Comparison of Efficacy and Safety between Mosapride and Acotiamide for Japanese patients with Functional Dyspepsia

　Background: 5-HT4 agonists (mosapride) and acetylcholine esterase inhibitor (acotiamide) are prokinetics used to treat functional dyspepsia (FD). However, to date, there has been no direct comparative study between them. The aim of this study was to compare the drugs’ efficacy and safety and to determine their predictive biomarkers.　Methods: The present study was a prospective, randomized, open-labeled, and crossover trial in Japanese FD patients. FD was diagnosed using Rome IV. We performed upper gastrointestinal (GI) endoscopy, GI symptom rating scale, and 8-item Short-Form Health Survey to evaluate the presence of GI disorders, GI symptoms, and quality of life (QOL), respectively. Responders were defined when reporting at least a 40% improvement of the GSRS scores from their baseline.　Results: In total, 60 Japanese FD patients were randomly assigned to the acotiamide preceding group (n = 30) or mosapride preceding group (n = 30), and 51 patients were finally analyzed. Following treatment with both mosapride and acotiamide, GI symptoms and QOL scores improved significantly. The responder rates of mosapride and acotiamide were 37% and 33%, respectively. No severe adverse clinical event developed. The prevalence of H. pylori eradication history was significantly lower in the mosapride responder group than in the nonresponder group (45.9% vs. 14.2%, p = 0.03).　Discussion: Mosapride and acotiamide had similar effects on GI symptoms in FD patients in the absence of severe adverse events. H. pylori infection might impact in the pathogenesis of functional dyspepsia. Further investigation is needed to clarify the difference between mosapride and acotiamide

The role of Kyoto classification in the diagnosis of Helicobacter pylori infection and histologic gastritis among young subjects in Japan

　BACKGROUND AND AIM: Helicobacter pylori (H. pylori) infection induces inflammation of the gastric mucosa and leads to erosions, gastro-duodenal mucosa atrophy, and intestinal metaplasia. The Kyoto classification diagnoses H. pylori infection via endoscopic findings. We aimed to clarify the role of the Kyoto classification in diagnosing H. pylori infection and histologic gastritis in young Japanese individuals.　METHODS: From1031 consecutive subjects aged ≤29 years who underwent esophagogastroduodenal endoscopy at our two hospitals from 2010 to 2017, 220 were selected for participation in the present study. Endoscopic biopsy specimens from the antrum and corpus were used to investigate H. pylori infection and histology. Endoscopic and histological interpretations were based on the Kyoto classification and updated Sydney System. H. pylori infection was confirmed by histology and Giemsa or Gimenez staining.　RESULTS: Endoscopic findings were normal in 103 cases. Atrophy was found in 56 cases; diffuse redness, in 45 cases; nodularity, in 38 cases; and mucosal swelling, in 34 cases. The infection rate was 30.9% (68/220). In total, 67 subjects with H. pylori -positive endoscopic findings and confirmed as H. pylori -positive had histologic gastritis of the antrum and corpus. In contrast, of 153 subjects with H. pylori -negative endoscopic findings only 1 was subsequently confirmed to be H. pylori positive. Among the 67 subjects with H. pylori -positive endoscopic findings, 23 (34.3%) presented with histological atrophic gastritis of the corpus and 6 (9.0%) with intestinal metaplasia.　CONCLUSIONS: Our findings show that H. pylori infection is strongly associated with endoscopic and histologic gastritis in young subjects and both H. pylori infection and histologic gastritis can be evaluated endoscopically based on the Kyoto classification. Furthermore, prompt H. pylori eradication may prevent gastric cancer development given the high prevalence of atrophic gastritis and intestinal metaplasia in young Japanese individuals

Clinicopathological features of advanced gastric cancer discovered after Helicobacter pylori eradication

　Helicobacter pylori infection is closely associated with gastric cancer, and its eradication is expected to prevent gastric cancer. However, gastric cancer is often detected discovered after eradication therapy for H. pylori infection. We aimed to investigate the endoscopic and clinical features of advanced gastric cancer after H. pylori eradication.　We retrospectively investigated tumor location, macroscopic and histological type, endoscopic gastric mucosal atrophy (using the Kimura-Takemoto classification), and the interval between eradication and detection of gastric cancer.　Nine patients (five males; mean age, 65.3 years [range, 44-79 years]), histologically diagnosed with advanced gastric cancer after successful H. pylori eradication between April 2003 and December 2018, were enrolled in this study.　In all cases, the cancer was located in the middle-to-upper portion of the stomach. With respect to macroscopic type, six cases were ulcerative, two were scirrhous, and one was polypoid. Histologically, all cancers were poorly or moderately differentiated adenocarcinomas. Endoscopic mucosal atrophy was mild in two cases, moderate in two cases, and severe in five cases. Two cases of scirrhous tumors developed from mild mucosal atrophy. Moreover, the tumor was detected within 36 months after H. pylori eradication in six patients (maximum: 120 months, mean: 38.7 months).　Our data demonstrated that post-eradicated advanced gastric cancers were located in the middle-to-upper portion of the stomach and were mainly ulcerative, poorly or moderately differentiated adenocarcinoma. More than half of the patients exhibited severe mucosal atrophy

