Role of prucalopride, a serotonin (5-HT4) receptor agonist, for the treatment of chronic constipation

Constipation affects up to a quarter of the population in developed countries and is associated with poor quality of life and significant economic burden. Many patients with chronic constipation are dissatisfied with current therapy due to lack of long-term efficacy or side effects. Previous nonselective 5-hydroxytryptamine receptor 4 (5-HT4) agonists have been associated with significant interactions with other receptors (5-HT1B, 5-HT1D, and 5-HT2B for tegaserod; hERG for cisapride), leading to adverse cardiovascular events resulting in withdrawal of these drugs from the market. Prucalopride is a novel gastrointestinal prokinetic agent. It acts as a high affinity, highly-selective 5-HT4 agonist. Its efficacy in patients with chronic constipation has been demonstrated in several phase II and phase III clinical trials showing significant improvements in bowel transit, bowel function, gastrointestinal symptoms, and quality of life, with benefit maintained for up to 24 months in open label, multicenter, follow-up studies. Prucalopride’s high selectivity for the 5-HT4 receptor may explain its favorable safety and tolerability profiles, even in elderly subjects with stable cardiovascular disease. Prucalopride is a well tolerated and efficacious prokinetic medication that should enhance the treatment of chronic constipation unresponsive to first-line treatments

Long-term Ultrasonographic Follow-up Study of Gastric Motility in Patients with Functional Dyspepsia

Although patients with functional dyspepsia complain of epigastric symptoms, the relation between these symptoms and gastric motility remains controversial. There are few reports on the clinical course of functional dyspepsia, including changes in gastric motility, observed over a considerably long period. We conducted a study to examine association between changes in symptoms and changes in ultrasonographically evaluated gastric motility over a long-term follow-up period in patients with functional dyspepsia. Forty patients (18 men, 22 women; mean age, 53.7 years) with functional dyspepsia were followed up by medical interview, physical examination, endoscopy, and ultrasonography for gastric motility. Follow-up ranged from 1.0 to 7.8 years (mean, 3.0 years). Ultrasonographic evaluation of gastric motility included gastric emptying rate and antral contractions. During the follow-up period, patients were treated with proton pump inhibitors, H2-blockers, or prokinetics. Symptoms improved in 21 patients (group A), but symptoms persisted or worsened in 19 patients (group B). There were no significant differences in clinical characteristics between the two groups. Gastric motility improved in group A but not in group B. In conclusion, improved gastric motility appears to correspond to and may explain improved symptoms in some patients with functional dyspepsia

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