Enzyme-linked immunosorbent assay of 3 Screen Islet Cell Autoantibody in patients with autoimmune thyroid disease

BACKGROUND In recent years,the emergence of multiplex technology that can simultaneously measure multiple anti-islet autoantibodies has become particularly valuable for the staging and early diagnosis of immune-mediated type 1 diabetes(T1D).While it has been established that 20%-30%of T1D patients suffer from autoimmune thyroid disease(AITD),there is limited available data regarding the presence of anti-islet autoantibodies in AITD patients.Among commercially available anti-islet autoantibodies,glutamic acid decarboxylase 65 autoantibodies(GADAs)are often the first marker measured in general clinical practice.AIM To investigate the frequency of anti-islet autoantibodies in AITD patients.METHODS Our study involved four hundred ninety-five AITD patients,categorized into three distinct groups:AITD with T1D(n=18),AITD with phenotypic type 2 diabetes(T2D)(n=81),and AITD without diabetes(n=396),and the enzyme-linked immunosorbent assay(ELISA)was employed to determine the frequencies of 3 Screen Islet Cell Autoantibody(3 Screen ICA),GADA,insulinoma-associated antigen-2 autoantibodies(IA-2As),and zinc transporter 8 autoantibodies(ZnT8As)within these groups.RESULTS The frequency of 3 Screen ICA in AITD patients with T1D,T2D,and those without diabetes were 88.9%,6.2%,and 5.1%,respectively,with no significant difference seen between the latter two groups.Notably,the frequency of 3 Screen ICA was 11.1%higher in AITD patients with T1D,1.3%higher in AITD patients with T2D,and 1.1%higher in AITD patients without diabetes compared to GADA,respectively.Furthermore,12.5%,20.0%,and 20.0%of the 3 Screen ICA-positive patients were negative for GADA.Additionally,1.3%of the AITD patients who tested negative for 3 Screen ICA in both the AITD with T2D and non-diabetic AITD groups were found to be positive for individual autoantibodies.Among the 3 Screen ICA-positive patients,there was a significantly higher proportion of individuals with multiple autoantibodies in AITD patients with T1D compared to those without diabetes(37.5%vs 5.0%,P<0.05).However,this proportion was similar to that in AITD patients with T2D(20.0%).Nevertheless,there was no significant difference in 3 Screen ICA titers between AITD patients with T1D and those without diabetes(436.8±66.4 vs 308.1±66.4 index).Additionally,no significant difference in 3 Screen ICA titers was observed between Graves’disease and Hashimoto’s thyroiditis in any of the groups.CONCLUSION Our findings reveal that some AITD patients without diabetes exhibit 3 Screen ICA titers comparable to those in AITD patients with T1D.Thus,3 Screen ICA outperforms GADA in identifying latent anti-islet autoantibody-positive individuals among AITD patients.

Drug-induced sarcoidosis-like reaction three months after BNT162b2 mRNA COVID-19 vaccination:A case report and review of literature

BACKGROUND A 70-year-old man with hepatitis C virus-related recurrent hepatocellular carcinoma was admitted for further diagnosis of a 1 cm iso-hyperechoic nodule in segment(S)5.CASE SUMMARY Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging(EOB-MRI)revealed the nodule in S5 with a defect at the hepatobiliary phase,hyperintensity on diffusion weighted imaging(DWI)and hypointensity on apparent diffusion coefficient(ADC)map.Contrast-enhanced computed tomography revealed hypervascularity at the early phase,and delayed contrast-enhancement was observed at the late phase.Contrast-enhanced ultrasound(US)revealed incomplete defect at the late vascular phase.Inflammatory liver tumor,lymphoproliferative disease,intrahepatic cholangiocarcinoma(small duct type)and bile duct adenoma were suspected through the imaging studies.US guided biopsy,however,showed a noncaseating hepatic sarcoid-like epithelioid granuloma(HSEG),and histopathological analysis disclosed spindle shaped epithelioid cells harboring Langhans-type multinucleated giant cells.One month after admission,EOB-MRI signaled the disappearance of the defect at the hepatobiliary phase,of hyperintensity on DWI,of hypointensity on ADC map,and no stain at the early phase.CONCLUSION That the patient had received BNT162b2 messenger RNA(mRNA)coronavirus disease 2019 vaccination 3 mo before the occurrence of HSEG,and that its disappearance was confirmed 4 mo after mRNA vaccination suggested that the drug-induced sarcoidosis-like reaction(DISR)might be induced by the mRNA vaccination.Fortunately,rechallenge of drug-induced DISR with the third mRNA vaccination was not confirmed.

