Clinicopathological Characteristics of Everolimus-Associated Interstitial Lung Disease: A Single-Center Consecutive Analysis.

BACKGROUND: Everolimus, a mammalian target of rapamycin inhibitor used as an antineoplastic drug, is associated with a remarkably high incidence of interstitial lung disease (ILD). The clinical and pathological characteristics of ILD caused by everolimus have not been thoroughly investigated; therefore, we aimed to elucidate the features of everolimus-associated ILD. METHODS: We retrospectively reviewed the medical records of patients who received everolimus for cancer treatment at our hospital. Patient backgrounds were compared between the ILD and non-ILD groups. Chest computed tomography (CT), changes in biomarkers, and lung histopathological features were analyzed for ILD cases. RESULTS: Sixty-six patients were reviewed, and ILD developed in 19. There were no differences in patient demographics between the ILD and non-ILD groups. The severity of ILD was grade 1 (G1) in 9 and grade 2 (G2) in 10 cases. Chest CT showed organizing pneumonia (OP) or a hypersensitive pneumonia pattern. The levels of lactate dehydrogenase, C-reactive protein, Krebs von den lungen-6, and surfactant protein-D (SP-D) at the onset of ILD were significantly higher than those at baseline. Analysis of G1 and G2 ILD subgroups showed a higher SP-D levels in the G2 subgroup. Five patients underwent lung biopsies; all specimens demonstrated alveolitis with lymphocytic infiltration and granulomatous lesions, and some had OP findings. CONCLUSIONS: Everolimus-associated ILD is mild and has a favorable prognosis. Patients with symptomatic ILD were more likely to have higher SP-D levels than those with asymptomatic ILD. Granulomatous lesions are an important pathological feature of everolimus-associated ILD.

A Proposed New Clinical Classification of Metastatic Gastric Cancer: Pyloric and Antral Gastric Cancer.

BACKGROUND: We aimed to classify metastatic pyloric/antral gastric cancer in terms of macroscopic morphology and metastatic form. METHODS: Thirty-eight patients with pyloric/antral gastric cancer were included in the study. Patients were classified according to a combination of Borrmann classification type and metastatic type, and the clinicopathological characteristics of each group were compared. RESULT: Of the 38 patients, 33 (type II: 9 and type III: 24) (87%) had ulcerative gastric cancer. Ulcerative gastric cancer was classified into four groups: lymphatic only group (L+H-P-), lymphatic + hematogenous group (L+H+P-), disseminated ± lymphatic group (L±H-P+), and lymphatic + hematogenous + disseminated group (L+H+P+). In the L+H-P- group, all patients had bulky lymph nodes and serum levels of both carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were high; the condition of patients was good, and the therapeutic response was good. In the L+H+P- group, metastases other than liver metastases were rare, and serum CEA levels were high. In the L±H-P+ group, the predominant histological type was signet ring cell carcinoma; both serum CEA and CA19-9 levels were low. Patients in the L+H+P+ group had higher serum CA19-9 levels and were more prone to hematogenous metastasis to various organs; these patients had worse patient status and lower treatment response. Gastric cancer other than ulcerative type was only detected in five patients (type V: 3, type IV: 1, type I: 1). CONCLUSION: Classification by a combination of macroscopic and metastatic form in pyloric/antral metastatic gastric cancer might be useful for diagnosis and treatment.

Relationship between gastroesophageal reflux disease (GERD) and constipation: laxative use is common in GERD patients.

BACKGROUND: The relationship between gastroesophageal reflux disease (GERD) and constipation has not yet been examined in Japan. We herein analyzed the use of laxatives by GERD and non-GERD patients to clarify the relationship between GERD and constipation. METHODS: This was a retrospective observational study designed to examine the use of laxatives by GERD and non-GERD patients. A total of 118 patients (mean age 69.7 years, 50 males) with reflux esophagitis (RE) and non-erosive reflux disease (NERD) who received maintenance acid-suppressive therapy for more than 1 year were included in the GERD group (83 RE patients, 35NERD patients). Similarly, 61 patients (mean age 69.4 years, 28 males) who received regular acid-suppressive therapy for reasons other than GERD were included in the non-GERD group. We also investigated demographic factors associated with the onset of GERD, including body mass index (BMI), age, and sex. RESULTS: The frequency of laxative use was significantly higher in the GERD group (38.1%) than in the non-GERD group (21.3%). No significant differences were observed in dose frequencies between the groups. The type of laxative used also did not significantly differ between the groups. Furthermore, no significant differences were noted in sex, age, or BMI between the groups. CONCLUSIONS: The use of laxatives was significantly more common in GERD patients than in non-GERD patients. The present results suggest that a relationship exists between GERD and constipation.

