Review of dynamic contrast-enhanced ultrasound guidance in ablation therapy for hepatocellular carcinoma

Local ablative techniques-percutaneous ethanol injection, microwave coagulation therapy and radiofrequency ablation (RFA)-have been developed to treat unresectable hepatocellular carcinoma (HCC). The success rate of percutaneous ablation therapy for HCC depends on correct targeting of the tumor via an imaging technique. However, probe insertion often is not completely accurate for small HCC nodules, which are poorly def ined on conventional B-mode ultrasound (US) alone. Thus, multiple sessions of ablation therapy are frequently required in diffi cult cases. By means of two breakthroughs in US technology, harmonic imaging and the development of second-generation contrast agents, dynamic contrast-enhanced harmonic US imaging with an intravenous contrast agent can depict tumor vascularity sensitively and accurately, and is able to evaluate small hypervascular HCCs even when B-mode US cannot adequately characterize the tumors. Therefore, dynamic contrast-enhanced US can facilitate RFA electrode placement in hypervascular HCC, which is poorly depicted by B-mode US. The use of dynamic contrast-enhanced US guidance in ablation therapy for liver cancer is an effi cient approach. Here, we present an overview of the current status of dynamic contrast-enhanced US-guided ablation therapy, and summarize the current indications and outcomes of reported clinical use in comparison with that of other modalities.

Evidence based review of the impact of image enhanced endoscopy in the diagnosis of gastric disorders

Gastric cancer is the third most common cause of cancer-related death.Advanced stages of gastric cancersgenerally have grim prognosis.But,good prognosis can be achieved if such cancers are detected,diagnosed and resected at early stages.However,early gastric cancers and its precursors often produce only subtle mucosal changes and therefore quite commonly remain elusive at the conventional examination with white light endoscopy.Image-enhanced endoscopy makes mucosal lesions more conspicuous and can therefore potentially yield earlier and more accurate diagnoses.Recent years have seen growing work of research in support of various types of image enhanced endoscopy(IEE) techniques(e.g.,dye-chromoendoscopy;magnification endoscopy;narrow-band imaging;flexible spectral imaging color enhancement;and I-SCAN) for a variety of gastric pathologies.In this review,we will examine the evidence for the utilization of various IEE techniques in the diagnosis of gastric disorders.

Impact of liver steatosis on response to pegylated interferon therapy in patients with chronic hepatitis B

AIM： To evaluate the impact of liver steatosis upon response to given therapy in chronic hepatitis B （CriB） patients.METHODS： 84 consecutive Crib patients treated with 48-wk PEGylated interferon （PEG-IFN） therapy were enrolled. Baseline characteristics and sustained viral re- sponse （SVR） to PEG-IFN therapy were evaluated.RESULTS： Mean body mass index （BMI） was 27.36 ±4.4 kg/m2. Six （7.1%） had hypertension and three （3.5%） had diabetes mellitus. Steatosis was present in 22.6% （19/84） of liver biopsy samples. Age, BMI, and triglyceride levels of the patients with hepatic steatosis were significantly higher than those without hepatic steatosis （P 〈 0.05）. SVR to PEG-IFN therapy was 21.4% （18/84）. Sixteen of these 18 CriB patients with SVR （88.9%） did not have any histopathologically determined steatosis. On the other hand, only two of the 19 CriB patients with hepatic steatosis had SVR （10.5%）. Although the SVR rate observed in patients without steatosis （16/65, 24.6%） was higher compared to those with steatosis （2/19, 10.5%）, the difference was not statistically significant （P 〉 0.05）.CONCLUSION： Occurrence of hepatic steatosis is significantly high in CHB patients and this association leads to a trend of decreased, but statistically insignificant, SVR rates to PEG-IFN treatment,

Etiopathogenesis of primary sclerosing cholangitis

Primary sclerosing cholangitis(PSC) is a chronic cholestatic liver disease of unknown etiology but lymphocytic portal tract infiltration is suggestive of an immune-mediated basis for this disease.Associations with inflammatory bowel disease(IBD) especially ulcerative colitis(UC),and with particular autoimmune diseases,as well as the genetic associations further suggest PSC may be an immune-mediated disease.The immunogenetics of PSC have been the subject of active research and several HLA and non-HLA associated genes have been implicated in the development of the disease.Lymphocytes derived from the inflamed gut may enter the liver via the enterohepatic circulation to cause hepatic disease.PSC may be triggered in genetically susceptible individuals by infections or toxins entering the portal circulation through a permeable colon and hence evoking an abnormal immune response.