Long-Term Active and Passive Horticultural Therapy Intervention for Elderly Patients with Moderate Dementia and AI Analysis of Medical Records and Care Documents

Background: Previous studies have shown that Hand Care Treatment, a form of passive horticultural therapy, is effective in preventing dementia and MCI and reducing the rate of progression. Due to the Covid-19 pandemic, various activity restrictions were implemented in Japan from March 2020, and the number of elderly people without care and rehabilitation will the number of elderly people without care and rehabilitation has been increasing. Purpose: Progression of cognitive, physical, and mental disability was examined for long-term horticultural therapy study subjects by level of care required. Methods: One subject who had been diagnosed with dementia and was residing in an elderly care facility and consented to a long-term study was selected. In addition to assessments using various evaluation forms, data recorded from time to time, including changes in care plans, were analyzed using text mining methods. Results: This subject tended to progress slowly from 1 to 2 care needs, but progressed from 3 to 5 care needs over a 2-year period. The results of the assessment chart test showed that cognitive impairment and IADL decreased with each increase in the level of care required, but DBD remained the same at the time of admission, even at 5 years of care required. A comparison of HCT and aroma intervention with and without aroma intervention during the nursing care level 1 showed that the improvement in physical, mental, and cognitive function was expected to be higher at the time of intervention. Text-mining inspections have revealed that during the period of nursing care level 1 - 5, active horticultural therapy techniques, and passive horticultural therapy techniques such as HCT and brain rejuvenation aromatherapy were found to betweenness centrality with each other. Conclusion: From the results of mean score of DBD, although the nursing care level has progressed from 1 to a maximum of 5, it can be concluded that the burden of care has not become heavier. There was no tendency for the progression of cognitive impairment in this subject to be faster than in the general AD population, despite the influences of Covid-19. The results indicated that caregiving techniques and active and passive horticultural therapy techniques in Japanese welfare facilities for the elderly are expected to be effective in preventing the progression of cognitive impairment.

Dipeptidyl peptidase-4: A key player in chronic liver disease

Dipeptidyl peptidase-4 (DPP-4) is a membrane-associated peptidase, also known as CD26. DPP-4 has widespread organ distribution throughout the body and exerts pleiotropic effects via its peptidase activity. A representative target peptide is glucagon-like peptide-1, and inactivation of glucagon-like peptide-1 results in the development of glucose intolerance/diabetes mellitus and hepatic steatosis. In addition to its peptidase activity, DPP-4 is known to be associated with immune stimulation, binding to and degradation of extracellular matrix, resistance to anti-cancer agents, and lipid accumulation. The liver expresses DPP-4 to a high degree, and recent accumulating data suggest that DPP-4 is involved in the development of various chronic liver diseases such as hepatitis C virus infection, non-alcoholic fatty liver disease, and hepatocellular carcinoma. Furthermore, DPP-4 occurs in hepatic stem cells and plays a crucial role in hepatic regeneration. In this review, we described the tissue distribution and various biological effects of DPP-4. Then, we discussed the impact of DPP-4 in chronic liver disease and the possible therapeutic effects of a DPP-4 inhibitor.