A case of synchronous triple cancer of the esophagus, stomach, and colon detected by using gastrointestinal screening endoscopy

　In recent years, the detected number of multiple primary malignant tumors (MPMTs) in the gastrointestinal tract has been increasing with the advancement of gastrointestinal endoscopic equipment and the spread of endoscopic screening.　Here, we report a case of synchronous MPMTs of the esophagus, stomach, and colon detected by means of gastrointestinal screening endoscopy. The patient was a 67-year-old man who regularly visited the medical clinic for hypertension. He had a history of alcohol consumption (sake index: 250, with alcohol flushing syndrome) and smoking (Brinkman index: 800), and a family history of cancer (his father had gastric cancer).　At the medical clinic, he underwent gastrointestinal endoscopy for screening purposes. Prior observation with linked-color imaging (LCI), a type of image-enhanced endoscopy (IEE), revealed an irregular depressed lesion in the mid-esophagus. Simultaneously, an irregular, highly deformed depressed lesion and a small depressed lesion were detected on the incisura of the lesser curvature and the lesser curvature of the antrum, respectively. The esophageal lesion was identified as squamous cell carcinoma and both gastric lesions were identified as well-differentiated adenocarcinoma.　The patient was referred to our hospital for further examination and treatment for esophageal and gastric cancer. Subsequent colonoscopy revealed a well-defined, ulcerative tumor in the transverse colon. First, endoscopic submucosal dissection was performed for the esophageal lesion, followed by laparoscopy-assisted distal gastrectomy with D1+ lymph-node dissection and transverse colectomy with D2 lymph-node dissection for the gastric and colorectal lesions, respectively. Histopathologically, the main gastric and colonic tumors were in advanced stages; fortunately, the esophageal cancer was an early-stage lesion (7 × 5 mm, 0-IIc, pT1a-LPM, INFa, ly0, v0, pCurA), which has a much better prognosis than advanced esophageal cancer.　In patients with multiple cancer risk factors (alcohol consumption, smoking, and family history), it is important to consider the possibility of MPMTs. Furthermore, upper gastrointestinal observation combined with IEE, such as LCI, may be useful in the early detection of lesions

同時性4重複癌の一例

近年,癌の診断技術の進歩や治療成績の向上に伴い重複癌の報告が増加しているが,同時性4重複癌の頻度は0.21%と稀である.超音波検査によるスクリーニングが診断に有用であった同時性4重複癌の一例を報告する.症例は69歳の男性で肝障害と高血圧で定期通院中であった.増大する無痛性頸部腫瘤を自覚し頸部超音波検査を施行し,転移性リンパ節腫大を疑い,同日に腹部超音波検査を行った.その結果,進行胃癌と進行大腸癌を疑い,消化管精査を開始した.精査の結果,中咽頭癌,食道癌,胃癌,直腸癌の同時性4重複癌であった.最も進行度の高い中咽頭癌から治療を開始し,現在外来通院中であるが,経過は良好である.1990年から2013年の間で医中誌による検索では同時性4重複癌の報告は自験例を含めて15例に過ぎない.その15例で検討を行うと男性に多く,罹患臓器は胃癌と食道(8.8%),または胃癌と直腸の重複(6.9%)と消化管領域での重複を多く認めた.重複癌の発生要因としては飲酒や喫煙などの嗜好品,遺伝的要因が報告されている.飲酒習慣については飲酒後の顔面の紅潮(フラッシャー)は発癌リスクが有意に高まるとされ,本症例でもBrinkman Index 1350,Sake Index 180と高値であり,更にフラッシャーであり複数のリスク因子を認めた.遺伝的要因については家族性大腸腺腫症やLynch症候群での多臓器癌の発症が知られているが,本症例では病理標本での検討の結果,その可能性は否定的であった.癌の治療方針決定においては,進行度の評価が重要となるため,全身のスクリーニングが必要であるが,超音波検査は非侵襲かつ放射線被曝もないことから,スクリーニングに適した検査法と考えられた.According to the recent advancement in diagnosis technique for cancers, the incidence of patients with cancer has been increasing. However, cases with synchronous quadruple cancers are rarely found. In this paper, we report a case of synchronous quadruple cancers located in the pharynx, esophagus, stomach and rectum. A 69-year-old man complained of swelling in the cervical lymph nodes, suspected to be metastasis by cervical ultrasonographic examination. Additionally, advanced gastric cancer and advanced rectal cancer were suspected via an abdominal ultrasonography (US). Thereafter, subsequent detailed examinations revealed the quadruple cancers, including advanced middle pharyngeal cancer, early-stage esophageal cancer, advanced gastric cancer and advanced rectal cancer. Chemoradiation therapy was performed for pharyngeal cancer as a neoadjuvant treatment because it was at the most advanced clinical stage. The patient had a good clinical course after the treatment. In Japan, we identified 14 case reports about synchronous quadruple cancers through the Japan Medical Abstracts Society database between the years 1990 to 2013. Summarizing all these cases, including our case, showed the following findings: male (13 cases) were predominant with a combination of gastric cancer and esophageal cancer (8.8%), or the combination of gastric cancer and rectal cancer (6.9%) were also common. Furthermore, cigarette smoking and alcohol consumption were considered the major risk factors for patients presenting with multiple cancers. Our patient was found to have both risks such as Brinkman Index 1350 and Sake Index 180. The treatment order for patients with cancer should be determined by its clinical stage. Screening examinations for checking metastasis or other organic diseases are important. Ultrasonography (US) is noninvasive and free from radiation exposure and it is a useful modality for patients with cancer

