaluating their efficacy.Methotrexate is a valid option in patients with Crohn’s disease but its use is confined to patients who are intolerant or non-responders to thiopurines.Evidence for the use of methotrexate in ulcerative colitis is insufficient.The use of thalidomide and mycophenolate mofetil is not recommended in patients with inflammatory bowel disease,these treatments could be considered in case of failure of all other therapeutic options.In patients with moderately active ulcerative colitis,refractory to thiopurines,the use of tacrolimus is considered an alternative to biologics.An increase of the dose or a decrease in the interval of administration of biologic treatment could be useful in the presence of an incomplete clinical response.In the case of primary failure of an anti-tumor necrosis factor alpha a switch to another one should be considered.Data on the efficacy of combination therapy are up to now insufficient to consider this strategy in all IBD patients.The final outcome of the treatment should be considered the clinical remission,with mucosa healing,and not the clinical response.The evaluation of serum concentration of thiopurine methyl transferase activity,thiopurine metabolites,biologic serum levels and antibiologic antibodies could be useful for the management of the treatment but it has not been routinely applied in clinical practice.The evidence of high risk development of lymphoma and cutaneous malignancies should be considered in patients treated with immunosuppressants and biologics for a long period.     

Factors affecting recurrence after surgery for Crohn＇s disease

Although in Crohn's disease post-operative recurrence is common, the determinants of disease recurrence remain speculative. The aim of this study was to examine factors affecting post-operative recurrence of Crohn's disease. A Medline-based literature review was carried out. The following factors were investigated: age at onset of disease, sex, family history of Crohn's disease, smoking, duration of Crohn's disease before surgery, prophylactic medical treatment (corticosteroids, 5-amino salicylic acid [5-ASA] and immunosuppressants), anatomical site of involvement, indication for surgery (perforating or non-perforating disease), length of resected bowel, anast-omotic technique, presence of granuloma in the specimen, involvement of disease at the resection margin, blood transfusions and postoperative complications. Smoking significantly increases the risk of recurrence (risk is approximately twice as high), especially in women and heavy smokers. Quitting smoking reduces the post-operative recurrence rate. A number of studies have shown a higher risk when the duration of the disease before surgery was short. There were, however, different definitions of 'short' among the studies. Prophylactic cortic-osteroids therapy is not effective in reducing the post-operative recurrence. A number of randomized controlled trials offered evidence of the efficacy of 5-ASA (mesalazine) in reducing post-operative recurrence. Recently, the thera-peutic efficacy of immunosuppressive drugs (azathioprine and 6-mercaptopurine) in the prevention of post-operative recurrence has been investigated and several studies have reported that these drugs might help prevent the recurrence. Further clinical trials would be necessary to evaluate the prophylactic efficacy of immunosuppressants. Several studies showed a higher recurrence rate in patients with perforating disease than in those with non-perforating disease. However, evidence for differing recurrence rates in perforating and non-perforating diseases is inconclusive. A number of retrospective studies reported that a stapled functional end-to-end anastomosis was associated with a lower recurrence rate compared with other types of anastomosis. However, prospective randomized studies would be necessary to draw a definite conclusion. Many studies found no difference in the recurrence rates between patients with radical resection and non-radical resection. Therefore, minimal surgery including strictureplasty has been justified in the management of Crohn's disease. In this review, the following factors do not seem to be predictive of post-operative recurrence: age at onset of disease, sex, family history of Crohn's disease, anatomical site of disease, length of resected bowel, presence of granuloma in the specimen, blood transfusions and post-operative complications. The most significant factor affecting post-operative recurrence of Crohn's disease is smoking. Smoking significantly increases the risk of recurrence. A short disease duration before surgery seems, albeit to a very minor degree, to be associated with a higher recurrence rate. 5-ASA has been shown with some degree of confidence to lead to a lower recurrence rate. The prophylactic efficacy of immunosuppressive drugs should be assessed in future. A wider anastomotic technique after resection may reduce the post-operative recurrence rate, though this should be investigated with prospective randomized controlled trials.     