Intraductal neoplasm of the intrahepatic bile duct: Clinicopathological study of 24 cases

AIM: To investigate the clinicopathological features of intraductal neoplasm of the intrahepatic bile duct (INihB). METHODS: Clinicopathological features of 24 cases of INihB, which were previously diagnosed as biliary papillomatosis or intraductal growth of intrahepatic biliary neoplasm, were reviewed. Mucin immunohistochemistry was performed for mucin (MUC)1, MUC2, MUC5AC and MUC6. Ki-67, P53 and β-catenin immunoreactivity were also examined. We categorized each tumor as adenoma (low grade), borderline (intermediate grade), and malignant (carcinoma in situ , high grade including tumors with microinvasion). RESULTS: Among 24 cases of INihB, we identified 24 tumors. Twenty of 24 tumors (83%) were composed of a papillary structure; the same feature observed in intraductal papillary neoplasm of the bile duct (IPNB). In contrast, the remaining four tumors (17%) showed both tubular and papillary structures. In three of the four tumors (75%), macroscopic mucin secretion was limited but microscopic intracellular mucin was evident. Histologically, 16 tumors (67%) were malignant, three (12%) were borderline, and five (21%) were adenoma. Microinvasion was found in four cases (17%). Immunohistochemical analysis revealed that MUC1 was not expressed in the borderline/adenoma group but was expressed only in malignant lesions (P = 0.0095). Ki-67 labeling index (LI) was significantly higher in the malignant group than in the borderline/adenoma group (22.2 ± 15.5 vs 7.5 ± 6.3, P < 0.01). In the 16 malignant cases, expression of MUC5AC showed borderline significant association with high Ki-67 LI (P = 0.0622). Nuclear expression of β-catenin was observed in two (8%) of the 24 tumors, and these two tumors also showed MUC1 expression. P53 was negative in all tumors. CONCLUSION: Some cases of INihB have a tubular structure, and are subcategorized as IPNB with tubular structure. MUC1 expression in INihB correlates positively with degree of malignancy.

Glycer-AGEs-RAGE signaling enhances the angiogenic potential of hepatocellular carcinoma by upregulating VEGF expression

AIM:To investigate the effect of glyceraldehyde-derived advanced glycation end-products(Glycer-AGEs) on hepatocellular carcinoma(HCC)cells.METHODS:Two HCC cell lines(Hep3B and HepG2 cells)and human umbilical vein endothelial cells(HUVEC)were used.Cell viability was determined using the WST-8 assay.Western blotting,enzyme linked immunosorbent assay,and real-time reverse transcriptionpolymerase chain reactions were used to detect protein and mRNA.Angiogenesis was evaluated by assessing the proliferation,migration,and tube formation of HUVEC.RESULTS:The receptor for AGEs(RAGE)protein was detected in Hep3B and HepG2 cells.HepG2 cells werenot affected by the addition of Glycer-AGEs.GlycerAGEs markedly increased vascular endothelial growth factor(VEGF)mRNA and protein expression,which is one of the most potent angiogenic factors.Compared with the control unglycated bovine serum albumin(BSA) treatment,VEGF mRNA expression levels induced by the Glycer-AGEs treatment were 1.00±0.10 vs 1.92 ±0.09(P<0.01).Similarly,protein expression levels induced by the Glycer-AGEs treatment were 1.63±0.04 ng/mL vs 2.28±0.17 ng/mL for the 24 h treatment and 3.36±0.10 ng/mL vs 4.79±0.31 ng/mL for the 48 h treatment,respectively(P<0.01).Furthermore,compared with the effect of the control unglycated BSA-treated conditioned medium,the Glycer-AGEstreated conditioned medium significantly increased the proliferation,migration,and tube formation of HUVEC,with values of 122.4%±9.0%vs 144.5%±11.3%for cell viability,4.29±1.53 vs 6.78±1.84 for migration indices,and 71.0±7.5 vs 112.4±8.0 for the number of branching points,respectively(P<0.01).CONCLUSION:These results suggest that Glycer-AGEs-RAGE signaling enhances the angiogenic potential of HCC cells by upregulating VEGF expression.

