Review of the diagnosis and management of gastrointestinal bezoars

The formation of a bezoar is a relatively infrequentdisorder that affects the gastrointestinal system.Bezoars are mainly classified into four types dependingon the material constituting the indigestible mass of thebezoar phytobezoars, trichobezoars, pharmacobezoars,and lactobezoars. Gastric bezoars often cause ulcerativelesions in the stomach and subsequent bleeding,whereas small intestinal bezoars present with smallbowel obstruction and ileus. A number of articles haveemphasized the usefulness of Coca-Cola？ administrationfor the dissolution of phytobezoars. However, persimmonphytobezoars may be resistant to such dissolutiontreatment because of their harder consistency comparedto other types of phytobezoars. Better understanding ofthe etiology and epidemiology of each type of bezoarwill facilitate prompt diagnosis and management.Here we provide an overview of the prevalence, classification,predisposing factors, and manifestations ofbezoars. Diagnosis and management strategies arealso discussed, reviewing mainly our own case series.Recent progress in basic research regarding persimmonphytobezoars is also briefly reviewed.

Chromoendoscopy of gastric adenoma using an acetic acid indigocarmine mixture

AIM: To investigate the usefulness of chromoendoscopy, using an acetic acid indigocarmine mixture (AIM), for gastric adenoma diagnosed by forceps biopsy.

Prognosis of ulcerative colitis differs between patients with complete and partial mucosal healing, which can be predicted from the platelet count

AIM: To determine the difference in clinical outcome between ulcerative colitis (UC) patients with Mayo endoscopic subscore (MES) 0 and those with MES 1.

Specific endoscopic features of ulcerative colitis complicated by cytomegalovirus infection

AIM:To identify specific colonoscopic findings in patients with ulcerative colitis (UC) complicated by cyto-megalovirus (CMV) infection.METHODS: Among UC patients who were hospitalized due to exacerbation of symptoms, colonoscopic findings were compared between 15 CMV-positive patients and 58 CMV-negative patients. CMV infection was determined by blood test for CMV antigenemia. Five aspects of mucosal changes were analyzed (loss of vascular pattern, erythema, mucosal edema, easy bleeding, and mucinous exudates) as well as five aspects of ulcerative change (wide mucosal defect, punched-out ulceration, longitudinal ulceration, irregular ulceration, and cobble-stone-like appearance). Sensitivity, specificity, positive predictive value, and negative predictive value of each finding for CMV positivity were determined.RESULTS: The sensitivity of irregular ulceration for positive CMV was 100%. The specificity of wide mucosal defect was 95%. Punched-out ulceration and lon-gitudinal ulceration exhibited relatively high sensitivity and specificity (more than 70% for each).CONCLUSION:Specific colonoscopic findings in patients with UC complicated by CMV infection were identified. These findings may facilitate the early diagnosis of CMV infection in UC patients.

Endoscopic features and prognoses of mantle cell lymphoma with gastrointestinal involvement

AIM: To evaluate the endoscopic manifestations and prognoses of gastrointestinal (GI) mantle cell lymphoma (MCL). METHODS: A database search at the Department of Pathology of Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences revealed 57 MCL patients with GI involvement. Clinical records were available for 35 of the 57 patients from 21 institutions, and those 35 patients were enrolled in this study. We summarized the gross types of endoscopic features, event-free survival (EFS), and overall survival (OS) of those patients.RESULTS: Of the 35 patients, GI involvement in the esophagus, stomach, and duodenum was found in 2 (5.7%), 26 (74.3%), and 12 (34.3%) patients, respectively. Twenty-one of the 35 patients underwent colonoscopy; among them, GI involvement in the ileum, cecum, colon, and rectum was found in 10 (47.6%), 3 (14.3%), 12 (57.1%), and 10 (47.6%), respectively. Various lesions, such as superficial, protruded, fold thickening, or ulcerative, were found in the stomach, whereas multiple lymphomatous polyposis (MLP) was dominant from the duodenum to the rectum. Twelve patients were treated with a hyper-CVAD/MA regimen, and they had better OS (3-year rate, 88.3% vs 46.4%, P < 0.01) and better EFS (3-year rate, 66.7% vs 33.8%, P < 0.05) than the remaining 23 patients who were not treated with this regimen. CONCLUSION: MLP was a representative form of intestinal involvement, whereas a variety of lesions were found in the stomach. The hyper-CVAD/MA regimen may improve survival in these patients.