Readministration of Cancer Drugs in a Patient with Chemorefractory Metastatic Colorectal Cancer.

A 63-year-old woman was admitted to our institution for severe pain in her right lower abdomen caused by the perforation of cecal cancer. She underwent emergency surgery, from which she was diagnosed with cecal carcinoma with liver, lung, and lymph node metastases. As she was taking aspirin to prevent cerebral infarction, anti-vascular endothelial growth factor (receptor) antibody and regorafenib therapy were not used. Thus, we started a modified FOLFOX 6+cetuximab regimen. This first-line treatment initially achieved a partial response (PR), but she then developed progressive disease (PD) after 14 months. We changed the regimen to FOLFIRI, followed by trifluridine/tipiracil, but her progression-free survival periods were 2.7 months and 1 month, respectively. Although we cycled through the available array of standard cancer drugs, the patient showed a good performance status, and some benefit from treatment still seemed plausible. We readministered the 5-fluorouracil oral preparation S-1, which maintained stable disease (SD) for 7 months. After PD emerged, we readministered the anti-epidermal growth factor receptor (EGFR) antibody panitumumab for 7.5 months of SD. Finally, 39 months after her diagnosis, she died from rapidly progressing disease. However, her relatively long survival implies that readministering drugs similar to those used in previous regimens might benefit patients with metastatic colorectal cancer.

Multi-center clinical evaluation of streptozocin-based chemotherapy for advanced pancreatic neuroendocrine tumors in Japan: focus on weekly regimens and monotherapy.

PURPOSE: Streptozocin (STZ) is a key agent for treating advanced pancreatic neuroendocrine tumors (pNET). Most STZ regimens for pNET are daily and also include 5-fluorouracil (5FU), whereas STZ monotherapy and weekly regimens have also been applied in daily practice in Japan. The present study aimed to evaluate responses to weekly regimens and to STZ monotherapy, and to identify a predictive marker of a response to STZ. METHODS: Clinical data regarding STZ-based chemotherapy for pNET were collected between 2015 and 2017 at 25 facilities. We analyzed the effects, safety, progression-free survival (PFS), and factors that correlate with responses to STZ. RESULTS: The overall objective response rate (ORR) of 110 patients who underwent STZ-based chemotherapy (monotherapy, 81.8%; weekly regimen 46.4%) was 21.8%, and PFS was 9.8 months. The ORR of weekly vs. daily regimens was 21.6 vs. 22.0% (P = 1.000), and that of monotherapy vs. combination therapy was 21.1 vs. 25.0% (P = 0.766). A Ki67 proliferation index (Ki67) of > 5% was a predictive marker of a response to STZ (P = 0.017), whereas regimen type, mono- or combination therapy, treatment line and liver tumor burden were not associated with responses. The frequencies of Grade ≥ 3 nausea and hematological adverse events were significantly lower for monotherapy than combination therapy (P = 0.032). CONCLUSIONS: The effects of weekly STZ monotherapy on pNET are comparable to those previously reported and the toxicity profile was acceptable. Ki67 > 5% was the sole predictive marker of an objective response.

Impact of Cyclooxygenase-2 1195 G-Carrier Genotype Associated with Intestinal Metaplasia and Endoscopic Findings Based on Kyoto Classification.

BACKGROUND/AIMS: We aimed to clarify whether cyclooxygenase-2 (COX-2) and microsomal prostaglandin E synthase-1 (mPGES-1) genotypes were associated with certain histological findings and endoscopical appearances based on Kyoto classification. METHODS: We enrolled 285 Helicobacter pylori-infected gastritis patients. Genotypes of COX-2 1195, COX-2 1290, mPGES-1, interleukin-1ß (IL-1ß) 511 and tumour necrosis factor-α (TNF-α) 308 were analyzed. Genotyping was performed by polymerase chain reaction. Endoscopic appearances and histological assessment were determined by using Kyoto classification, operative link on gastritic intestinal metaplasia assessment and the updated Sydney system. RESULTS: There was a significant (p = 0.027) relationship between the IL-1ß 511 C-carrier and histological gastric inflammation in H. pylori-infected gastritis patients. There was a significant (p = 0.009) correlation between the COX-2 1195 G-carrier genotype and histological intestinal metaplasia in the gastric antrum of H. pylori-infected gastritis patients and gastric xanthoma (p = 0.027). The COX-2 1195 G-carrier genotype was also significantly (p = 0.038) associated with the score of endoscopic intestinal metaplasia based on Kyoto classification. The mPGES-1 genotype was significantly (p = 0.002) associated with endoscopic swelling of area. CONCLUSION: Our results suggest that in Japan, there exists a significant correlation between the COX-2 1195 G-carrier genotype and intestinal metaplasia in histological and endoscopic findings based on Kyoto classification in H. pylori-infected gastric mucosa.