Insulin resistance and chronic liver disease

Increased insulin resistance is frequently associated with chronic liver disease and is a pathophysiological feature of hepatogenous diabetes.Distinctive factors including hepatic parenchymal cell damage,portalsystemic shunting and hepatitis C virus are responsible for the development of hepatogenous insulin resistance/diabetes.Although it remains unclear whether insulin secretion from pancreatic beta cells is impaired as it is in type 2 diabetes,retinopathic and cardiovascular risk is low and major causes of death in cirrhotic patients with diabetes are liver failure,hepatocellular carcinoma and gastrointestinal hemorrhage.Hemoglobin A1c is an inaccurate marker for the assessment and management of hepatogenous diabetes.Moreover,exogenous insulin or sulfonylureas may be harmful because these agents may promote hepatocarcinogenesis.Thus,pathogenesis,cause of death,assessment and therapeutic strategy for hepatogenous insulin resistance/diabetes differ from those for lifestyle-related type 2 diabetes.In this article,we review features of insulin resistance in relationship to chronic liver disease.We also discuss the impact of anti-diabetic agents on interferon treatment and hepatocarcinogenesis.

Prognosis of metastatic splenic hilum lymph node in patients with gastric cancer after total gastrectomy and splenectomy

AIM:To clarify the significance of combined resection of the spleen to dissect the No.10 lymph node(LN). METHODS:We studied 191 patients who had undergone total gastrectomy with splenectomy,excluding non-curative cases,resection of multiple gastric cancer, and those with remnant stomach cancer.Various clinico-pathological factors were evaluated for any independent contributions to No.10 LN metastasis,usingχ 2 test. Significant factors were extracted for further analysis, carried out using a logistic regression method.Furthermore,lymph node metastasis was evaluated for any independent contribution to No.10 LN metastasis,using the same methods.The cumulative survival rate was calculated using the Kaplan-Meier method.The significance of any difference between the survival curves was determined using the Cox-Mantel test,and any difference was considered significant at the 5%level. RESULTS:From the variables considered to be potentially associated with No.10 LN metastasis,age, depth,invasion of lymph vessel,N factor,the numberof lymph node metastasis,Stage,the number of sites, and location were found to differ significantly between those with metastasis(the Positive Group)and those without(the Negative Group).A logistic regression analysis showed that the localization and Stage were significant parameters for No.10 LN metastasis.There was no case located on the lesser curvature in the Posi-tive Group.The numbers of No.2,No.3,No.4sa,No. 4sb,No.4d,No.7,and No.11 LN metastasis were each found to differ significantly between the Positive Group and the Negative Group.A logistic regression analysis showed that No.4sa,No.4sb,and No.11 LN metastasis were each a significant parameter for No.10 LN metastasis.There was no significant difference in survival curves between the Positive Group and the Negative Group. CONCLUSION:Splenectomy should be performed to dissect No.10 LN for cases which have No.4sa,No. 4sb or No.11 LN metastasis.However,in cases where the tumor is located on the lesser curvature,splenectomy can be omitted.

Antibody markers in the diagnosis of inflammatory boweldisease

Inflammatory bowel disease(IBD), including Crohn's disease and ulcerative colitis, is a chronic intestinal inflammation of unknown etiology. The diagnosis of IBD is based on endoscopic, radiologic and histopathologic criteria. Recently, the search for a noninvasive marker that could augment or replace part of this diagnostic process has become a focus of IBD research. In this review, antibody markers, including microbial antibodies, autoantibodies and peptide antibodies, will be described, focusing on their common features. At present, no single marker with qualities that are satisfactory for the diagnosis and treatment of IBD has been identified, although panels of some antibodies are being evaluated with keen interest. The discovery of novel IBD-specific and sensitive markers is anticipated. Such markers could minimize the use of endoscopic and radiologic examinations and could enable clinicians to implement individualized treatment plans designed to improve the long-term prognosis of patients with IBD.

