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Gene targeted and immune therapies for nodal and gastrointestinal follicular lymphomas

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World Journal of Gastroenterology 2023年第48期29卷 6179-6197页

作者： Takuya watanabe Department of Internal Medicine and Gastroenterology Watanabe Internal Medicine Aoyama ClinicNiigata 9502002Japan

Follicular lymphoma(FL)is the most common indolent B-cell lymphoma(BCL)***,its incidence has increased in Europe,the United States,and Asia,with the number of gastrointestinal FL cases expected to *** abnormalities related to t(14;18)translocation,BCL2 overexpression,NF-κB pathway-related factors,histone acetylases,and histone methyltransferases cause FL and enhance its ***,microRNAs are commonly used in diagnosing FL and predicting patient *** clinical trials on novel therapeutics targeting these genetic abnormalities and immunomodulatory mechanisms have been conducted,resulting in a marked improvement in therapeutic outcomes for *** developing these innovative therapeutic agents targeting specific genetic mutations and immune pathways has provided hope for curative options,FL treatment has become more complex,requiring combinatorial therapeutic ***,optimal treatment combinations have not yet been achieved,highlighting the importance of a complete understanding regarding the pathogenesis of gastrointestinal ***,this article reviews key research on the molecular pathogenesis of nodal FL and novel therapies targeting the causative genetic ***,the results of clinical trials are summarized,with a particular focus on treating nodal and gastrointestinal FLs.

关键词： Gastrointestinal follicular lymphoma Genetic mutation analysis using nextgeneration sequencing MicroRNA Gene targeted therapy Immune therapy

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

Ultrasound-guided rectus sheath block for anterior cutaneous nerve entrapment syndrome after laparoscopic surgery:A case report

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World Journal of clinical Cases 2022年第7期10卷 2357-2362页

作者： Ryuji Sawada Kunitaro watanabe Joho Tokumine Alan Kawarai Lefor Tadao Ando Tomoko Yorozu Department of Pain clinic NTT Medical Center TokyoHigashigotanda 141-8625TokyoJapan Department of Anesthesiology Hino Municipal HospitalTamadaira 191-0062TokyoJapan Department of Anesthesiology Kyorin University School of MedicineMitaka 181-8611TokyoJapan Department of Surgery Jichi Medical UniversityShimotsuke 329-0498TochigiJapan

BACKGROUND Anterior cutaneous nerve entrapment syndrome is defined as abdominal pain due to entrapped intercostal *** is the first report of a patient successfully treated for anterior cutaneous nerve entrapment syndrome after laparoscopic surgery with an ultrasound-guided rectus sheath *** rectus sheath block physically lysed adhesions and relieved pain from anterior cutaneous nerve entrapment *** SUMMARY The patient is a 44-year-old man who presented with severe left upper abdominal pain at an operative scar one month after laparoscopic ulcer *** and treatment were performed using an ultrasound-guided rectus sheath block with 0.1%lidocaine 20 *** pain was relieved after the *** diagnosis was anterior cutaneous nerve entrapment *** sheath block may be effective for patients with anterior cutaneous nerve entrapment *** Ultrasound-guided rectus sheath block is a promising treatment modality for patients with postoperative anterior cutaneous nerve entrapment syndrome due to adhesions.

关键词： Anterior cutaneous nerve entrapment syndrome Rectus sheath block Hydrodissection Laparoscopic surgery Case report

Effects of long-term monotherapy with glimepiride vs glibenclamide on glycemic control and macrovascular events in Japanese Type 2 diabetic patients

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Journal of Diabetes Mellitus 2014年第1期4卷 33-37页

作者： Hirohisa Onuma Kouichi Inukai Masaki watanabe Yoshikazu Sumitani Toshio Hosaka Hitoshi Ishida Third Department of Internal Medicine Kyorin University School of Medicine Tokyo Japan watanabe medical clinic Hiroshima Japan

We investigated whether long-term glimepiride (GP) monotherapy improves insulin resistance and exerts a beneficial effect on beta cell function, as compared with glibenclamide (GC). One hundred Japanese Type 2 diabetic patients were randomly assigned to the GP (n = 50) or the GC (n = 50) group. During a 5-year monitoring period, patients received the indicated SU monotherapy, while changes in SU doses were allowed as needed to maintain HbA1C below 7.0%. The GC group, in parallel with fasting insulin, showed a rapid homeostatic model assessment (HOMA)-R increase and maintained a high HOMA-R level. In contrast, HOMA-R in the GP group decreased continuously, from 2.9 at baseline to 1.8 at study completion. In the GC group, HOMA-b was markedly increased in the first 6 months, then gradually decreased through 18 months. While the HOMA-β elevation in the GP group was more moderate than that in the GC group, HOMA-β levels were maintained with a slight decrease. The cumulative macrovascular disease outcome was 1 for the GP and 7 for the GC group, showing a significant difference. These results suggest that glimepiride monotherapy markedly improved HOMA-R with moderate insulin stimulation, which may account for the difference in macrovascular disease development as compared with the group receiving glibenclamide.