Epigastric pain syndrome accompanying pancreatic enzyme abnormalities was overlapped with early chronic pancreatitis using endosonography.

There was not available data about the overlap between functional dyspepsia (FD) and pancreatic diseases. We aimed to determine whether epigastric pain syndrome (EPS) accompanying with pancreatic enzyme abnormalities were associated with early chronic pancreatitis proposed by Japan Pancreas Society (JPS) using endosonography. We enrolled 99 consecutive patients presenting with typical symptoms of FD, including patients with postprandial distress syndrome (PDS) (n = 59), EPS with pancreatic enzyme abnormalities (n = 41) and EPS without pancreatic enzyme abnormalities (n = 42) based on Rome III criteria. Gastric motility was evaluated using the 13C-acetate breath test. Early chronic pancreatitis was detected by endosonography and graded from 0 to 7. The ratio of female patients among EPS patients (34/41) with pancreatic enzyme abnormalities was significantly (p = 0.0018) higher than the ratio of female EPS patients (20/42) without it. Postprandial abdominal distention and physical component summary (PCS) scores in EPS patients with pancreatic enzyme abnormalities were significantly disturbed compared to those in EPS patients without it. Interestingly, AUC5 and AUC15 values (24.85 ± 1.31 and 56.11 ± 2.51, respectively) in EPS patients with pancreatic enzyme abnormalities were also significantly (p = 0.002 and p = 0.001, respectively) increased compared to those (19.75 ± 1.01 and 47.02 ± 1.99, respectively) in EPS patients without it. Overall, 64% of EPS patients with pancreatic enzyme abnormalities were diagnosed by endosonography as having concomitant early chronic pancreatitis proposed by JPS. Further studies are warranted to clarify how EPS patients with pancreatic enzyme abnormalities were associated with early chronic pancreatitis proposed by JPS.

Effect of Antithrombotic Therapy and Long Endoscopic Submucosal Dissection Procedure Time on Early and Delayed Postoperative Bleeding.

BACKGROUND: Recent updated guidelines of the Japanese Society of Gastroenterology recommend the use of a single dose of antiplatelet agents in patients undergoing endoscopic submucosal dissection (ESD). However, the postoperative bleeding risk after gastric ESD associated with the continuation or interruption of antithrombotic therapy remains controversial. We aimed to evaluate whether certain factors including interrupted antithrombotic therapy could affect early and delayed post-ESD bleeding risk. METHODS: Three hundred sixty-four patients with gastric neoplasms were treated with ESD at our hospital between October 2005 and December 2012. Seventy-four patients with interrupted antithrombotic therapy were undertaken with ESD. Early and delayed postoperative bleeding patterns were estimated. Various clinical characteristics such as gender, age, tumor location, tumor size, ESD procedure time, platelet count, and comorbidity were evaluated. RESULTS: There was a significant difference (p = 0.042) in the ESD procedure time between the patients with postoperative bleeding and those without it. There was no significant difference in postoperative bleeding between the patients on antithrombotic therapy and not on it. Moreover, interrupted antithrombotic therapy and platelet count were significantly (p = 0.0461 and p = 0.0059, respectively) associated with early postoperative bleeding in multivariate analysis. In addition, in univariate analysis, ESD procedure time was significantly (p = 0.041) associated with delayed postoperative bleeding. CONCLUSIONS: Antithrombotic therapy and prolonged ESD procedure time were significantly associated with early and delayed postoperative bleeding, respectively.

Efficacy of Vonoprazan for Proton Pump Inhibitor-Resistant Reflux Esophagitis.