Characteristics and prognosis of synchronous multiple early gastric cancer

AIM:To assess the clinicopathologic characteristics,risk factors,and prognosis for synchronous multiple early gastric cancer(SMGC).METHODS:A total of 146 patients with SMGC and1194 patients with single gastric cancer who had undergone gastrectomy between 1989 and 2008 were retrospectively analyzed to determine their clinicopathologic characteristics and postoperative survival.Tumors were classified into groups on the basis of location and histology.Smoking habits were evaluated using the Brinkman index.Clinical and pathological factors were compared using either Fisher’s exact test or Pearson’sχ2test.Logistic regression analysis was performed to identify independent risk factors.Survival rate was calculated using the Kaplan-Meier method.RESULTS:SMGCs accounted for 10.9%of gastric cancer cases and occurred predominantly in elderly male patients with a family history of gastric cancer who were both smokers and drinkers.These tumors were typically macroscopically elevated and histologically differentiated.There were no significant differences between SMGC and single gastric cancer patients with respect to tumor location,tumor size,lymph node metastasis,the number of metastatic lymph nodes,venous invasion,or tumor stage(P=0.052,P=0.347,P=0.595,P=0.805,P=0.559,and P=0.408,respectively).Further,there was no significant difference in postoperative survival between the patient groups(P=0.200).Of the 146SMGC patients,a single patient had remnant cancer.CONCLUSION:A careful preoperative endoscopy is necessary for patients who are at high risk of SMGC,and minimally invasive treatment may be indicated in some cases.

Immunotherapy in gastric cancer

Gastric cancer is the second most common of cancerrelated deaths worldwide.In the majority of cases gastric cancer is advanced at diagnosis and although medical and surgical treatments have improved,survival rates remain poor.Cancer immunotherapy has emerged as a powerful and promising clinical approach for treatment of cancer and has shown major success in breast cancer,prostate cancer and melanoma.Here,we provide an overview of concepts of modern cancer immunotherapy including the theory,current approaches,remaining hurdles to be overcome,and the future prospect of cancer immunotherapy in the treatment of gastric cancer.Adaptive cell therapies,cancer vaccines,gene therapies,monoclonal antibody therapies have all been used with some initial successes in gastric cancer.However,to date the results in gastric cancer have been disappointing as current approaches often do not stimulate immunity efficiently allowing tumors continue to grow despite the presence of a measurable immune response.Here,we discuss the identification of targets for immunotherapy and the role of biomarkers in prospectively identifying appropriate subjects or immunotherapy.We also discuss the molecular mechanisms by which tumor cells escape host immunosurveillance and produce an immunosuppressive tumor microenvironment.We show how advances have provided tools for overcoming the mechanisms of immunosuppression including the use of monoclonal antibodies to block negative regulators normally expressed on the surface of T cells which limit activation and proliferation of cytotoxic T cells.Immunotherapy has greatly improved and is becoming an important factor in such fields as medical care and welfare for human being.Progress has been rapid ensuring that the future of immunotherapy for gastric cancer is bright.

Status of colitis-associated cancer in ulcerative colitis

Surgical therapy for ulcerative colitis(UC) depends on the medical therapy administered for the patient's condition. UC is a benign disease. However, it has been reported that the rare cases of cancer in UC patients are increasing, and such cases have a worse prognosis. Recently, surgical therapy has greatly changed, there has been quite an increase in the number of UC patients with high-grade dysplasia and/or cancer. These lesions are known as colitis-associated cancer(CAC). The relationship between inflammation and tumorigenesis is well-established, and in the last decade, a great deal of supporting evidence has been obtained from genetic, pharmacological, and epidemiological studies. Inflammatory bowel disease, especially UC, is an important risk factor for the development of colon cancer. We should determine the risk factors for UC patients with cancer based on a large body of data, and we should attempt to prevent the increase in the number of such patients using these newly identified risk factors in the near future. Actively introducing the surgical treatment in addition to medical treatment should be considered. Several physicians should analyze UC from their unique perspectives in order to establish new clinically relevant diagnostic and treatment methods in the future. This article discusses CAC, including its etiology, mechanism, diagnosis, and treatment in UC patients.

