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KML001, an arsenic compound, as salvage chemotherapy in refractory biliary tract cancers: A prospective study

Hepatobiliary & Pancreatic Diseases International 2019年第1期18卷 62-66页

作者： Jung Hyun Jo Huapyong Kang Hee Seung Lee Moon Jae Chung Jeong Youp Park Seungmin Bang Seung Woo Park Si Young Song Division of gastroenterology Department of Internal Medicine Severance Hospital Yonsei University College of Medicine

Background: Sodium meta-arsenite(NaAsO_2, KML001) is a potential oral anticancer agent acting on telomerase and telomere length. This prospective study evaluated its safety, tolerability, and effectiveness as salvage chemotherapy in patients with advanced biliary tract cancer(BTC) resistant to gemcitabinebased chemotherapy. Methods: Forty-four patients(21 women and 23 men) with advanced BTC and failure history of gemcitabine-based chemotherapy, performance status(PS) 0–2, normal cardiac, hepatic, and renal function were enrolled. Daily dose of KML001(7.5 mg. p.o.) was administered to eligible subjects for 24 weeks divided into six treatment cycles. Response was evaluated bimonthly using CT. Results: After an average of 1.5 months of treatment(range: 0.5–10.0), 3 patients(6.8%) obtained progression-free status, 23 patients(52.3%) had disease progression, and 18 patients(40.9%) dropped out before evaluation. One patient(2.3%) completed six treatment cycles without progression. During the treatment, morphine dosage kept the same or decreased in 20 patients(47.6%). Nine patients(20.5%) experienced grade-3 adverse events(AEs), while no patient experienced grade-4 AEs. The most common AEs were liver enzyme elevation(11/44, 25%) and anemia(10/44, 22.7%). KML001 was discontinued in six patients(13.6%) due to AEs, including liver toxicity( n = 3), QTc prolongation( n = 2), and abdominal pain( n = 1). Conclusions: KML001 did not have enough anticancer effect on patients with advanced BTC resistant to gemcitabine. However, KML001 was safe and well-tolerable in terms of AEs and pain control when used as salvage therapy. Further studies are needed to establish arsenic agents as a reliable treatment option in patients with BTC.

关键词： Biliary tract neoplasms Cholangiocarcinoma Gallbladder neoplasms KML001 Sodium meta-arsenite

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Risk factors and metabolic abnormality of patients with non-alcoholic fatty liver disease: Either non-obese or obese Chinese population

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Hepatobiliary & Pancreatic Diseases International 2018年第1期17卷 45-48页

作者： Shou-Wu Lee Teng-Yu Lee Sheng-Shun Yang Chun-Fang Tung Hong-Zen Yeh Chi-Sen Chang Division of gastroenterology Department of Internal Medicine Taichung Veterans General Hospital

Background: Non-alcoholic fatty liver disease(NAFLD) occurs not only in obese individuals but also in non-obese ones. The aim of this study was to focus on the association between NAFLD and metabolic events in a non-obese or obese Chinese ***: Data collected from subjects registered at Taichung Veterans General Hospital from January to December 2009 were analyzed. The exclusion criteria were alcoholics, chronic hepatitis B or C. Patients included in analyses were assigned to four groups according to sonography of their liver(normal or NAFLD), and body mass index(BMI) levels(non-obese if BMI iver(group A), non-obese NAFLD(group B), obese normal liver(group C) and obese NAFLD(group D),respectively. The highest ratio of metabolic syndrome existed in the group B(26.9%), followed by group A(11.7%), group D(10.9%) and finally the group C(5.2%). The positive association with NAFLD in non-obese individuals was significant in triglyceride(OR = 1.01; 95% CI: 1.01–1.02) and glucose(OR = 1.02; 95% CI:1.01–1.03), while the positive association with NAFLD in obese subjects was only significant in triglyceride(OR = 1.01; 95% CI: 1.01–1.02). The positive association was most significant in all cases(adjusted OR = 2.41; 95% CI: 1.78–3.24), especially in non-obese individuals(OR = 2.81; 95% CI: 1.92–4.12).Conclusions: Non-obese NAFLD subjects displayed a higher proportion of metabolic abnormality. Hyperlipidemia and hyperglycemia had the most positive strength association with NAFLD.