Narrow-band imaging endoscopy with and without magnification in diagnosis of colorectal neoplasia

AIM:To evaluate the diagnostic efficacies of narrowband imaging(NBI) endoscopy with and without high magnification in distinguishing neoplasia from nonneoplasia colorectal lesions.METHODS:A total of 118 patients with 123 colorectal lesions examined by NBI endoscopy in the Zhejiang Provincial People's Hospital from September 2008 to April 2010 were enrolled in this study.These lesions were classified by pit pattern and capillary pattern,and then assessed by histopathology.RESULTS:Ten lesions not meeting the diagnostic criteria were excuded,the overall diagnostic accuracy of NBI endoscopy in distinguishing neoplasia from non-neoplasia colorectal lesions was 91.2%(103/113),and that of NBI endoscopy with and without high magnification was 93.0%(40/43) and 90.0%(63/70),respectively.Both were significantly higher than that of conventional colonoscopy reported in the literature(P < 0.05),but there was no significant difference between the two groups(P > 0.05).CONCLUSION:Besides NBI magnifying endoscopy,NBI endoscopy without magnification may also be used to distinguish neoplasia from non-neoplasia colorectal lesions.

Features of hepatocellular carcinoma in cases with autoimmune hepatitis and primary biliary cirrhosis

AIM: To characterize the clinical features of hepatocellular carcinoma (HCC) associated with autoimmune liver disease, we critically evaluated the literature on HCC associated with autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC). METHODS: A systematic review of the literature was conducted using the Japana Centra Revuo Medicina database which produced 38 cases of HCC with AIH (AIH-series) and 50 cases of HCC with PBC (PBC-series). We compared the clinical features of these two sets of patients with the general Japanese HCC population. RESULTS: On average, HCC was more common in men than in women with AIH or PBC. While many patients underwent chemolipiodolization (CL) or transcatheter arterial embolization (TAE) (AIH-series: P = 0.048 (vs operation), P = 0.018 (vs RFA, PEIT); PBC-series: P = 0.027 (vs RFA, PEIT), others refused therapeutic interventions [AIH-series: P = 0.038 (vs RFA, PEIT); PBC-series: P = 0.003 (vs RFA, PEIT)].Liver failure was the primary cause of death among patients in this study, followed by tumor rupture. The survival interval between diagnosis and death was fairly short, averaging 14 ± 12 mo in AIH patients and 8.4 ± 14 mo in PBC patients. CONCLUSION: We demonstrated common clinical features among Japanese cases of HCC arising from AIH and PBC.

A clinical trial of combined use of rosiglitazone and 5-aminosalicylate for ulcerative colitis

AIM: To investigate the therapeutic effects of the combined use of rosiglitazone and aminosalicylate on mild or moderately active ulcerative colitis (UC).METHODS: According to the national guideline for diagnosis and treatment of inflammatory bowel disease (IBD) in China, patients with mild or moderately active UC in our hospital were selected from July to November, 2004. Patients with infectious colitis, amoebiasis, or cardiac, renal or hepatic failure and those who had received corticosteroid or immunosuppressant treatment within the last month were excluded. Following a quasi-randomization principle, patients were allocated alternatively into the treatment group (TG) with rosiglitazone 4 mg/d plus 5-ASA 2 g/d daily or the control group (CG) with 5-ASA 2 g/d alone, respectively, for 4 wk. Clinical changes were evaluated by Mayo scoring system and histological changes by Truelove-Richards' grading system at initial and final point of treatment.RESULTS: Forty-two patients completed the trial, 21 each in TG and CG. The Mayo scores in TG at initial and final points were 5.87 (range: 4.29-7.43) and 1.86 (range: 1.03-2.69) and those in CG were 6.05 (range: 4.97-7.13) and 2.57 (range: 1.92-3.22) respectively. The decrements of Mayo scores were 4.01 in TG and 3.48 in CG, with a remission rate of 71.4% in TG and 57.1% in CG, respectively. Along with the improvement of disease activity index (DAI), the histological grade improvement was more significant in TG than in CG (P < 0.05).CONCLUSION: Combined treatment with rosiglitazone and 5-ASA achieved better therapeutic effect than 5-ASA alone without any side effects. Rosiglitazone can alleviate colonic inflammation which hopefully becomes a novel agent for UC treatment.