Tolerability of magnifying narrow band imaging endoscopy for esophageal cancer screening

AIM:To compare the tolerability of magnifying narrow band imaging endoscopy for esophageal cancer screening with that of lugol chromoendoscopy.METHODS:We prospectively enrolled and analyzed 51 patients who were at high risk for esophageal cancer.All patients were divided into two groups:a magnifying narrow band imaging group,and a lugol chromoendoscopy group,for comparison of adverse symptoms.Esophageal cancer screening was performed on withdrawal of the endoscope.The primary endpoint was a score on a visual analogue scale for heartburn after the examination.The secondary endpoints were scale scores for retrosternal pain and dyspnea after the examinations,change in vital signs,total procedure time,and esophageal observation time.RESULTS:The scores for heartburn and retrosternal pain in the magnifying narrow band imaging group were significantly better than those in the lugol chromoendoscopy group(P =0.004,0.024,respectively,ANOVA for repeated measures).The increase in heart rate after the procedure was significantly greater in the lugol chromoendoscopy group.There was no significant difference between the two groups with respect to othervital sign.The total procedure time and esophageal observation time in the magnifying narrow band imaging group were significantly shorter than those in the lugol chromoendoscopy group(450 ± 116 vs 565 ± 174,P =0.004,44 ± 26 vs 151 ± 72,P < 0.001,respectively).CONCLUSION:Magnifying narrow band imaging endoscopy reduced the adverse symptoms compared with lugol chromoendoscopy.Narrow band imaging endoscopy is useful and suitable for esophageal cancer screening periodically.

CO_2 insufflation for potentially diffi cult colonoscopies: Effi cacy when used by less experienced colonoscopists

AIM： To clarify the effectiveness of CO2 insufflation in potentially difficult colonoscopy cases, particularly in relation to the experience level of colonoscopists. METHODS： One hundred twenty potentially difficult cases were included in this study, which involved females with a low body mass index and patients with earlier abdominal and/or pelvic open surgery or previously diagnosed left-side colon diverticulosis. Patients receiving colonoscopy examinations without sedation using a pediatric variable-stiffness colonoscope were divided into two groups based on either CO2 or standard air insuffiation. Both insufflation procedures were also evaluated according to the experience level of the respective colonoscopists who were divided into an experienced colonoscopist （EC） group and a less experienced colonoscopist （LEC） group. Study measurements included a 100-mm visual analogue scale （VAS） for patient pain during and after colonoscopy examinations, in addition to insertion to the cecum and withdrawal times. RESULTS： Examination times did not differ, however, VAS scores in the CO2 group were significantly better than in the air group （P〈 0.001, two-way ANOVA） from immediately after the procedure and up to 2 h later. There were no significant differences between either insufflation method in the EC group （P = 0.29）, however, VAS scores for CO2 insufflation were significantly better than air insufflation in the LEC group （P = 0.023） immediately after colonoscopies and up to 4 h afterwards. CONCLUSION： CO2 insufflation reduced patient pain after colonoscopy in potentially difficult cases when performed by LECs.

Control of oxidative stress in hepatocellular carcinoma: Helpful or harmful?

Oxidative stress is becoming recognized as a key factor in the progression of chronic liver disease(CLD) and hepatocarcinogenesis. The metabolically important liver is a major reservoir of mitochondria that serve as sources of reactive oxygen species, which are apparently responsible for the initiation of necroinflammation. As a result, CLD could be a major inducer of oxidative stress. Chronic hepatitis C is a powerful generator of oxidative stress, causing a high rate of hepatocarcinogenesis among patients with cirrhosis. Non-alcoholic steatohepatitis is also associated with oxidative stress although its hepatocarcinogenic potential is lower than that of chronic hepatitis C. Analyses of serum markers and histological findings have shown that hepatocellular carcinoma correlates with oxidative stress and experimental data indicate that oxidative stress increases the likelihood of developing hepatocarcinogenesis. However, the results of antioxidant therapy have not been favorable. Physiological oxidative stress is a necessary biological response, and thus adequate control of oxidative stress and a balance between oxidative and anti-oxidative responses is important. Several agents including metformin and L-carnitine can reportedly control mechanistic oxidative stress. This study reviews the importance of oxidative stress in hepatocarcinogenesis and of control strategies for the optimal survival of patients with CLD and hepatocellular carcinoma.