BACKGROUND: Vonoprazan (VPZ) is a novel potassium-competitive acid blocker that may be clinically beneficial for proton pump inhibitor (PPI)-resistant reflux esophagitis (RE). The aim of this study was to investigate the efficacies of VPZ therapy at 20 mg for 4 weeks in patients with PPI-resistant RE and VPZ maintenance therapy at 10 mg for 8 weeks in patients who have been successfully treated. METHODS: Subjects comprised 24 patients with PPI-resistant RE (Los Angeles classification grade A/B/C/D: 3/7/11/3). After confirming PPI-resistant RE by endoscopy, 20 mg VPZ was administered. Endoscopy was performed 4 weeks after the initiation of VPZ. Symptoms were evaluated using the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG). Maintenance therapy with 10 mg VPZ was performed and endoscopy was conducted after 8 weeks. RESULTS: In 21 (87.5%) out of 24 patients, esophageal mucosal breaks were successfully treated by 20 mg VPZ. The median FSSG score was significantly lower on days 1-7, 14, and 28 after the initiation of VPZ than before its administration. Maintenance therapy with 10 mg VPZ prevented the relapse of esophageal mucosal breaks in 16 (76.2%) out of 21 patients. CONCLUSION: VPZ was effective for most patients with PPI-resistant RE.

Clinical Complete Response from Chemotherapy in an Elderly Patient with Metastatic Gastric Cancer: A Case Report.

An 81-year-old man was admitted with upper abdominal pain and weight loss. Esophagogastroduodenoscopy revealed a large tumor located from the gastric angle to the body. Histological analysis of a biopsy revealed a moderately differentiated adenocarcinoma. Computed tomography revealed metastases in the liver and lung and the patient was subsequently diagnosed with metastatic advanced gastric cancer. He was treated with chemotherapy using S-1 (80 mg/m2) and cisplatin (CDDP) (60 mg/m2). Twenty-two months after chemotherapy, the gastric tumor, and the nodules in the liver and lung, had disappeared. We subsequently diagnosed a clinical complete response. The patient was treated with further S-1 monotherapy for 7 months after complete response assessment. He has lived for more than 7 years since the initial diagnosis without recurrence. Chemotherapy using S-1 and CDDP may be a potent strategy for improving survival in elderly patients with advanced gastric cancer.

Proton pump inhibitors are associated with lower gastrointestinal tract bleeding in low-dose aspirin users with ischaemic heart disease.

BACKGROUND: Impact of acid suppressants on lower gastrointestinal bleeding remains unclear in low-dose aspirin users; we aimed to investigate this relationship. METHODS: Retrospective cohort study of low-dose aspirin users who underwent coronary angiography for ischaemic heart disease in our institution between October 2005 and December 2006; patients were evaluated for upper or lower gastrointestinal bleedings within 3 years post-angiography. RESULTS: 538 patients were enrolled (males, 74.4%; mean age 67.4±10.6 years). Risk for upper gastrointestinal bleeding decreased with concomitant use of statins (HR, 0.37; 95% CI, 0.15-0.89), calcium channel blockers (HR, 0.29; 95% CI, 0.10-0.85), and histamine-2 receptor antagonists (HR, 0.26; 95% CI, 0.08-0.89). Concomitant use of proton pump inhibitors tended to decrease risk of upper gastrointestinal bleeding (HR, 0.27; 95% CI, 0.06-1.18). Risk for lower gastrointestinal bleeding increased with both concomitant use of warfarin (HR, 15.68; 95% CI, 4.43-55.53) and proton pump inhibitors (HR, 6.55; 95% CI, 2.01-21.32), but not with histamine-2 receptor antagonists. Hyperuricemia lowered risk for lower gastrointestinal bleeding (HR, 0.12; 95% CI, 0.02-0.88). CONCLUSIONS: In low-dose aspirin users, concomitant use of proton pump inhibitors increased lower gastrointestinal bleeding risk, independent from effects on upper gastrointestinal bleeding.

Leu72Met408 Polymorphism of the Ghrelin Gene Is Associated With Early Phase of Gastric Emptying in the Patients With Functional Dyspepsia in Japan.