Hepatitis B and immunosuppressive therapies for chronic inflammatory diseases: When and how to apply prophylaxis,with a special focus on corticosteroid therapy

Currently immunosuppressive and biological agentsare used in a more extensive and earlier way in patients with inflammatory bowel disease, rheumatic or dermatologic diseases. Although these drugs have shown a significant clinical benefit, the safety of these treatments is a challenge. Hepatitis B virus(HBV) reactivations have been reported widely, even including liver failure and death, and it represents a deep concern in these patients. Current guidelines recommend to preemptive therapy in patients with immunosuppressants in general, but preventive measures focused in patients with corticosteroids and inflammatory diseases are scarce. Screening for HBV infection should be done at diagnosis. The patients who test positive for hepatitis B surface antigen, but do not meet criteria for antiviral treatment must receive prophylaxis before undergoing immunosuppression, including corticosteroids at higher doses than prednisone 20 mg/d during more than two weeks. Tenofovir and entecavir are preferred than lamivudine because of their better resistance profile in long-term immunosuppressant treatments. There is not a strong evidence, to make a general recommendation on the necessity of prophylaxis therapy in patients with inflammatory diseases that are taking low doses of corticosteroids in short term basis or low systemic bioavailability corticosteroids such as budesonide or beclomethasone dipropionate. In these cases regularly HBV DNA monitoring is recommended, starting early antiviral therapy if DNA levels begin to rise. In patients with occult or resolved hepatitis the risk of reactivation is much lower, and excepting for Rituximab treatment, the prophylaxis is not necessary.     

Diagnosis and management of bacterial infections in decompensated cirrhosis

Bacterial infections are one of the most frequent complications in cirrhosis and result in high mortality rates.Patients with cirrhosis have altered and impaired immunity,which favours bacterial translocation.Episodes of infections are more frequent in patients with decompensated cirrhosis than those with compensated liver disease.The most common and life-threatening infection in cirrhosis is spontaneous bacterial peritonitis followed by urinary tract infections,pneumonia,endocarditis and skin and soft-tissue infections.Patients with decompensated cirrhosis have increased risk of developing sepsis,multiple organ failure and death.Risk factors associated with the development of infections are severe liver failure,variceal bleeding,low ascitic protein level and prior episodes of spontaneous bacterial peritonitis (SBP).The prognosis of these patients is closely related to a prompt and accurate diagnosis.An appropriate treatment decreases the mortality rates.Preventive strategies are the mainstay of the management of these patients.Empirical antibiotics should be started immediately following the diagnosis of SBP and the first-line antibiotic treatment is third-generation cephalosporins.However,the efficacy of currently recommended empirical antibiotic therapy is very low in nosocomial infections including SBP,compared to community-acquired episodes.This may be associated with the emergence of infections caused by Enterococcus faecium and extended-spectrum β-lactamaseproducing Enterobacteriaceae,which are resistant to the first line antimicrobial agents used for treatment.The emergence of resistant bacteria,underlines the need to restrict the use of prophylactic antibiotics to patients with the greatest risk of infections.Nosocomial infections should be treated with wide spectrum antibiotics.Further studies of early diagnosis,prevention and treatment are needed to improve the outcomes in patients with decompensated cirrhosis.     

Risk factors for immediate post-operative fatal recurrence after curative resection of hepatocellular carcinoma