Long-term follow-up of ulcerative colitis patients treated on the basis of their cytomegalovirus antigen status

AIM:To clarify the impact of cytomegalovirus(CMV)activation and antiviral therapy based on CMV antigen status on the long-term clinical course of ulcerative colitis(UC)patients.METHODS:UC patients with flare-up were divided into CMV-positive and-negative groups according to the CMV antigenemia assay.The main treatment strategy provided for the patients in the CMV-positive group comprised a dose reduction of corticosteroids and administration of ganciclovir.RESULTS:The median number of days to initial remission was significantly greater for the patients in the CMV-positive group(21 d vs 16 d,P=0.009).However,the relapse rate after remission and colectomy rate during more than 30 mo of observation did not differ between the two groups.Multivariate analysis revealed that administration of ganciclovir was the only independent factor for avoiding colectomy in patients of the CMV-positive group.CONCLUSION:CMV antigen status did not significantly affect the long-term prognosis in UC patients under treatment with appropriate antiviral therapy.

Primary intestinal follicular lymphoma:How to identify follicular lymphoma by routine endoscopy

A 69-year-old Japanese female was diagnosed with primary intestinal follicular lymphoma. Esophagogas-troduodenoscopy with high-definition imaging revealed not only the typical feature of whitish polyps of up to 2 mm in diameter in the duodenal second and third portions, but also more detailed morphology, such as enlarged whitish villi and tiny whitish depositions. These findings appeared to reflect the pathological structures; infiltration of lymphoma cells into the villi were probably seen as enlargement of the villi, and the formation of lymphoid follicles were shown as opaque white spots or tiny white depositions. Thus, the above features might contribute to the distinct diagnosis of intestinal follicular lymphoma. This case indicates that routine esophagogastroduodenoscopy can visualize microsurface structures, which can be pathognomonic and help to diagnose intestinal follicular lymphoma, even without magnifying endoscopy.

Chemotherapy for advanced hepatocellular carcinoma in the sorafenib age

The kinase inhibitor sorafenib is the only systemic therapy proven to have a positive effect on survival of patients with advanced hepatocellular carcinoma(HCC).After development of sorafenib and its introduction as a therapeutic agent used in the clinic,several critical questions have been raised.Clinical parameters and biomarkers predicting sorafenib efficacy are the most important issues that need to be elucidated.Although it is difficult to know the responders in advance using conventional characteristics of patients,there are specific serum cytokines and/or gene amplification in tumor tissues that have been reported to predict efficacy of sorafenib.Risk and benefits of continuation of sorafenib beyond radiological progression is another issue to consider because no other standard therapy for advanced HCC as yet exists.In addition,effectiveness of the expanded application of sorafenib is still controversial,although a few studies have shed some light on combinational treatment with sorafenib for intermediate-stage HCC.Recently,over 50 relevant drugs have been developed and are currently under investigation.The efficacy of some of these drugs has been extensively examined,but none have demonstrated any superiority over sorafenib,so far.However,there are several drugs that have shown efficacy for treatment after sorafenib failure,and these are proceeding to further studies.To address these issues and questions,we have done extensive literature review and summarize the most current status of therapeutic application of sorafenib.

Partial stent-in-stent placement of biliary metallic stents using a short double-balloon enteroscopy

Endoscopic intervention is less invasive than percutaneous or surgical approaches and should be considered the primary drainage procedure in most cases with obstructive jaundice.Recently,therapeutic endoscopic retrograde cholangiopancreatography(ERCP) using double-balloon enteroscopy(DBE) has been shown to be feasible and effective,even in patients with surgically altered anatomies.On the other hand,endoscopic partial stent-in-stent(PSIS) placement of selfexpandable metallic stents(SEMSs) for malignant hilar biliary obstruction in conventional ERCP has also been shown to be feasible,safe and effective.We performed PSIS placement of SEMSs for malignant hilar biliary obstruction due to liver metastasis using a short DBE in a patient with Roux-en-Y anastomosis and achieved technical and clinical success.This procedure can result in quick relief from obstructive jaundice in a single session and with short-term hospitalization,even in patients with surgically altered anatomies.