BACKGROUND/AIMS: There are no available data about the relationship between ghrelin gene genotypes and early phase of gastric emptying in functional dyspepsia (FD) as defined by Rome III classification. METHODS: We enrolled 74 patients presenting with typical symptoms of FD and 64 healthy volunteers. Gastric motility was evaluated using the 13C-acetate breath test. We used Rome III criteria to evaluate upper abdominal symptoms and self-rating questionnaires for depression (SRQ-D) scores to determine status of depression. The Arg51Gln (346G->A), preproghrelin (3056T->C), Leu72Met (408C->A), Gln90Leu (3412T->A) and G-protein 3 (825C->T) polymorphisms were analyzed in the DNA from blood samples of enrolled subjects. Genotyping was performed by polymerase chain reaction. RESULTS: There was a significant relationship between the Gln90Leu3412 genotype and SRQ-D score in FD patients (P = 0.009). Area under the curve at 15 minutes (AUC15) value was significantly associated with the Leu72Met408 genotype (P = 0.015) but not with entire gastric emptying. CONCLUSIONS: The Leu72Met (408C->A) single nucleotide polymorphism was significantly associated with early phase of gastric emptying in FD patients. Further studies will be necessary to clarify the association between ghrelin gene single nucleotide polymorphisms and early phase of gastric emptying in FD patients.

Impact of eating attitude and impairment of physical quality of life between tertiary clinic and primary clinic functional dyspepsia outpatients in Japan.

BACKGROUND/AIMS: There is no available data on factors associated with healthcare-seeking behavior for functional dyspepsia (FD) symptoms at ei-ther tertiary or primary clinics in Japan. Therefore, we aimed to compare clinical symptoms and life styles such as sleep dis-orders and eating attitude in FD patients visiting general practitioners at primary clinics with those consulting gastro-enterologists at tertiary clinics to clarify healthcare-seeking patterns in Japanese patients. METHODS: Fifty-one FD outpatients in a tertiary clinic (college hospital), 50 FD outpatients visiting primary clinics and 50 healthy volunteers were enrolled. Clinical symptoms, quality of life, sleep disorders, eating attitude and anxiety were estimated using the Gastroin-testinal Symptom Rating Scale (GSRS), Social Functioning-8 (SF-8) test, Pittsburg Sleep Quality Index (PSQI) test and State-Trait Anxiety Inventory (STAI) for FD outpatients and healthy volunteers. RESULTS: FD outpatients exhibited higher mean scores of GSRS than healthy volunteers. The SF-8 physical component summary scores in the tertiary clinic group were significantly lower than those in the primary clinic group. GSRS scores were significantly (P < 0.001, P = 0.002) associated with global PSQI scores in FD outpatients as well as with STAI-trait scores (P = 0.006, P = 0.001) compared to healthy volunteers. The frequency of eating between meals in the primary clinic group was significantly (P < 0.05) higher than that in the tertiary clinic group. CONCLUSIONS: It may be important for clarification of healthcare-seeking behavior to determine the difference in both impairment of physical quality of life and eating attitudes between tertiary clinic and primary clinic FD outpatients in Japan.(J Neurogastroenterol Motil 2014;20:506-515).

[A case of multiple primary small intestinal adenocarcinomas].

A 62-year-old woman, with a past history of long-term non-steroidal anti-inflammatory drug use and gastric ulcer, was hospitalized for intestinal obstruction in April 2012. Two stenoses were identified in the ileum in association with small intestinal ulcers, and she underwent partial resection of the small intestine. Histologically, the two lesions were poorly differentiated adenocarcinomas; metastatic small intestinal cancer was suspected, but whole body examination revealed no other lesions. The final diagnosis was multiple primary small intestinal malignancies, necessitating additional resection of the small intestine in July. We report this case to raise awareness among physicians of the possibility of primary small intestinal cancer in patients with multiple small intestinal stenoses.

Impact of sleep disorders, quality of life and gastric emptying in distinct subtypes of functional dyspepsia in Japan.