Hepatitis C: Treatment of difficult to treat patients

Over the past several years, more so recently, treatment options for hepatitis C virus(HCV) have seemed to exponentially grow. Up until recently, the regimen of pegylated interferon(peg-IFN) and ribavirin(RBV) stood as the standard of care. Direct acting antivirals, which target nonstructural proteins involved in replication and infection of HCV were first approved in 2011 as an addition to the peg-IFN and RBV regimen and with them have come increased sustained virological response rates(SVR). The previously reported 50%-70% SVR rates using the combination of peg-IFN and RBV are no longer the standard of care with direct acting antiviral(DAA) based regimens now achieving SVR of 70%-90%. PegIFN free as well as "all oral" regimens are also available. The current randomized controlled trials available show favorable SVRs in patients who are naive to treatment, non-cirrhotic, and not human immunodeficiency virus(HIV)-co-infected. What about patients who do not fit into these categories? In this review, we aim to discuss the currently approved and soon to be approved DAAs while focusing on their roles in patients that are treatment experienced, cirrhotic, or co-infected with HIV. In this discussion, review of the clinical trials leading to recent consensus guidelines as well as discussion of barriers to treatment will occur. A case will attempt will be made that social services, including financial support and drug/alcohol treatment, should be provided to all HCV infected patients to improve chances of cure and thus prevention of late stage sequela.

Association of human leukocyte antigen DQB1 and DRB1 alleles with chronic hepatitis B

AIM: To investigate the effect of human leukocyte antigen (HLA) DRB1 and DQB1 alleles on the inactive and advanced stages of chronic hepatitis B.

A unique case of collagenous colitis presenting as protein-losing enteropathy successfully treated with prednisolone

A 76-year-old woman with a 5-mo history of recurrent diarrhea and generalized edema was admitted to our hospital. Colonoscopy revealed edematous mucosa,and histopathological examination was compatible with collagenous colitis. Protein leakage from the colon,particularly in the ascending portion,was identified on 99mTc-human serum albumin scintigraphy. Collagenous colitis associated with protein-losing enteropathy (PLE) without small bowel disease was diagnosed. Prednisolone treatment ameliorated diarrhea and hypoproteinemia. Collagenous colitis should be included in the differential diagnosis of chronic diarrhea with hypoproteinemia for appropriate management.

Value of acoustic radiation force impulse elastography for the assessment of ascites syndrome

AIM:To assess the feasibility of performing acoustic radiation force impulse(ARFI) elastography in patients with ascites and its predictive value for the cirrhotic or non-cirrhotic etiology of ascites.METHODS:Our study included 153 patients with ascites,mean age 58.8 ± 13.1 years.One hundred and fifteen(75.2%) patients had ascites in the context of cirrhosis,29(18.9%) had non-cirrhotic ascites(diagnosed by clinical,ultrasound,endoscopic and/or laparoscopic criteria) and in 9(5.9%) cases we could not establish the etiology of ascites.We performed 10 ARFI measurements and the median value was calculated and expressed in meters/second(m/s).Among the 29 patients with non-cirrhotic ascites were included:20 laparoscopically demonstrated peritoneal carcinomatosis with histological confirmation,7 acute pancreatitis with ascites which later resolved,and one case each of lymphatic ascites and ascites in the context of a liver abscess.In 11 of the 20 patients with peritoneal carcinomatosis,the liver structure was homogenous in the ultrasound examination and in 9 patients the ultrasound exam revealed liver metastases.RESULTS:We could not obtain valid ARFI measurements in 5 patients(3.2%).The mean liver stiffness measurements by means of ARFI were statistically significantly higher in patients with cirrhotic ascites than in those with non-cirrhotic ascites:3.04 ± 0.70 vs 1.45 ± 0.59 m/s(P < 0.001).For a cut-off value of 1.8 m/s for predicting cirrhosis(and ascites in the context of cirrhosis),as obtained in a previous study,ARFI had 98.1% sensitivity,86.2% specificity,96.4% positive predictive value,92.5% negative predictive value and 95.6% accuracy for predicting cirrhotic ascites.For a cut-off value of 1.9 m/s the accuracy was 94.9% and for a 2 m/s cut-off value it was 92.8%.CONCLUSION:ARFI elastography is feasible in most patients with ascites and has a very good predictive value for the cirrhotic or non-cirrhotic etiology of ascites.