关键词： Fatty liver Non-alcoholic fatty liver disease Obese Chinese population

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Long-term pretreatment with proton pump inhibitor and Helicobacter pylori eradication rates

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World Journal of gastroenterology 2014年第4期20卷 1061-1066页

作者： Seung Bae Yoon Jae Myung Park Jong-Yul Lee Myong Ki Baeg Chul-Hyun Lim Jin Soo Kim Yu Kyung Cho In Seok Lee Sang Woo Kim Myung-Gyu Choi Division of gastroenterology Department of Internal Medicine College of Medicine The Catholic University of Korea

AIM: To investigate whether proton pump inhibitor (PPI) pretreatment influences Helicobacter pylori eradication rate.

关键词： Proton pump inhibitor Helicobacter pylori Urea breath test Antibiotics Drug resistance

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Effect of tumor necrosis factor-α antagonists on oxidative stress in patients with Crohn's disease

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World Journal of gastroenterology 2015年第35期21卷 10208-10214页

作者： Kazunari Yamamoto Toshimi Chiba Takayuki Matsumoto Division of gastroenterology Department of Internal MedicineSchool of MedicineIwate Medical University

AIM: To investigate changes in oxidative stress in Crohn's disease(CD) before and after anti-tumor necrosis factor(TNF)-α ***: A total of 42 patients with active CD, who were scheduled to be treated by anti-TNF-α antibodies, were enrolled. Serum levels of diacron-reactive oxygen metabolites(d-ROM), biological antioxidant potential(BAP), and modified ratio of oxidative stress and antioxidant capacity(m-OA) were measured using the Free Radical Analytical System before and 8 wk after induction of therapy with infliximab or adalimumab. The values for oxidative stress were correlated with disease activity and clinical response as determined by the CD activity index(CDAI) at 8 and 54 wk after the ***: Prior to treatment, d-ROM showed significant correlations with CDAI(r = 0.42, P ive correlation between m-OA and CDAI before and after treatment(r =-0.48 vs r =-0.42, P ive stress in patients with CD, but does not alter the production of antioxidants. Dysregulation of antioxidants may be associated with the disease.

关键词： Crohn’s disease Severity Oxidative stress Anti-tum

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Comparison of scoring systems in predicting the severity of acute pancreatitis

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World Journal of gastroenterology 2015年第8期21卷 2387-2394页

作者： Joon Hyun Cho Tae Nyeun Kim Hyun Hee Chung Kook Hyun Kim Division of gastroenterology and Hepatology Department of Internal Medicine Yeungnam University College of Medicine

AIM:To investigate the prognostic usefulness of several existing scoring systems in predicting the severity of acute pancreatitis(AP).METHODS:We retrospectively analyzed the prospectively collected clinical database from consecutive patients with AP in our institution between January 2011 and December ***,Acute Physiology and Chronic Health Evaluation(APACHE)-Ⅱ,and bedside index for severity in acute pancreatitis(BISAP)scores,and computed tomography severity index(CTSI)of all patients were *** C-reactive protein(CRP)levels were measured at admission(CRPi)and after 24h(CRP24).Severe AP was defined as persistent organ failure for more than 48 *** predictive accuracy of each scoring system was measured by the area under the receiver-operating curve(AUC).RESULTS:Of 161 patients,21(13%)were classified as severe AP,and 3(1.9%)*** significant cutoff values for prediction of severe AP were Ranson≥3,BISAP≥2,APACHE-Ⅱ≥8,CTSI≥3,and CRP24≥*** for Ranson,BISAP,APACHE-Ⅱ,CTSI,and CRP24 in predicting severe AP were 0.69(95%CI:0.62-0.76),0.74(95%CI:0.66-0.80),0.78(95%CI:0.70-0.84),0.69(95%CI:0.61-0.76),and0.68(95%CI:0.57-0.78),***-Ⅱdemonstrated the highest accuracy for prediction of severe AP,however,no statistically significant pairwise differences were observed between APACHE-Ⅱand the other scoring systems,including ***:Various scoring systems showed similar predictive accuracy for severity of *** models are needed in order to achieve further improvement of prognostic accuracy.