Successful biliary drainage using a metal stent through the gastric stoma

We report a case of biliary drainage for malignant stricture using a metal stent with an ultrathin endoscope through the gastric stoma. A 78-year-old female was referred to our hospital for jaundice and fever. She had undergone percutaneous endoscopic gastrostomy(PEG) for esophageal obstruction after radiation therapy for cancer of the pharynx. Abdominal contrast-enhanced computed tomography showed a 3-cm enhanced mass in the middle bile duct and dilatation of the intrahepatic bile duct. We initially performed endoscopic retrograde cholangiopancreatography(ERCP) with a trans-oral approach. However, neither the side-viewing endoscope nor the ultrathin endoscope passed through the esophageal orifice. Thus, we eventually performed ERCP via the PEG stoma using an ultrathin endoscope. We performed biliary drainage with a 6F introducer selfexpanding metal stent. The cytology findings obtained by brush cytology showed malignancy. Her laboratory results were restored to normal levels after drainage and no complication occurred.

Alpha-fetoprotein before and after pegylated interferon therapy for predicting hepatocellular carcinoma development

AIM: To investigate factors that accurately predict hepatocellular carcinoma(HCC) development after antiviral therapy in chronic hepatitis C(CHC) patients. METHODS: CHC patients who received pegylated interferon and ribavirin were enrolled in this cohort study that investigated the ability of alpha-fetoprotein(AFP) to predict HCC development after interferon(IFN) therapy. RESULTS: Of 1255 patients enrolled, 665 developed sustained virological response(SVR) during mean follow-up period of 5.4 years. HCC was occurred in 89 patients, and 20 SVR patients were included. Proportional hazard models showed that HCC occurred in SVR patients showing AFP ≥ 5 ng/m L before therapy and in non-SVR patients showing AFP ≥ 5 ng/m L before and 1 year after therapy besides older age, and low platelet counts. SVR patients showing AFP ≥ 5 ng/m L before therapy and no decrease in AFP to < 5 ng/m L 1 year after therapy had significantly higher HCC incidence than non-SVR patients showing AFP ≥ 5 ng/m L before therapy and decreased AFP(P = 0.043). AFP ≥ 5 ng/m L before therapy was significantly associated with low platelet counts and high values of alanine aminotransferase(ALT) in stepwise logistic regression analysis. After age, gender, platelet count, and ALT was matched by propensity score, significantly lower HCC incidence was shown in SVR patients showing AFP < 5 ng/m L before therapy than in those showing AFP ≥ 5 ng/m L.CONCLUSION: The criteria of AFP < 5 ng/m L before and 1 year after IFN therapy is a benefical predictor for HCC development in CHC patients.

Diagnostic role of 18F-fluorodeoxyglucose positron emission tomography for follicular lymphoma with gastrointestinal involvement