关键词： Glibenclamide Glimepiride Macrovascular Events HOMA-R/β

Helicobacter pylori infection in subjects negative for high titer serum antibody

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World Journal of Gastroenterology 2018年第13期24卷 1419-1428页

作者： Osamu Toyoshima Toshihiro Nishizawa Masahide Arita Yosuke Kataoka Kosuke Sakitani Shuntaro Yoshida Hiroharu Yamashita Keisuke Hata Hidenobu watanabe Hidekazu Suzuki Department of Gastroenterology Toyoshima Endoscopy Clinic Department of Pathology Pathology and Cytology Laboratory Japan medical Education Center Keio University School of Medicine

AIM To investigate the clinicopathological features of the patients testing negative for high titer serum antiHelicobacter pylori(H. pylori) *** The antibody titers were measured using antigens derived from Japanese individuals. ^(13)C-urea breath test-positive individuals were defined as having H. pylori infection. We investigated the demographic characteristics, laboratory data, endoscopic findings including Kyoto classification of gastritis, and histology in negative-high titer patients without H. pylori eradication therapy. Kyoto classification consisted of scores for gastric atrophy, intestinal metaplasia, enlarged folds, nodularity, and *** Of the 136 subjects enrolled, 23(17%) had H. pylori infection. Kyoto classification had an excellent area under the receiver operating characteristics curve(0.886, 95% confidence interval: 0.803-0.968, P = 3.7 × 10^(-20)) for predicting H. pylori infection with a cutoff value of 2. Further, Kyoto classification, H. pylori density, and neutrophil activity had high accuracies(89.7%, 96.3%, and 94.1%, respectively). Kyoto classification was independent of the demographic and laboratory parameters in multivariate *** Endoscopic Kyoto classification of gastritis is a useful predictor of H. pylori infection in negative-high titer antibody patients.

关键词： Kyoto classification Gastritis Helicobacter pylori Antibody Endoscopy

Efficacy and safety of telaprevir- and simeprevir-based triple therapies for older patients with chronic hepatitis C

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World Journal of Hepatology 2017年第5期9卷 252-262页

作者： Satoshi Yamagiwa Toru Ishikawa Nobuo Waguri Soichi Sugitani Hiroto Wakabayashi Shogo Ohkoshi Takashi Tsukishiro Toru Takahashi Toshiaki watanabe Shuji Terai Division of Gastroenterology and Hepatology Niigata University Graduate School of Medical and Dental Sciences Department of Gastroenterology and Hepatology Saiseikai Niigata Daini Hospital Department of Gastroenterology and Hepatology Niigata City General Hospital Department of Gastroenterology and Hepatology Tachikawa General Hospital Department of Gastroenterology and Hepatology Takeda General Hospital Department of Internal Medicine Nippon Dental University Medical Hospital Department of Internal Medicine Itoigawa General Hospital Department of Internal Medicine Uonuma Hospital watanabe clinic

AIM To evaluate and compare the efficacy and safety of telaprevir(TVR)-and simeprevir(SMV)-based triple therapies in elderly patients, specifically patients aged 66 years or *** The present study enrolled 112 and 76 Japanese patients with chronic hepatitis C virus genotype 1b infection who were treated with a 12-wk TVR-based or SMV-based triple therapy, respectively, followed by a dual therapy that included pegylated interferon α and ribavirin(RBV) for 12 wk. The patients were categorized into two groups according to age as follows: A younger group of patients aged ≤ 65 years old and an older group of patients aged > 65 years old. Among the patients treated with TVR-based triple therapy, 34 patients were included in the older group. The median ages were 56 years(range: 28-65 years) in the younger group and 69 years(range: 66-81 years) in the older group. Among the patients treated with SMV-based triple therapy, 39 patients were included in the older group. The median ages were 59 years(range: 36-65 years) in the younger group and 71 years(range: 66-86 years) in the older group. The clinical, biochemical and virological data were analyzed before and during *** Among the patients treated with the TVR-based triple therapy, no significant difference in the sustained virological response(SVR) was found between the younger(80.8%) and older(88.2%) groups. The SVR rates for patients with the interleukin 28B(IL28B)(rs8099917) TG/GGgenotypes(73.9% and 60.0% in the younger and older groups, respectively) were significantly lower than for patients with the IL28B TT-genotype(86.3% and 92.9%, respectively). The cumulative exposure to RBV for the entire 24-wk treatment period(as a percentage of the target dose) was significantly higher in the younger group than in the older group(91.7% vs 66.7%, respectively, P < 0.01), but the cumulative exposure to TVR was not significantly different between the younger and older groups(91.6% vs 81.9%, respectively). A mu