BACKGROUND/AIMS: The association between clinical symptoms, gastric emptying, quality of life and sleep disorders in distinct functional dyspepsia (FD) patients has not been studied yet in detail. METHODS: We enrolled 79 FD patients (postprandial distress syndrome [PDS], n = 65; epigastric pain syndrome [EPS], n = 47; EPS-PDS overlap, n = 33) and 44 healthy volunteers. Gastric motility was evaluated. We used Rome III criteria to evaluate clinical symptoms and State-Trait Anxiety Inventory (STAI) scores to determine anxiety status. Sleep disorder was evaluated using the Pittsburgh Sleep Quality Index scores. RESULTS: There were no significant differences in age, sex and Helicobacter pylori positivity between FD subtypes and healthy volunteers. The scores of Glasgow dyspepsia severity scores (GDSS), SF-8 and Pittsburgh Sleep Quality Index (PSQI) in distinct subtypes of FD patients were significantly different from those in healthy volunteers. However, there were not significant differences in these scores, Tmax and T1/2 among 3 subtypes of FD patients. PSQI score was significantly (P = 0.027, P = 0.002 and P = 0.039, respectively) associated with GDSS among EPS, PDS and EPS-PDS overlap patients. In addition, 8-item short form health survey (SF-8; Physical Component Score and Mental Component Score) was significantly associated with global PSQI score in PDS and EPS-PDS overlap patients. In contrast, SF-8 (Mental Component Score) only was significantly linked to global PSQI score in EPS patients. CONCLUSIONS: Prevalences for sleep disorders, gastric motility and quality of life in 3 subtypes of FD patients were similar levels. In PDS and EPS-PDS overlap patients, SF-8 was significantly associated with global PSQI score.

Apurinic/apyrimidinic endonuclease-1 is associated with angiogenesis and VEGF production via upregulation of COX-2 expression in esophageal cancer tissues.

Apurinic/apyrimidinic endonuclease-1 (APE-1) is a key enzyme responsible for DNA base excision repair and is also a multifunctional protein such as redox effector for several transcriptional factors. Our study was designed to investigate APE-1 expression and to study its interaction with cyclooxygenase (COX)-2 expression and VEGF production in the esophageal cancer. The expression of APE-1, COX-2, monocyte chemoattractant protein (MCP)-1, CC-chemokine receptor (CCR)2, and VEGF were evaluated by immunohistochemistry in 65 human esophageal squamous cell carcinoma (ESCC) tissues. Real-time PCR and Western blotting were performed to detect mRNA and protein expression of APE-1 and p-signal transducer and activator of transcription 3 (STAT3) expression in MCP-1-stimulated ESCC cell lines (KYSE 220 and EC-GI-10). siRNA for APE-1 was treated to determine the role of APE-1 in the regulation of COX-2 expression, VEGF production, and antiapoptotic effect against cisplatin. In human ESCC tissues, nuclear localization of APE-1 was observed in 92.3% (60/65) of all tissues. There was a significant relationship (P = 0.029, R = 0.49) between nuclear APE-1 and cytoplasmic COX-2 expression levels in the esophageal cancer tissues. In KYSE 220 and EC-GI-10 cells, MCP-1 stimulation significantly increased mRNA and protein expression of APE-1. Treatment with siRNA for APE-1 significantly inhibited p-STAT3 expression levels in MCP-1-stimulated cells. Furthermore, treatment of siRNA for APE-1 significantly reduced COX-2 expression and VEGF production in MCP-1-stimulated esophageal cancer cell lines. Treatment with APE-1 siRNA significantly increased apoptotic levels in cisplatin-incubated KYSE 220 and EC-GI-10 cells. We concluded that APE-1 is overexpressed and associated with COX-2 expression and VEGF production in esophageal cancer tissues.

Impact of coexisting irritable bowel syndrome and non-erosive reflux disease on postprandial abdominal fullness and sleep disorders in functional dyspepsia.

BACKGROUND/AIMS: The association between clinical symptoms and sleep disorders in functional dyspepsia (FD)-overlap syndrome has not been studied in detail. METHODS: The subjects were 139 patients with FD, 14 with irritable bowel syndrome (IBS), 12 with nonerosive reflux disease (NERD), and 41 healthy volunteers. Gastric motility was evaluated with the (13)C-acetate breath test. We used Rome III criteria to evaluate upper abdominal symptoms, and Self-Rating Questionnaire for Depression (SRQ-D) scores to determine depression status. Sleep disorders were evaluated with Pittsburgh Sleep Quality Index (PSQI) scores. RESULTS: There were no significant differences in age, body-mass index, alcohol intake, and smoking rate between patients with FD alone and those with FD-overlap syndrome. The postprandial abdominal fullness score in patients with FD-NERD-IBS was significantly greater than that in patients with FD-NERD overlap syndrome (p<0.001) or FD alone (p<0.001). The score for the feeling of hunger in patients with FD-NERD-IBS was significantly greater than that in patients with FD alone (p=0.0025), FD-NERD overlap syndrome (p=0.0088), or FD-IBS overlap syndrome (p=0.0057). The heartburn score in subjects with FD-NERD-IBS overlap syndrome was significantly greater than that in subjects with FD alone (p=0.0035) or FD-IBS overlap syndrome (p=0.0026). The Tmax in patients with FD-overlap syndrome or FD alone was significantly higher than that in healthy volunteers. The Pittsburgh Sleep Quality Index score in subjects with FD-NERD-IBS overlap syndrome was significantly greater than that in subjects with FD alone. CONCLUSION: Symptom scores, such as those for postprandial abdominal fullness, heartburn, and the feeling of hunger, in patients with FD-overlap syndromes are significantly greater than those in patients with FD alone. Further studies are necessary to clarify whether various symptoms are related to sleep disorders in patients with FD-NERD-IBS overlap syndrome.