Epidemiology of inflammatory bowel disease in racial and ethnic migrant groups

AIM To summarise the current literature and define patterns of disease in migrant and racial groups.METHODS A structured key word search in Ovid Medline and EMBASE was undertaken in accordance with PRISMA guidelines. Studies on incidence, prevalence and disease phenotype of migrants and races compared with indigenous groups were eligible for inclusion. RESULTS Thirty-three studies met the inclusion criteria. Individual studies showed significant differences in incidence, prevalence and disease phenotype between migrants or race and indigenous groups. Pooled analysis could only be undertaken for incidence studies on South Asians where there was significant heterogeneity between the studies [95% for ulcerative colitis(UC), 83% for Crohn's disease(CD)]. The difference between incidence rates was not significant with a rate ratio South Asian: Caucasian of 0.78(95%CI: 0.22-2.78) for CD and 1.39(95%CI: 0.84-2.32) for UC. South Asians showed consistently higher incidence and more extensive UC than the indigenous population in five countries. A similar pattern was observed for Hispanics in the United States. Bangladeshis and African Americans showed an increased risk of CD with perianal disease. CONCLUSION This review suggests that migration and race influence the risk of developing inflammatory bowel disease. This may be due to different inherent responses upon exposure to an environmental trigger in the adopted country. Further prospective studies on homogenous migrant populations are needed to validate these observations, with a parallel arm for in-depth investigation of putative drivers.

Robot-assisted surgery for gastric cancer

Minimally invasive surgery for gastric cancer is a rela-tively new research field, with convincing results mostly stemming from Asian countries. The use of the robotic surgery platform, thus far assessed as a safe procedure, which is also easier to learn, sets the background for a wider spread of minimally invasive technique in the treatment of gastric cancer. This review will cover the literature published so far, analyzing the pros and cons of robotic surgery and highlighting the remaining study questions.

Evaluation of mannitol effect in patients with acute hepatic failure and acute-on-chronic liver failure using conventional MRI,diffusion tensor imaging and in-vivo proton MR spectroscopy

AIM： To evaluate the effect of an intravenous bolus of mannitol in altering brain metabolites, brain water content, brain parenchyma volume, cerebrospinal fluid （CSF） volume and clinical signs in controls and in patients with acute liver failure （ALF） and acute- on-chronic liver failure （ACLF）, by comparing changes in conventional magnetic resonance imaging （MRI）, in vivo proton magnetic resonance spectroscopy （PMRS） and diffusion tensor imaging （DTI） before and after its infusion.METHODS： Five patients each with ALF and ACLF in grade 3 or 4 hepatic encephalopathy and with clinical signs of raised intracranial pressure were studied along with five healthy volunteers. After baseline MRI, an intravenous bolus of 20% mannitol solution was given over 10 min in controls as well as in patients with ALF and ACLE Repeat MRI for the same position was acquired 30 rnin after completing the rnannitol injection. RESULTS： No statistically significant difference was observed between controls and patients with ALF and ACLF in metabolite ratios, DTI metrics and brain volume or CSF volume following 45 rain of mannitol infusion. There was no change in clinical status at the end of post-mannitol imaging. CONCLUSION： The osmotic effect of mannitol did not result in significant reduction of brain water content, alteration in metabolite ratios or any change in the clinical status of these patients during or within 45 min of mannitol infusion.