AIM:To investigate the clinicopathological riskfactors for immediate post-operative fatal recurrenceof hepatocellular carcinoma (HCC),which may havepractical implication and contribute to establishinghigh risk patients for pre-or post-operative preventivemeasures against HCC recurrence.METHODS:From June 1994 to May 2004,269 patientswho received curative resection for HCC were reviewed.Of these patients,those who demonstrated diffuse intra-hepatic or multiple systemic recurrent lesions within 6mo after surgery were investigated (fatal recurrencegroup).The remaining patients were designated as thecontrol group,and the two groups were compared forclinicopathologic risk factors.RESULTS:Among the 269 patients reviewed,30patients were enrolled in the fatal recurrence group.Among the latter,20 patients showed diffuse intra-hepatic recurrence type and 10 showed multiple systemicrecurrence type.Multivariate analysis between the fatalrecurrence group and control group showed that pre-operative serum alpha-fetoprotein (AFP) level wasgreater than 1000 μg/L (P=0.02; odds ratio=2.98),tumor size greater than 6.5 cm (P=0.03; OR=2.98),and presence of microvascular invasion (P=0.01;OR=4.89) were the risk factors in the fatal recurrencegroup.The 48.1% of the patients who had all the threerisk factors and the 22% of those who had two riskfactors experienced fatal recurrence within 6 mo aftersurgery.CONCLUSION:Three distinct risk factors for immediatepost-operative fatal recurrence of HCC after curativeresection are pre-operative serum AFP level>1000 μg/L, tumor size>6.5 cm,and microvascular invasion.Thehigh risk patients with two or more risk factors should bethe candidates for various adjuvant clinical trials.     

Hepatocellular carcinoma in the post-hepatitis C virus era: Should we change the paradigm?

Hepatocellular carcinoma (HCC) is a common and deadly malignancy. The disease usually develops on a background of chronic liver disease. Until recently, the most common etiology was infection with the hepatitis C virus (HCV). The advent of direct-acting antiviral (DAA) therapies has been a major breakthrough in HCV treatment. Sustained virologic response can now be achieved in almost all treated patients, even in patients with a high risk for the development of HCC, such as the elderly or those with significant fibrosis. Early reports raised concerns of a high risk for HCC occurrence after DAA therapy both in patients with previous resection of tumors and those without previous tumors. As the World Health Organization’s goals for eradication of HCV are being endorsed worldwide, the elimination of HCV seems feasible. Simultaneous to the decrease in the burden of cirrhosis from HCV, non-alcoholic fatty liver disease (NAFLD) incidence has been increasing dramatically including significant increased incidence of cirrhosis and HCC in these patients. Surprisingly, a substantial proportion of patients with NAFLD were shown to develop HCC even in the absence of cirrhosis. Furthermore, HCC treatment and potential complications are known to be influenced by liver steatosis. These changes in etiology and epidemiology of HCC suggest the beginning of a new era: The post–HCV era. Changes may eventually undermine current practices of early detection, surveillance and management of HCC. We focused on the risk of HCC occurrence and recurrence in the post–HCV era, the surveillance needed after DAA therapy and current studies in HCC patients with NAFLD.     

Risk factors for local recurrence following neoadjuvant chemoradiotherapy for rectal cancers

Local recurrence(LR)has an adverse impact on rectal cancer treatment.Neoadjuvant chemoradiotherapy(nCRT)is increasingly administered to patients with progressive cancers to improve the prognosis.However,LR still remains a problem and its pattern can alter.Correspondingly,new risk factors have emerged in the context of nCRT in addition to the traditional risk factors in patients receiving non-neoadjuvant therapies.These risk factors are decisive when reviewing treatment options.This review aims to elucidate the distinctive risk factors related to LR of rectal cancers in patients receiving nCRT and to clarify their clinical significance.A search was conducted on PubMed to identify original studies investigating patients with rectal cancer receiving nCRT.Outcomes of interest,especially potential risk factors for LR in patients with nCRT,were then analyzed.The clinical importance of these risk factors is discussed.Remnant cancer cells,lymph-nodes and tumor response were found to be major risk factors.Remnant cancer cells decide the status of resection margins.Local excision following nCRT is promising in ypT0-1N0M0 cases.Dissection of lateral lymph nodes should be considered in advanced lowlying cancers.Although better tumor response resulted in a relatively lower recurrence rate,the evidence available is insufficient to justify a non-operative approach in clinical complete responders to nCRT.LR cannot be totally avoided by current multidisciplinary approaches.The related risk factors resulting from nCRT should be considered when making decisions regarding treatment selection.     