关键词： Telaprevir 年老的病人丙肝病毒遗传型 1b Interleukin 28B Simeprevir

Brown slits for colorectal adenoma crypts on conventional magnifying endoscopy with narrow band imaging using the X1 system

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World Journal of Gastroenterology 2022年第24期28卷 2748-2757页

作者： Osamu Toyoshima Toshihiro Nishizawa Shuntaro Yoshida Hidenobu watanabe Nariaki Odawara Kosuke Sakitani Toru Arano Hirotoshi Takiyama Hideyuki Kobayashi Hirofumi Kogure Mitsuhiro Fujishiro Department of Gastroenterology Toyoshima Endoscopy ClinicTokyo 157-0066Japan Department of Gastroenterology and Hepatology International University of Health and WelfareNarita HospitalChiba 286-8520Japan Department of Pathology Pathology and Cytology Laboratory JapanTokyo 166-0003Japan Department of Gastroenterology Graduate School of MedicineThe University of TokyoTokyo 113-8655Japan Department of Gastroenterology Sakitani Endoscopy ClinicChiba 275-0026Japan Department of Gastroenterology The Fraternity Memorial HospitalTokyo 130-8587Japan Department of Surgical Oncology The University of TokyoTokyo 113-8655Japan Department of Internal Medicine Umegaoka Ekimae ClinicTokyo 154-0022Japan

BACKGROUND Accurate diagnosis of colorectal premalignant polyps,including adenomas,is vital in clinical *** To investigate the diagnostic yields of novel findings of brown slits for *** Patients who underwent colonoscopy at the Toyoshima Endoscopy clinic were *** sized≥5 mm suspected of adenomas or clinically significant serrated polyps were included in the *** defined the surface structures of colorectal polyps,which were brown curves inside and along the tubular glands identified using a combination of a new X1 system(Olympus Corporation)and a conventional magnifying colonoscope with non-staining narrow band imaging(NBI),as brown *** brown slits corresponded to slit-like lumens on endocytoscopy and histological crypt openings of an *** evaluated the diagnostic performance of brown slits for *** A total of 108 Lesions from 62 patients were *** average age was 60.4 years and 41.9%were *** mean polyp size was 7.45±2.83 ***-seven lesions were positive for brown *** diagnosis comprised 59 low-grade tubular adenomas,16 sessile serrated lesions,and 33 hyperplastic *** 59 adenomas,56(94.9%)were positive for brown *** 16 sessile serrated lesions,0(0%)was positive for brown *** 33 hyperplastic polyps,1(3.0%)was positive for brown *** sensitivity,specificity,and accuracy of brown slits for adenoma were 94.9%,98.0%,and 96.3%,*** positive predictive value and negative predictive value of brown slits for adenoma were also excellent for 98.2%,and 94.1%,*** Brown slits on conventional magnifying endoscopy with non-staining NBI using the X1 system were useful for diagnosing colorectal *** new endoscopy system could be examined using new standards.

关键词： Adenoma Colonoscopy Narrow band imaging Magnifying endoscopy X1 Serrated polyp Colorectal neoplasm Endocytoscopy

Oral Health Management of Three Head and Neck Cancer Patients Performed by Dental Hygienists

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Health 2023年第12期15卷 1402-1414页

作者： Aiko Hoshiai Meiko Oki Taiji Hoshiai Toshiaki Iida Yuka I. Sumita Shigeru watanabe Department of Pediatric Dentistry/Special Needs Dentistry Graduate School of Medical and Dental Sciences Tokyo Medical and Dental University Tokyo Japan Department of Oral Health Sciences School of Health Sciences Meikai University Chiba Japan Department of Basic Oral Health Engineering Graduate School of Medical and Dental Sciences Tokyo Medical and Dental University Tokyo Japan Department of Dentistry Tokyo Metropolitan Fuchu Medical Center for the Disabled Tokyo Japan TI Dental clinic Tokyo Japan Division of General Dentistry 4 The Nippon Dental University Hospital Tokyo Japan Tokyo medical and Dental University (TMDU) Tokyo Japan