Management of gastric mucosa-associated lymphoid tissue lymphoma in patients with extra copies of the MALT1 gene

AIM To identify the clinical features of gastric mucosaassociated lymphoid tissue(MALT) lymphoma with extra copies of MALT1.METHODS This is a multi-centered,retrospective study. We reviewed 146 patients with MALT lymphoma in the stomach who underwent fluorescence in situ hybridization analysis for t(11;18) translocation. Patients were subdivided into patients without t(11;18) translocation or extra copies of MALT1(Group A,n = 88),patients with t(11;18) translocation(Group B,n = 27),and patients with extra copies of MALT1(Group C,n = 31). The clinical background,treatment,and outcomes of each group were investigated.RESULTS Groups A and C showed slight female predominance,whereas Group B showed slight male predominance. Mean ages and clinical stages at lymphoma diagnosis were not different between groups. Complete response was obtained in 61 patients in Group A(69.3%),22 in Group B(81.5%),and 21 in Group C(67.7%). Helicobacter pylori(H. pylori) eradication alone resulted in complete remission in 44 patients in Group A and 13 in Group C. In Group B,14 patients underwent radiotherapy alone,which resulted in lymphoma disappearance. Although the difference was not statistically significant,event-free survival in Group C tended to be inferior to that in Group A(P = 0.10).CONCLUSION Patients with t(11;18) translocation should be treated differently from others. Patients with extra copies of MALT1 could be initially treated with H. pylori eradication,similar to patients without t(11;18) translocation or extra copies of MALT1.

Prevalence of microscopic colitis in patients with diarrhea of unknown etiology in Turkey

AIM: To investigate the prevalence and demography of microscopic colitis in patients with diarrhea of unknown etiology and normal colonoscopy in Turkey. METHODS: Between March, 1998 to July, 2005, 129 patients with chronic non-bloody diarrhea of unexplained etiology who had undergone full colonoscopy with no obvious abnormalities were included in the study. Two biopsies were obtained from all colonic segments and terminal ileum for diagnosis of microscopic colitis. On histopathologic examination, criteria for lymphocytic colitis (intraepithelial lymphocyte ≥ 20 per 100 intercryptal epithelial cells, change in surface epithelium, mononuclear infiltration of the lamina propria) and collagenous colitis (subepithelial collagen band thickness ≥ 10 μm) were explored. RESULTS: Lymphocytic colitis was diagnosed in 12 (9%) patients (Female/Male: 7/5, mean age: 45 year, range: 27-63) and collagenous colitis was diagnosed in only 3 (2.5%) patients (all female, mean age: 60 years, range: 54-65).CONCLUSION: Biopsy of Turkish patients with the diagnosis of chronic non-bloody diarrhea of unexplained etiology and normal colonoscopic findings will reveal microscopic colitis in approximately 10% of the patients. Lymphocytic colitis is 4 times more frequent than collagenous colitis in these patients.

Alcoholic hepatitis: The pivotal role of Kupffer cells

Kupffer cells play a central role in the pathogenesis of alcoholic hepatitis(AH). It is believed that alcohol increases the gut permeability that results in raised levels of serum endotoxins containing lipopolysaccharides(LPS). LPS binds to LPS-binding proteins and presents it to a membrane glycoprotein called CD14, which then activates Kupffer cells via a receptor called tolllike receptor 4. This endotoxin mediated activation of Kupffer cells plays an important role in the inflammatory process resulting in alcoholic hepatitis. There is no effective treatment for AH, although notable progress has been made over the last decade in understanding the underlying mechanism of alcoholic hepatitis. We specifically review the current research on the role of Kupffer cells in the pathogenesis of AH and the treatment strategies. We suggest that the imbalance between the pro-inflammatory and the anti-inflammatory process as well as the increased production of reactive oxygen species eventually lead to hepatocyte injury, the final event of alcoholic hepatitis.