Importance of hepatitis C virus-associated insulin resistance:Therapeutic strategies for insulin sensitization

Insulin resistance is one of the pathological features in patients with hepatitis C virus(HCV) infection.Generally,persistence of insulin resistance leads to an increase in the risk of life-threatening complications such as cardiovascular diseases.However,these complications are not major causes of death in patients with HCV-associated insulin resistance.Indeed,insulin resistance plays a crucial role in the development of various complications and events associated with HCV infection.Mounting evidence indicates that HCV-associated insulin resistance may cause(1) hepatic steatosis;(2) resistance to anti-viral treatment;(3) hepatic f ibrosis and esophageal varices;(4) hepatocarcinogenesis and proliferation of hepatocellular carcinoma;and(5) extrahepatic manifestations.Thus,HCV-associated insulin resistance is a therapeutic target at any stage of HCV infection.Although the risk of insulin resistance in HCV-infected patients has been documented,therapeutic guidelines for preventing the distinctive complications of HCV-associated insulin resistance have not yet been established.In addition,mechanisms for the development of HCV-associated insulin resistance differ from lifestyle-associated insulin resistance.In order to ameliorate HCV-associated insulin resistance and its complications,the eff icacy of the following interventions is discussed:a late evening snack,coffee consumption,dietary iron restriction,phlebotomy,and zinc supplements.Little is known regarding the effect of anti-diabetic agents on HCV infection,however,a possible association between use of exogenous insulin or a sulfonylurea agent and the development of HCC has recently been reported.On the other hand,insulin-sensitizing agents are reported to improve sustained virologic response rates.In this review,we summarize distinctive complications of,and therapeutic strategies for,HCVassociated insulin resistance.Furthermore,we discuss supplementation with branched-chain amino acids as a unique insulin-sensitizing strategy for patients with HCVassociated insulin resistance.

Clinical characteristics and management of gastric tube cancer with endoscopic submucosal dissection

AIM:To identify the characteristics of gastric tube cancer(GTC) and the complications associated with endoscopic submucosal dissection(ESD) for GTC.METHODS:Between 2007 and 2012,11 individualswith early gastric cancer in the reconstructed gastric tube after esophagectomy who underwent ESD in this hospital were studied.The characteristics of GTC were identified,and the complications of ESD for GTC were analyzed at three phases:preoperative,intraoperative,and postoperative.RESULTS:A total of 11 consecutive patients with 11 GTCs were selected for this study.All cases underwent en bloc resections by ESD.The median procedure time was 142 min.The average GTC diameter was 26.1 mm,and the average size of the resected lesions was 45.5 mm.The histopathological diagnosis in all cases was a differentiated adenocarcinoma.In the preoperative phase,anastomotic strictures(5/11,45%) and food residues(4/11,36.4%) in the gastric tube were the main complications.In the intraoperative phase,bleeding was observed in 5 cases(45%).The postoperative complications observed were delayed bleeding in 2 cases(18.2%) and stenosis in one case(9.1%).The case with stenosis was successfully treated using endoscopic balloon dilatation.CONCLUSION:Minor complications were frequently observed.However,all GTCs underwent en bloc resection with ESD without any serious complications.ESD is considered a useful treatment for GTC.