关键词： Severity Scoring systems Predictors Acute pancreat

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Biermer’s Disease at the Donka National Hospital in Guinea—Epidemio-Clinical, Therapeutic and Evolutionary Aspect in the internal medicine department

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Open Journal of internal medicine 2023年第3期13卷 218-224页

作者： Thierno Amadou Wann Mamadou Sarifou Diallo Djenabou Diallo Kadiatou Diallo Mamadou Lamine Yaya Bah Mamadou Diakhaby Mohamed Cissoko Amadou Kaké Djibril Sylla department of internal medicine Teaching Hospital of Conakry Conakry Guinea department of Hepato-gastroenterology University Hospital of Conakry Conakry Guinea

Introduction: Biermer’s disease is an autoimmune disease characterized by a lack of absorption of vitamin B12 in connection with the production of antibodies (A) destroying the intrinsic factor (IF) which allows the absorption of vitamin B12 (cobalamin). These clinical manifestations are polymorphic and severe in our context. The objective of this work is to identify the epidemiological-clinical, therapeutic and evolutionary characteristics of Biermer’s disease in Guinean population. Materials and methods: This was a retrospective of patient files followed for Biermer’s disease at the internal medicine department of Donka National Hospital from January 2012 to December 2021. Results: Eight patients were included including 5 women and 3 men. The average age of the patients was 48 years old. The diagnostic delay was 3.6 years on average. All our patients had bioclinical anemia (8 cases, i.e. 100%) followed by epigastralgia in 4 cases (50%), neurological damage such as sensitive polyneuropathy in 3 cases (37.5%). Four patients had acquired melanoderma (50%). Hypovitaminosis B12 was found in 4 patients. The myelogram performed in three patients (37.5%) found medullary megaloblastosis. One patient had Hashimoto’s disease associated with Biermer’s disease in endoscopy, (FOGD) found fundica trophy on macroscopy in 4 cases (50%). Treatment consisted of B12 vitamin therapy in all cases with a favorable clinical and biological outcome. Conclusion: Biermer’s disease remains common in Africa and is characterized at a younger age in addition to the severity of clinical and biological manifestations. The care consists of taking vitamin B12 which remains accessible in our context.

关键词： Biermer’s Disease Donka Aspects Epidemiological-Clinical Therapeutics

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Role of new endoscopic techniques in inflammatory bowel disease management: Has the change come?

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World Journal of gastroenterology 2017年第24期23卷 4324-4329页

作者： loredana goran lucian negreanu ana maria negreanu internal medicine Ⅱ gastroenterology department University Hospital Carol Davila University of Medicine

Despite significant therapeutic progress in recent years,inflammatory bowel disease(IBD),which includes Crohn’s disease and ulcerative colitis,remains a challenge regarding its pathogenesis and long-term *** concepts have emerged in the management of this disease,such as the"treat-totarget"concept,in which mucosal healing plays a key role in the evolution of IBD,the risk of recurrence and the need for *** is essential for the assessment of mucosal inflammation and plays a pivotal role in the analysis of mucosal healing in patients with *** is also essential in the detection of dysplasia and in the identification of the risk of colon *** current surveillance strategy for dysplasia in IBD patients indicates white-light endoscopy with non-targeted *** new chromoendoscopy techniques provide substantial benefits for both clinicians and ***-band imaging(NBI)has similar rates of dysplastic lesion detection as whitelight endoscopy,and it seems that NBI identifies more adenoma-like *** it is used instinctively by many endoscopists,the combination of these two techniques might improve the rate of dysplasia *** spectral imaging color enhancement can help differentiate dysplastic and non-dysplastic lesions and can also predict the risk of recurrence,which allows us to modulate the treatment to gain better control of the *** combination of noninvasive serum and stool biomarkers with endoscopy will improve the monitoring and limit the evolution of IBD because it enables the use of a personalized approach to each patient based on that patient’s history and risk factors.

关键词： Chromoendoscopy Flexible spectral imaging color enhancement Inflammatory bowel disease Dysplasia Mucosal healing Narrow band imaging

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Recent advances in treatment of nodal and gastrointestinal follicular lymphoma

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World Journal of gastroenterology 2023年第23期29卷 3574-3594页

作者： Takuya Watanabe department of internal medicine and gastroenterology Watanabe Internal Medicine Aoyama ClinicNiigata-city 9502002Japan

Follicular lymphoma(FL)is the most common low-grade lymphoma,and although nodal FL is highly responsive to treatment,the majority of patients relapse repeatedly,and the disease has been incurable with a poor ***,primary FL of the gastrointestinal tract has been increasingly detected in Japan,especially due to recent advances in small bowel endoscopy and increased opportunities for endoscopic examinations and endoscopic ***,many cases are detected at an early stage,and the prognosis is good in many *** contrast,in Europe and the United States,gastrointestinal FL has long been considered to be present in 12%-24%of Stage-iv patients,and the number of advanced gastrointestinal cases is expected to *** editorial provides an overview of the recent therapeutic advances in nodal FL,including antibody-targeted therapy,bispecific antibody therapy,epigenetic modulation,and chimeric antigen receptor T-cell therapy,and reviews the latest therapeutic manuscripts published in the past *** on an understanding of the therapeutic advances in nodal FL,we also discuss future possibilities for gastroenterologists to treat gastrointestinal FL,especially in advanced cases.