含糖酸化鉄注射液の長期投与でFGF23関連低リン血症性骨軟化症を来たしたクローン病の１例

症例は50歳代，男性．クローン病で２年前に右半結腸切除術，小腸部分切除を施行．術後に他院にてアダリムマブを導入され，クローン病は臨床的寛解の状態であった．４か月前より下肢を中心とした疼痛が出現した．アダリムマブによる薬剤起因性ループスあるいは腸炎性関節炎を疑い，２か月前よりアダリムマブ投与を中止し，プレドニゾロンの内服を開始するも改善を認めなかった．血液検査にて，低リン血症と高アルカリフォスファターゼ血症を認め，精査治療目的で当院に紹介入院となった．骨塩定量検査にて骨密度の低下を，骨シンチグラフィーで疼痛を認める骨への多発取り込みを認め，骨軟化症と診断した．血清のfibroblast growth factor 23（FGF23）が175pg/ml と高値であり，入院前まで定期的に使用されていた含糖酸化鉄注射液による，FGF23関連低リン血症性骨軟化症と診断した．含糖酸化鉄注射液投与を中止し，リン製剤とビタミンD 製剤の投与を開始したところ，徐々に低リン血症と高アルカリフォスファターゼ血症の改善を認めた．その後の経過は良好で，FGF23値は徐々に低下を示し，下肢を中心とした疼痛は軽快し，退院した．長期的に含糖酸化鉄注射液を投与する場合は，FGF23関連低リン血症の早期発見のため，血中リン濃度を定期的に測定する必要がある．The case is a man in his 50s. He underwent operations of right half colon resection and small intestine segmental resection due to Crohn’s disease two years ago. After surgery, Adalimumab was introduced in other hospital, and he was a state of the clinical remission in Crohn’s disease. The sharp pain mainly on lower limbs develops from four months ago. We doubted drug origin-related lupus with Adalimumab or enteritis-related joint pain. Therefore, we stopped Adalimumab injection and started internal use of the prednisolone, however the symptoms did not improve and had continued for two months.Laboratory test showed hypophosphatemia and hyperphosphatasemia and then he was transported to our hospital. Bone mineral quantity showed bone salt decrease and bone scan showed increased uptakes in multiple bones. Fibroblast growth factor23 (FGF23) of the serum was high (175pg/ml), and we diagnosed him FGF23-mediated hypophosphatemic osteomalasia induced by prolonged administration of saccharated ferric acid.Saccharated ferric acid has regularly been used until hospitalization. After stopping the ferric acid injection, and taking phosphorus and vitamin D, hypophosphatemia and hyperphosphatasemia was gradually improved. FGF23 level gradually reduced, and the sharp pain mainly on lower limbs was relieved, and it became a discharge. Regular measurement of serum phosphorus concentration is necessary for early detection of the FGF23-related hypophosphatemia in patients with long term use of saccharated ferric acid