Chemotherapy and molecular targeting therapy for recurrent cervical cancer

For patients with primary stage IVB, persistent, or recurrent cervical cancer, chemotherapy remains the standard treatment, although it is neither curative nor associated with long-term disease control. In this review, we summarized the history of treatment of recurrent cervical cancer, and the current recommendation for chemotherapy and molecular targeted therapy. Eligible articles were identified by a search of the MEDLINE bibliographical database for the period up to November 30, 2014. The search strategy included the following any or all of the keywords： ＂uterine cervical cancer＂, ＂chemotherapy＂, and ＂targeted therapies＂. Since cisplatin every 21 days was considered as the historical standard treatment for recurrent cervical cancer, subsequent trials have evaluated and demonstrated activity for other agents including paclitaxel, gemcitabine, topotecan and vinorelbine among others. Accordingly, promising agents were incorporated into phase III trials. To examine the best agent to combine with cisplatin, several landmark phase III clinical trials were conducted by Gynecologic Oncology Group （GOG） and Japan Clinical Oncology Group （JCOG）. Through, GOG204 and JCOG0505, paclitaxel/cisplatin （TP） and paclitaxel/carboplatin （TC） are now considered to be the recommended therapies for recurrent cervical cancer patients. However, the prognosis of patients who are already resistant to chemotherapy, are very poor. Therefore new therapeutic strategies are urgently required. Molecular targeted therapy will be the most hopeful candidate of these strategies. From the results of GOG240, bevacizumab combined with TP reached its primary endpoint of improving overall survival （OS）. Although, the prognosis for recurrent cervical cancer patients is still poor, the results of GOG240 shed light on the usefulness of molecular target agents to chemotherapy in cancer patients. Recurrent cervical cancer is generally considered incurable and current chemotherapy regiments offer only modest gains in OS, particularly for patients with multiple poor prognostic factors. Therefore, it is crucial to consider not only the survival benefit, but also the minimization of treatment toxicity, and maximization of quality of life （QOL）.

Diagnosis of early gastric cancer using narrow band imaging and acetic acid

AIM: To determine whether the endoscopic findings of depressed-type early gastric cancers(EGCs) could precisely predict the histological type.METHODS: Ninety depressed-type EGCs in 72 patients were macroscopically and histologically identified. We evaluated the microvascular(MV) and mucosal surface(MS) patterns of depressed-type EGCs using magnifying endoscopy(ME) with narrow-band imaging(NBI)(NBI-ME) and ME enhanced by 1.5% acetic acid, respectively. First, depressed-type EGCs were classified according to MV pattern by NBI-ME. Subsequently, EGCs unclassified by MV pattern were classified according to MS pattern by enhanced ME(EME) images obtained from the same angle.RESULTS: We classified the depressed-type EGCs into the following 2 MV patterns using NBI-ME: a fine-network pattern that indicated differentiated adenocarcinoma(25/25, 100%) and a corkscrew pattern that likely indicated undifferentiated adenocarcinoma(18/23, 78.3%). However, 42 of the 90(46.7%) lesions could not be classified into MV patterns by NBI-ME. These unclassified lesions were then evaluated for MS patterns using EME, which classified 33(81.0%) lesions as MS patterns, diagnosed as differentiated adenocarcinoma. As a result, 76 of the 90(84.4%) lesions were matched with histological diagnoses using a combination of NBI-ME and EME.CONCLUSION: A combination of NBI-ME and EME was useful in predicting the histological type of depressedtype EGC.

study to determine guidelines for pediatric colonoscopy

AIM To investigated characteristics, diagnosis, bowelcleansing preparation, sedation, and colonoscope length and diameter in Japanese pediatric patients receiving total colonoscopy.METHODS The present study evaluated consecutive patients aged ≤ 15 years who had undergone their first colonoscopy in Kurume University between January 2007 and February 2015. Data were retrospectively analyzed. We identified 110 pediatric patients who had undergone colonoscopy that had reached the cecum, allowing the observation of the total colon.RESULTS Hematochezia, abdominal pain, and diarrhea were the most common symptoms. For bowel-cleansing preparation, pediatric patients aged ≤ 12 years were treated with magnesium citrate, and patients aged 13-15 years were treated with polyethylene glycol 4000. For sedation, thiamylal with pentazocine, which has an analgesic effect, was used in patients aged ≤ 6 years, and midazolam with pentazocine was used in patients aged ≥ 7 years. Regarding the choice of endoscope, short and thin endoscopes were selected for younger patients, particularly patients aged ≤ 3 years. Positive diagnoses were made in 78 patients(70.9%). Inflammatory bowel disease(n = 49, 44.5%), including ulcerative colitis(n = 37, 33.6%) and Crohn's disease(n = 12, 10.9%), was the most common diagnosis. CONCLUSION Colonoscopy offers a high diagnostic capability for pediatric patients with gastrointestinal symptoms. The selection of appropriate management the performance of colonoscopy is important in pediatric patients.