Criteria for the diagnosis and severity stratification of acute pancreatitis

Recent diagnostic and therapeutic progress for severe acute pancreatitis(SAP)remarkably decreased the casemortality rate.To further decrease the mortality rate of SAP,it is important to precisely evaluate the severity at an early stage,and initiate appropriate treatment as early as possible.Research Committee of Intractable Diseases of the Pancreas in Japan developed simpler criteria combining routinely available data with clinical signs.Severity can be evaluated by laboratory examinations or by clinical signs,reducing the defect values of the severity factors.Moreover,the severity criteria considered laboratory/clinical severity scores and contrastenhanced computed tomography(CE-CT)findings as independent risk factors.Thus,CE-CT scans are not necessarily required to evaluate the severity of acute pancreatitis.There was no fatal case in mild AP diagnosed by the CE-CT severity score,whereas case-mortality rate in those with SAP was 14.8%.Case-mortality of SAP that fulfilled both the laboratory/clinical and the CE-CT severity criteria was 30.8%.It is recommended,therefore,to perform CE-CT examination to clarify the prognosis in those patients who were diagnosed as SAP by laboratory/clinical severity criteria.Because the mortality rate of these patients with SAP is high,such patients should be transferred to advanced medical units.     

Managing osteoporosis in ulcerative colitis: Something new?

The authors revise the latest evidence in the literature regarding managing of osteoporosis in ulcerative colitis(UC), paying particular attention to the latest tendency of the research concerning the management of bone damage in the patient affected by UC. It is wise to assess vitamin D status in ulcerative colitis patients to recognize who is predisposed to low levels of vitamin D, whose deficiency has to be treated with oral or parenteral vitamin D supplementation. An adequate dietary calcium intake or supplementation and physical activity, if possible, should be guaranteed. Osteoporotic risk factors, such as smoking and excessive alcohol intake, must be avoided. Steroid has to be prescribed at the lowest possible dosage and for the shortest possible time. Moreover, conditions favoring falling have to been minimized, like carpets, low illumination, sedatives assumption, vitamin D deficiency. It is advisable to assess the fracture risk in all UC patient by the fracture assessment risk tool(FRAX tool), that calculates the ten years risk of fracture for the population aged from 40 to 90 years in many countries of the world. A high risk value could indicate the necessity of treatment, whereas a low risk value suggests a followup only. An intermediate risk supports the decision to prescribe bone mineral density(BMD) assessment and a subsequent patient revaluation for treatment. Dual energy X-ray absorptiometry bone densitometry can be used not only for BMD measurement, but also to collect data about bone quality by the means of trabecular bone score and hip structural analysis assessment. These two indices could represent a method of interesting perspectives in evaluating bone status in patients affected by diseases like UC, which may present an impairment of bone quality as well as of bone quantity. In literature there is no strong evidence for instituting pharmacological therapy of bone impairment in UC patients for clinical indications other than those that are also applied to the patients with osteoporosis. Therefore, a reasonable advice is to consider pharmacological treatment for osteoporosis in those UC patients who already present fragility fractures, which bring a high risk of subsequent fractures. Therapy has also to be considered in patients with a high risk of fracture even if it did not yet happen, and particularly when they had long periods of corticosteroid therapy or cumulative high dosages. In patients without fragility fractures or steroid treatment, a medical decision about treatment could be guided by the FRAX tool to determine the intervention threshold. Among drugs for osteoporosis treatment, the bisphosphonates are the most studied ones, with the best and longest evidence of efficacy and safety. Despite this, several questions are still open, such as the duration of treatment, the necessity to discontinue it, the indication of therapy in young patients, particularly in those without previous fractures. Further, it has to be mentioned that a longterm bisphosphonates use in primary osteoporosis has been associated with an increased incidence of dramatic side-effects, even if uncommon, like osteonecrosis of the jaw and atypical sub-trochanteric anddiaphyseal femoral fractures.UC is a long-lasting disease and the majority of patients is relatively young.In this scenario primary prevention of fragility fracture is the best cost-effective strategy.Vitamin D supplementation,adequate calcium intake,suitable physical activity(when possible),removing of risk factors for osteoporosis like smoking,and avoiding falling are the best medical acts.