AIM:To investigate the capacity for 18F-fluorodeoxyglucose(18F-FDG) positron emission tomography(PET) to evaluate patients with gastrointestinal lesions of follicular lymphoma.METHODS:This retrospective case series consisted of 41 patients with follicular lymphoma and gastrointestinal involvement who underwent 18F-FDG-PET and endoscopic evaluations at ten different institutions between November 1996 and October 2011.Data for endoscopic,radiological,and biological examinations performed were retrospectively reviewed from clinical records.A semi-quantitative analysis of 18F-FDG uptake was performed for each involved area by calculating the maximum standardized uptake value(SUVmax).Based on the positivity of 18F-FDG uptake in the gastrointestinal lesions analyzed,patients were subdivided into two groups.To identify potential predictive factors for 18F-FDG positivity,these two groups were compared with respect to gender,age at diagnosis of lymphoma,histopathological grade,pattern of follicular dendritic cells,mitotic rate,clinical stage,soluble interleukin-2 receptor levels detected by 18F-FDG-PET,lactate dehydrogenase(LDH) levels,hemoglobin levels,bone marrow involvement,detectability of gastrointestinal lesions by computed tomography(CT) scanning,and follicular lymphoma international prognostic index(FLIPI) risk.RESULTS:Involvement of follicular lymphoma in the stomach,duodenum,jejunum,ileum,cecum,colon,and rectum was identified in 1,34,6,3,2,3,and 6 patients,respectively.No patient had esophageal involvement.In total,19/41(46.3%) patients exhibited true-positive 18F-FDG uptake in the lesions present in their gastrointestinal tract.In contrast,false-negative 18F-FDG uptake was detected in 24 patients(58.5%),while false-positive 18F-FDG uptake was detected in 5 patients(12.2%).In the former case,2/19 patients had both 18F-FDG-positive lesions and 18F-FDGnegative lesions in the gastrointestinal tract.In patients with 18F-FDG avidity,the SUVmax value of the involved gastrointestinal tract ranged from 2.6 to 17.4(median:4.7).For the 18F-FDG-negative(n = 22) and-positive(n = 19) groups,there were no differences in the male to female ratios(10/12 vs 4/15,P = 0.186),patient age(63.6 ± 2.4 years vs 60.1 ± 2.6 years,P = 0.323),presence of histopathological grade 1 vs 2(20/2 and 17/2,P = 1.000),follicular dendritic cell pattern(duodenal/nodal:13/5 vs 10/3,P = 1.000),mitotic rate(low/partly high,14/1 vs 10/3,P = 0.311),clinical stage according to the Ann Arbor system(stages ⅠE and ⅡE/other,15/7 vs 15/4,P = 0.499),clinical stage according to the Lugano system(stages Ⅰ and Ⅱ-1/other,14/8 vs 14/5,P = 0.489),soluble interleukin-2 receptor levels(495 ± 78 vs 402 ± 83,P = 0.884),LDH levels(188 ± 7 vs 183 ± 8,P = 0.749),hemoglobin levels(13.5 ± 0.3 vs 12.8 ± 0.4,P = 0.197),bone marrow involvement(positive/negative,1/8 vs 1/10,P = 1.000),detectability by CT scanning(positive/negative,1/16 vs 4/13,P = 0.335),and FLIPI risk(low risk/other,16/6 vs 13/6,P = 0.763),respectively in each case.CONCLUSION:These findings indicate that it is not feasible to predict 18F-FDG-avidity.Therefore,18FFDG-PET scans represent a complementary modality for the detection of gastrointestinal involvements in follicular lymphoma patients,and surveillance of the entire gastrointestinal tract by endoscopic examinations is required.

Prediction of flare-ups of ulcerative colitis using quantitative immunochemical fecal occult blood test

AIM:To examine the feasibility of predicting the flareup of ulcerative colitis (UC) before symptoms emerge using the immunochemical fecal occult blood test (IFOBT).METHODS:We prospectively measured fecal hemoglobin concentrations in 78 UC patients using the I-FOBT every 1 or 2 mo.RESULTS:During a 20 mo-period,823 fecal samples from 78 patients were submitted.The median concentration of fecal hemoglobin was 41 ng/mL (range:0-392 500 ng/mL).There were three types of patients with regard to the correlation between I-FOBT and patient symptoms;the synchronous transition type with symptoms (44 patients),the unrelated type withsymptoms (19 patients),and the flare-up predictive type (15 patients).In patients with the flare-up predictive type,the values of I-FOBT were generally low during the study period with stable symptoms.Two to four weeks before the flare-up of symptoms,the I-FOBT values were high.Thus,in these patients,I-FOBT could predict the flare-up before symptoms emerged.CONCLUSION:Flare-up could be predicted by I-FOBT in approximately 20% of UC patients.These results warrant periodical I-FOBT in UC patients.

Dilation of a severe bilioenteric or pancreatoenteric anastomotic stricture using a Soehendra Stent Retriever

Bilioenteric or pancreatoenteric anastomotic stric-tures often occur after surgery for a pancreaticobiliary disorder. Therapeutic endoscopic retrograde cholan-giopancreatography using balloon enteroscopy has been shown to be feasible and effective in patients with such strictures. However, when a benign anas-tomotic stricture is severe, a dilation catheter cannot pass through the stricture despite successful insertion of the guidewire. We report on the usefulness of the Soehendra Stent Retriever over a guidewire for dilating a severe bilioenteric or pancreatoenteric anastomotic stricture under short double-balloon enteroscopy, in two patients with surgically altered anatomies.