关键词： Nodal and gastrointestinal follicular lymphoma Antibody-based therapy Bispecific antibody therapy Phosphatidylinositol-3 kinase inhibitor Epigenetic modulator Chimeric antigen receptor-T cell therapy

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Efficacy of 0.5-L vs 1-L polyethylene glycol containing ascorbic acid as additional colon cleansing methods for inadequate bowel preparation as expected by last stool examination before colonoscopy

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World Journal of Clinical Cases 2019年第1期7卷 39-48页

作者： Joon Hyun Cho Eun Joo Goo Kyeong Ok Kim Si Hyung Lee Byung Ik Jang Tae Nyeun Kim Division of gastroenterology and Hepatology Department of Internal Medicine Yeungnam University College of Medicine

BACKGROUND No consensus has been reached in patients suspected of having inadequate bowel preparation regarding optimal salvage methods, which negatively affects the efficacy and quality of colonoscopy. The most ideal and reasonable rescue option involves early suspicion and identification of patients with inadequate preparation before sedation, additional oral ingestion of a suitable preparation formulation, and same-day *** To compare 0.5-L and 1-L polyethylene glycol containing ascorbic acid(PEG +Asc) as additional bowel cleansing methods after a 2-L split-dose PEG + Asc regimen in patients with expected inadequate bowel preparation before *** Individuals with expected inadequate bowel preparation based on last stool form, such as turbid liquid, particulate liquid, or liquid with small amounts of feces, were randomized to either a 0.5-L PEG + Asc group or a 1-L PEG + Asc group. The primary endpoint was bowel preparation as assessed using the Aronchick bowel preparation scale(ABPS) and Boston bowel preparation scale(BBPS) scores. The secondary endpoints were cecal intubation time, withdrawal time, polyp detection rate(PDR), adenoma detection rate(ADR), individual compliance with additional PEG + Asc, and patient *** Initially, 98 patients were included, but 8 were later excluded due to withdrawal of consent to participate in the study. Adequate bowel preparation(as assessed by ABPS) was observed in 80.9%(38/47) of subjects in the 0.5-L group and in88.4%(38/43) of subjects in the 1-L group(P = 0.617). Mean total BBPS was 6.7 points in the 0.5-L group and 7.0 points in the 1-L group(P = 0.458). ADRs and PDRs were similar in the two groups, and cecal intubation and withdrawal times were not significantly different. However, mean patient satisfaction score was significantly higher in the 0.5-L group(P = 0.041).CONCLUSION The bowel cleaning efficacy of additional 0.5-L PEG + Asc was not inferior to that of 1-L PEG + Asc. Add

关键词： Inadequate bowel preparation Additional colon cleansing Colonoscopy Polyethylene glycol

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Mouse models for investigating the underlying mechanisms of nonalcoholic steatohepatitis-derived hepatocellular carcinoma

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World Journal of gastroenterology 2018年第18期24卷 1989-1994页

作者： Kazuki Takakura Tsunekazu Oikawa Yoichi Tomita Yusuke Mizuno Masanori Nakano Chisato Saeki Yuichi Torisu Masayuki Saruta Division of gastroenterology and Hepatology Department of Internal Medicine The Jikei University School of Medicine

As the incidence of hepatocellular carcinoma(HCC) caused by infection with the hepatotropic viruses hepatitis B and hepatitis C decreases, greater attention has become focused on HCC caused by nonalcoholic steatohepatitis(NASH), an advanced form of nonalcoholic fatty liver disease which has shown increasing prevalence in correspondence with the overall increase in metabolic syndrome over the recent decades. Several clinical population studies have shown a positive relationship between NASH and HCC, while also providing initial insights into the underlying mechanisms of HCC development from NASH. Research into the pathological progression of NASH to HCC has advanced by use of several beneficial rodent models. In this review, we summarize the established mouse models for preclinical research of NASH-associated HCC and discuss the underlying hepatic mechanisms of NASH-related tumorigenesis identified to date that could lead to new targets for treatment and prevention.

关键词： Hepatocellular carcinoma Nonalcoholic steatohepatitis Nonalcoholic fatty liver disease

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