Endoscopic approach to the diagnosis of pancreatic cystic tumor

Because of the aging of the population,prevalence of medical checkups,and advances in imaging studies,the number of pancreatic cystic lesions detected has increased. Once these lesions are detected,neoplastic cysts should be differentiated from non-neoplastic cysts. Furthermore,because of the malignant potential of some neoplastic pancreatic cysts,further differentiation between benign and malignant cysts should be made regardless of their size. Although endoscopic ultrasound(EUS) has a very high diagnostic performance for pancreatic cystic lesions among the various imaging modalities,EUS findings alone are insufficient for the differentiation of pancreatic cysts and diagnosis of malignancy. In addition,cytology by EUS-guided fine-needle aspiration(FNA) has a high specificity but a low sensitivity for diagnosing malignancy in pancreatic cystic tumors. The levels of amylase,lipase,and tumor markers in pancreatic cystic fluid are considered auxiliary parameters for diagnosis of benign and malignant cysts,and a definitive diagnosis of malignancy using these parameters is difficult. Thus,in addition to EUS,cytology by EUS-FNA,and cystic fluid analysis,new techniques based on EUS-guided through-the-needle imaging,such as confocal laser endomicroscopy and cystoscopy,have been explored in recent years.

Does deep sedation with propofol affect adenoma detection rates in average risk screening colonoscopy exams?

To determine the effect of sedation with propofol on adenoma detection rate (ADR) and cecal intubation rates (CIR) in average risk screening colonoscopies compared to moderate sedation. METHODSWe conducted a retrospective chart review of 2604 first-time average risk screening colonoscopies performed at MD Anderson Cancer Center from 2010-2013. ADR and CIR were calculated in each sedation group. Multivariable regression analysis was performed to adjust for potential confounders of age and body mass index (BMI). RESULTSOne-third of the exams were done with propofol (n = 874). Overall ADR in the propofol group was significantly higher than moderate sedation (46.3% vs 41.2%, P = 0.01). After adjustment for age and BMI differences, ADR was similar between the groups. CIR was 99% for all exams. The mean cecal insertion time was shorter among propofol patients (6.9 min vs 8.2 min; P < 0.0001). CONCLUSIONDeep sedation with propofol for screening colonoscopy did not significantly improve ADR or CIR in our population of average risk patients. While propofol may allow for safer sedation in certain patients (e.g., with sleep apnea), the overall effect on colonoscopy quality metrics is not significant. Given its increased cost, propofol should be used judiciously and without the implicit expectation of a higher quality screening exam.

Diagnostic yield of third eye retroscope on adenoma detection during colonoscopy:A systematic review and meta-analysis

AIM： To determine the diagnostic yield of the “third eye retroscope”, on adenoma detection rate during screening colonoscopy.METHODS： The “third eye retroscope” when used with standard colonoscopy provides an additional retro-grade view to visualize lesions on the proximal aspects of folds and fexures. We searched MEDLINE （PubMed and Ovid）, SCOPUS （including MEDLINE and EMBASE databases）, Cochrane Database of Systemic Reviews, Google Scholar, and CINAHL Plus databases to identify studies that evaluated diagnostic yield of “third eye retroscope” during screening colonoscopy. DerSimonian Laird random effects model was used to generate the overall effect for each outcome. We evaluated statistical heterogeneity among the studies by using the Cochran Q statistic and quantifed by I2 statistics.RESULTS： Four distinct studies with a total of 920 pa-tients, mean age 59.83 （95%CI： 56.77-62.83） years, were included in the review. The additional adenoma detection rate （AADR） defined as the number of ad-ditional adenomas identified due to “third eye retro-scope” device in comparison to standard colonoscopy alone was 19.9% （95%CI： 7.3-43.9）. AADR for right and left colon were 13.9% （95%CI： 9.4-20） and 10.7 （95%CI： 1.9-42）, respectively. AADR for polyps ≥ 6 mm and ≥ 10 mm were 24.6% （95%CI： 16.6-34.9） and 24.2% （95%CI： 12.9-40.8）, respectively. The ad-ditional polyp detection rate defined as the number of additional polyps identifed due to “third eye retro-scope” device in comparison to standard colonoscopyalone was 19.8% （95%CI： 7.9-41.8）. There were no complications reported with use of “third eye retro-scope” device.CONCLUSION： The “third eye retroscope” device when used with standard colonoscopy is safe and de-tects 19.9% additional adenomas, compared to stan-dard colonoscopy alone.