Introduction: Oral health management is often difficult in patients after surgical tumor resection and/or radiotherapy due to defects, bulky flaps, limitation of tongue movement, and trismus. In addition, patients who have undergone radiotherapy have serious disabilities such as oral mucositis, mucosal weakening, soft tissue fibrosis, salivary gland disorder, and osteoradionecrosis. Dental hygienists must understand the characteristics of patients after surgical tumor resection and/or radiotherapy. In this report, the oral health management of three patients after maxillectomy, mandibulectomy, and radiotherapy was shown. Case Description: Case 1: A 53-year-old male patient visited our clinic after chemotherapy, radiotherapy, and partial maxillectomy for cancer of the right maxillary gingiva. Case 2: A 65-year-old male patient visited our clinic after radiotherapy for a right-sided tongue cancer, partial mandibulectomy of the right tongue to the oropharynx, a right-sided segmental mandibulectomy and a speech aid and a mandibular prosthesis were provided. Case 3: A 36-year-old female visited our clinic for radiotherapy for left-sided tongue cancer. Dental hygienists provided oral health management to the patients. In oral health management, it was suggested that intervention before cancer treatment, oral hygiene instructions tailored to patients’ symptoms, and frequent professional care are important. Conclusion: Oral health management by dental hygienists is extremely important for patients undergoing maxillofacial cancer treatment to maintain their quality of life in the long term.

关键词： Head and Neck Cancer Dental Hygienist Oral Health Management Maxillectomy Mandibulectomy Interstitial Radiotherapy

clinical Characteristics of Japanese Type 2 Diabetic Patients Responsive to Sitagliptin

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Journal of Diabetes Mellitus 2014年第3期4卷 172-178页

作者： Kouichi Inukai Takumi Hirata Takashi Sumita Masaki watanabe Yuichi Ikegami Daisuke Ito Susumu Kurihara Nobuyuki Yasukawa Jiro Morimoto Nobuki Takata Kenta Kanazawa Tamotsu Neda Yoshikazu Sumitani Kiyoaki Inoue Yuichi Noguchi Toshio Hosaka Hitoshi Ishida Shigehiro Katayama Department of Internal Medicine Saitama Social Insurance Hospital Saitama Japan Division of Endocrinology and Diabetes Saitama Medical University Saitama Japan Foundation for Biomedical Research and Innovation Hyogo Japan Sakado Central Hospital Saitama Japan Third Department of Internal Medicine Division of Diabetes Endocrinology and Metabolism Kyorin University School of Medicine Tokyo Japan watanabe medical clinic Hiroshima Japan

Japanese type 2 diabetic patients were treated with sitagliptin to evaluate the efficacy of this agent, and also to investigate the clinical characteristics of those who responded to sitagliptin. In total, 1001 diabetic patients, inadequately controlled (HbA1c ≥ 6.5%) with oral hypoglycemic agents (OHA) other than DPP-4 inhibitors or with diet and exercise only, were enrolled. We added 50mg of sitagliptin to the therapeutic regimens of 410 patients including 68 OHA naive patients, while the other 591 patients were switched from a single OHA to 50 mg of sitagliptin. After 6 months, glycemic control was significantly improved due to both reduced insulin resistance, as demonstrated by a significant HOMA-R reduction, and recovery of pancreatic β cell function, as assessed by HOMA-β and the proinsulin/insulin (PI/I) ratio. In the bivariable analysis, a good response, defined as an HbA1c reduction during the 6 months of at least 0.9%, was associated with high HbA1c and PI/I at baseline and combination treatments with sulfonylurea, biguanide and α-glucosidase inhibitors, but not with obesity. On the other hand, in the multivariable regression analysis, only high baseline HbA1c and combination treatment with anα-glucosidase inhibitor were significantly associated with a good response to sitagliptin. In patients with type 2 diabetes, the addition of sitagliptin or switching from another OHA to this agent achieved an HbA1c reduction without overloading β cells. In particular, we suggest that a good response to sitagliptin can be expected when this agent is combined with an α-glucosidase inhibitor (UMIN No. #000014157).

关键词： Sitagliptin Type 2 Diabetes DPP-4 Inhibitors