The preproghrelin 3056 TT genotype is associated with the feeling of hunger and low acylated ghrelin levels in Japanese patients with Helicobacter pylori-negative functional dyspepsia.

OBJECTIVE: An impairment of gastric motility is strongly associated with the pathophysiology of functional dyspepsia (FD). Plasma ghrelin is one of the key molecules linked to gastric motility. Therefore, this study aimed to evaluate whether ghrelin (GHRL) gene polymorphisms are associated with clinical symptoms, the plasma ghrelin levels and gastric emptying in patients with FD as defined by the Rome III classification. METHODS: We enrolled 74 Helicobacter pylori-negative patients presenting with typical symptoms of FD (epigastric pain syndrome (EPS), n=23; postprandial distress syndrome (PDS), n=51) and 102 healthy volunteers. Gastric motility was evaluated according to the Tmax value and T1/2 using the (13)C-acetate breath test. We used the Rome III criteria to evaluate upper abdominal symptoms and SRQ-D scores to determine the depression status. The Arg51Gln(346G->A), preproghrelin3056T->C, Leu72Met(408C->A) and Gln90Leu(3412T->A) polymorphisms were analyzed in DNA in blood samples obtained from the enrolled subjects. Genotyping was performed using polymerase chain reaction. RESULTS: There was a significant relationship (p=0.048) between the preproghrelin 3056TT genotype and the serum levels of acylated ghrelin in the H. pylori-negative FD patients. The preproghrelin 3056TT genotype was significantly (p=0.047) associated with the feeling of hunger in the H. pylori-negative FD patients. CONCLUSION: The preproghrelin 3056TT genotype is significantly associated with the acylated ghrelin levels and the feeling of hunger in H. pylori-negative FD patients. Further studies are needed to clarify the association between the preproghrelin 3056TT genotype and lower plasma acylated ghrelin levels and the impact of this relationship on the feeling of hunger in H. pylori-negative FD patients.

Sleep disorders in functional dyspepsia and future therapy.

Sleep disorder is a common medical problem. Sleep disorder has been associated with several diseases, including pulmonary disease, gastroesophageal reflux disease (GERD) and fibromyalgia. Interest in sleep phenomenology and gastrointestinal functioning has recently increased, because sleep disorder causes significant morbidity, as evidenced by the increased need for general medical and mental health treatment for emotional problems. A number of studies have found an association between sleep disorders and functional gastrointestinal (GI) disorders. Although arousal from sleep serves several protective roles, such as increase in the speed of esophageal clearance and in airway refluxes to prevent aspiration, awakening from sleep unfortunately induces impairment of sleep quality. Some investigations about the relationship between psychogenic factors and gut motility are controversial. In addition, reports of alterations in gut motility during sleep have also been contradictory. We have evaluated sleep disorder in functional dyspepsia (FD) patients using Pittsburgh Sleep Quality Index (PSQI) score. In our recent data, PSQI score of FD patients was significantly higher compared to that in healthy volunteers. Another study has reported that the distribution of subjects who thought that they got enough sleep was significantly lower for the FD/irritable bowel syndrome (IBS) subjects than for control subjects. Several studies have reported that anti-acid therapy and prokinetic agents are effective for certain FD patients. In addition, previous study has reported tricyclic antidepressants (TCA) drugs are effective for some FD patients. Finally, new drug, actiamide, a muscarinic antagonist and cholinesterase inhibitor, significantly improves Postprandial Distress Syndrome (PDS) symptoms. It might be critical issues for determination of precise mechanism for functional gastrointestinal disorders to clarify the relationship between gut motility and sleep disorders.