Endoscopic hemostasis for hemorrhage from an ileal diverticulum

Hemorrhage from a non-Meckelian jejunoileal diverticulum is rare, and it is generally difficult to diagnose the source of the bleeding. Here, we report the case of a 59- year-old male with hemorrhage from an ileal diverticulum. Contrast computed tomography scans demonstrated the ileal diverticulum and extravasation of the contrast medium around it. The diagnosis was then made by computed tomography scans, and endoscopic mechanical hemostasis was performed under colonoscopy with three metal clips. The management of hemorrhage from jejunoileal diverticula is discussed.

Proton pump inhibitor step-down therapy for GERD:A multi-center study in Japan

AIM:To investigate the predictors of success in stepdown of proton pump inhibitor and to assess the quality of life(QOL).METHODS:Patients who had heartburn twice a week or more were treated with 20 mg omeprazole(OPZ) once daily for 8 wk as an initial therapy(study 1).Patients whose heartburn decreased to once a week or less at the end of the initial therapy were enrolled in study 2 and treated with 10 mg OPZ as maintenance therapy for an additional 6 mo(study 2).QOL was in-vestigated using the gastrointestinal symptom rating scale(GSRS)before initial therapy,after both 4 and 8 wk of initial therapy,and at 1,2,3,and 6 mo after starting maintenance therapy.RESULTS:In study 1,108 patients were analyzed.Their characteristics were as follows;median age:63(range: 20-88)years,sex:46 women and 62 men.The success rate of the initial therapy was 76%.In the patients with successful initial therapy,abdominal pain,indigestion and reflux GSRS scores were improved.In study 2,83 patients were analyzed.Seventy of 83 patients completed the study 2 protocol.In the per-protocol analysis,80%of 70 patients were successful for stepdown.On multivariate analysis of baseline demographic data and clinical information,no previous treatment for gastroesophageal reflux disease(GERD)[odds ratio (OR)0.255,95%CI:0.06-0.98]and a lower indigestion score in GSRS at the beginning of step-down therapy(OR 0.214,95%CI:0.06-0.73)were found to be the predictors of successful step-down therapy.The improved GSRS scores by initial therapy were maintained through the step-down therapy.CONCLUSION:OPZ was effective for most GERD patients.However,those who have had previous treatment for GERD and experience dyspepsia before stepdown require particular monitoring for relapse.

Disparity in clinical care for patients with inflammatory bowel disease between specialists and non-specialists

Background: Although inflammatory bowel disease (IBD) patients have been increasing and new thera-peutic options for IBD have been developed, there are relatively few clinicians who specialize in IBD. Patients treated by a non-specialist of IBD may not receive appropriate treatment. This study aimed to compare disease and medication status between IBD patients treated by a specialist and those treated by a non-specialist. Methods: Medical charts of ambulating IBD patients in two hospitals were examined. All patients in one hospital were treated by one of the IBD specialists, while in the other hospital, patients were treated by one of the gastroenterologists who was a non-specialist of IBD. Results: The numbers of IBD patients were 255 (hospital with specialists) and 74 (hospital without specialists), respectively. Disease activity of the patients was not well-controlled in the hospital without specialists compared to in the hospi- tal with specialists (ulcerative colitis (UC): p = 0.0006 and Crohn’s disease: p = 0.012, respectively). The proportion of UC patients who received an insufficient dose of mesalazine (Pentasa < 3 g/day or Asacol < 3.6 g/day) was higher in the hospital without specialists (47% vs. 15%, p < 0.0001). In the hospital without specialists, more patients received long-term corticosteroids (UC: 23% vs. 5%, p < 0.0001), while fewer patients received immunomodulators (UC: 8% vs. 46%, p < 0.0001). Conclusions: IBD patients of the hospital without specialists were not well-controlled and were not prescribed appropriately with thera-peutic drugs. Fostering and placement of the specialist of IBD is an urgent problem.