Liver cell adenoma with malignant transformation:A case report

A 57-year-old woman was referred to our hospital because of a liver mass detected by computed tomography. She had taken oral contraceptives for only one month at the age of thirty. Physical examination revealed no abnormalities, and laboratory data, including hepatic function tests, were within the normal range, with the exception of elevated levels of those serum proteins induced by the absence of vitamin K or by raised levels of the antagonist (PIVKA)-Ⅱ (3 502 AU/ml).Abdominal ultrasonography revealed a hyperechoic mass measuring 10x10 cm in the left posterior segment of the liver. Because hepatocellular carcinoma could not be completely excluded, this mass was resected. The tumor consisted of sheets of uniform cells with clear cytoplasm,perinuclear eosinophilic granules and round nuclei. These histological findings were consistent with liver cell adenoma.Background hepatic tissue appeared normal. After resection of the tumor, serum PIVKA-Ⅱ fell to within the normal range.An area of hepatocellular carcinoma (HCC) with a midtrabecular pattern was immunohistochemically found, which was positive for PIVKA-Ⅱ. Sinusoidal endothelial cells were CD34-positive, containing scattered PIVKA-Ⅱ positive cells.This tumor was therefore finally diagnosed as liver cell adenoma with focal malignant transformation to HCC.

Prediction of colorectal tumor grade and invasion depth through narrow-band imaging scoring

AIM To determine the usefulness of assigning narrow-band imaging(NBI) scores for predicting tumor grade and invasion depth in colorectal tumors.METHODS A total of 161 colorectal lesions were analyzed from138 patients who underwent endoscopic or surgical resection after conventional colonoscopy and magnifying endoscopy with NBI. The relationships between the surface and vascular patterns of the lesions, as visualized with NBI, and the tumor grade and depth of submucosa(SM) invasion were determined histopathologically.Scores were assigned to distinct features of the surface microstructures of tubular and papillary-type lesions.Using a multivariate analysis, a model was developed for predicting the tumor grade and depth of invasion based on NBI-finding scores.RESULTS NBI findings that correlated with a high tumor grade were associated with the "regular/irregular"(P < 0.0001)surface patterns and the "avascular area" pattern(P =0.0600). The vascular patterns of "disrupted vessels"(P = 0.0714) and "thick vessels"(P = 0.0133) but none of the surface patterns were associated with a depth of invasion of ≥ 1000 μm. In our model, a total NBIfinding score ≥ 1 was indicative of a high tumor grade(sensitivity: 0.97; specificity: 0.24), and a total NBIfinding score ≥ 9(sensitivity: 0.56; specificity: 1.0) was predictive of a SM invasion depth ≥ 1000 μm. Scores less than these cutoff values signified adenomas and a SM invasion depth < 1000 μm, respectively. Associations were also noted between selected NBI findings and tumor tissue architecture and histopathology.CONCLUSION Our multivariate statistical model for predicting tumor grades and invasion depths from NBI-finding scores may help standardize the diagnosis of colorectal lesions and inform therapeutic strategies.

Molecular targeting to treat gastric cancer

Trastuzumab that targets human epidermal growth factor receptor 2(HER2) protein is the only approved molecular targeting agent for treating gastric cancer in Japan and the outcomes have been favorable. However,trastuzumab is effective for only 10% to 20% of the population with gastric cancer that expresses HER2 protein. Molecular targeting therapy with bevacizumab against vascular endothelial growth factors(VEGF) and with cetuximab and panitumumab against the epidermal growth factors pathway that have been approved for treating colorectal cancer are not considered effective for treating gastric cancer according to several clinical trials. However,ramucirumab that targets VEGF receptor-2 prolonged overall survival in a large phase Ⅲ clinical trial and it might be an effective molecular targeting therapy for gastric cancer. The significance of molecular targeting therapy for gastric cancer remains controversial. A large-scale randomized clinical trial of novel molecular targeting agents with which to treat gastric cancer is needed.