Usefulness of Practitioner-Led Pancreatic Cancer Screening.

The 5-year survival rate for pancreatic cancer has improved (10%) but remains worse than that for other cancers. Early pancreatic cancer diagnosis is challenging, and delayed diagnosis can delay treatment, which impairs survival. Practitioners do not promptly refer cases to a general hospital, causing delayed discovery. Herein, we aimed to examine the usefulness of the Pancreatic Cancer Project in Matsue, whose objective is to detect pancreatic cancer in patients presenting at any medical institution in Matsue City. Clinical data were extracted from medical records, and abdominal ultrasonography and tumor marker blood level assessments were performed (n = 234; median age, 71 [range, 41-94] years; 51% male). Cases with abnormal abdominal ultrasonography or blood test findings were referred for specialist imaging and followed up. The pancreatic cancer detection rate was 6.0% (n = 14); all cases were referred to a general hospital by practitioners within 1 month. Patients had stage IA (n = 1), IIA (n = 6), IIB (n = 2), III (n = 1), and IV (n = 4) disease. Overall, pancreatic cancer could be detected at an earlier stage (I-II), but referral to a general hospital by visiting practitioners should be prompt. The Pancreatic Cancer Project in Matsue may help improve the detection and prognosis of pancreatic cancer.

Specific locations of linear furrows in patients with esophageal eosinophilia.

BACKGROUND AND AIM: Linear furrows are the most frequently found endoscopic abnormality in patients with esophageal eosinophilia (EE); however, the precise endoscopic features remain to be fully elucidated. Here, we aimed to clarify the endoscopic features of EE, essential for the diagnosis of eosinophilic esophagitis (EoE), by focusing on the specific locations of linear furrows in a Japanese population. METHODS: We enrolled 70 cases with EE (≥15 eosinophils/high-power field) who were diagnosed at our hospital and related facilities. Information regarding endoscopic findings and clinical parameters was retrospectively reviewed. Next, the position of linear furrows in relation to esophageal longitudinal folds (ridge or valley) was evaluated in each case and compared with the position of mucosal breaks in patients with reflux esophagitis. Finally, the relationship between linear furrows and eosinophilic infiltration was evaluated. RESULTS: Of the 70 EE patients, 63 (90%) had linear furrows. Those occurred in a radial pattern and were widespread throughout the lower to upper esophagus, and exclusively found in esophageal longitudinal mucosal fold valleys, not on ridges, which was different from the position of mucosal breaks in patients with reflux esophagitis. Increased eosinophilic infiltration was significantly more frequent in linear furrows in the valleys (93%) as compared to mucosa on adjacent ridges (60%) (P < 0.05). CONCLUSION: Investigation of these endoscopic characteristics, especially by focusing on linear furrows in esophageal mucosal fold valleys, may provide important clues for more accurate diagnosis of EoE.

A report of three cases of exophytic gastrointestinal stromal tumor detected by transabdominal ultrasound.

Gastrointestinal stromal tumors (GISTs) are the most common submucosal tumors of the stomach. GISTs are often detected by esophagogastroduodenal endoscopy (EGD). However, the exophytic GIST type is relatively rare and difficult to detect by EGD. Most exophytic GISTs found are large and symptomatic. We present three cases with exophytic GISTs less than 5 cm in diameter detected by transabdominal ultrasound (TUS). All patients were asymptomatic and TUS revealed hypoechoic solid masses 2-3 cm in diameter between the stomach and left lobe of the liver. In contrast, no tumor in the stomach was detected by esophagogastroduodenal endoscopy. Endoscopic ultrasound and enhanced CT showed gastric tumors protruding outward. All three cases underwent partial gastrectomy, and the excised tumor was diagnosed as low-grade GIST. In conclusion, TUS can be a starting point for diagnosing exophytic GISTs of the stomach.

Therapeutic efficacy of pH-dependent release formulation of mesalazine on active ulcerative colitis resistant to time-dependent release formulation: analysis of fecal calprotectin concentration.

PURPOSE: Few reports have compared the clinical efficacy of a pH-dependent release formulation of mesalazine (pH-5-ASA) with a time-dependent release formulation (time-5-ASA). We examined whether pH-5-ASA is effective for active ulcerative colitis (UC) in patients resistant to time-5-ASA. METHODS: We retrospectively and prospectively analyzed the efficacy of pH-5-ASA in mildly to moderately active UC patients in whom time-5-ASA did not successfully induce or maintain remission. The clinical efficacy of pH-5-ASA was assessed by clinical activity index (CAI) before and after switching from time-5-ASA. In addition, the efficacy of pH-5-ASA on mucosal healing (MH) was evaluated in a prospective manner by measuring fecal calprotectin concentration. RESULTS: Thirty patients were analyzed in a retrospective manner. CAI was significantly reduced at both 4 and 8 weeks after switching to pH-5-ASA. In the prospective study (n=14), administration of pH-5-ASA also significantly reduced CAI scores at 4 and 8 weeks in these patients who were resistant to time-5-ASA. In addition, fecal calprotectin concentration was significantly decreased along with improvement in CAI after switching to pH-5-ASA. CONCLUSIONS: Our results suggest that pH-5-ASA has clinical efficacy for mildly to moderately active patients with UC in whom time-5-ASA did not successfully induce or maintain remission.

Reliability of symptoms and endoscopic findings for diagnosis of esophageal eosinophilia in a Japanese population.

BACKGROUND/AIMS: The clinical characteristics of esophageal eosinophilia (EE), which is essential for diagnosis of eosinophilic esophagitis (EoE), have not been fully clarified in a Japanese population. The aim of this study was to analyze the reliability of symptoms and endoscopic findings for diagnosing EE in Japanese individuals. METHODS: We prospectively enrolled subjects who complained of esophageal symptoms suggesting EoE and/or those with endoscopic findings of suspected EoE at the outpatient clinics of 12 hospitals. Diagnostic utility was compared between the EE and non-EE groups using logistic regression analysis. RESULTS: A total of 349 patients, including 319 with symptoms and 30 with no symptoms but endoscopic findings suggesting EoE were enrolled. Of those with symptoms, 8 (2.5%) had EE, and 3 were finally diagnosed with EoE. Of those without symptoms but endoscopic findings, 4 had EE. Among 8 symptomatic patients, 7 had abnormal endoscopic findings suspicious of EoE. Although dysphagia was a major symptom in EE, none of the presenting symptoms was useful for diagnosis of EE. Among the endoscopic findings, linear furrow was the most reliable (OR = 41.583). CONCLUSION: EE is uncommon among patients with esophageal symptoms in Japanese individuals. The most useful endoscopic finding for diagnosis of EE was linear furrow, whereas subjective symptoms were not supportive.

Effects of Rikkunshito (TJ-43) on Esophageal Motor Function and Gastroesophageal Reflux.

BACKGROUND/AIMS: Rikkunshito (TJ-43), an herbal medicine, has been demonstrated to relieve gastroesophageal reflux symptoms. However, the effects of TJ-43 on esophageal motor functions have not been fully determined. This double-blind crossover study was performed to investigate the effects of TJ-43 on esophageal motor functions and gastroesophageal reflux. METHODS: The subjects were 10 normal male volunteers. Lower esophageal sphincter pressure and esophageal body peristaltic contractions with and without 1-week administration of TJ-43 were examined in a crossover fashion. Post-prandial gastroesophageal reflux was also determined using a multi-channel impedance pH dual monitor. RESULTS: TJ-43 at a standard dose of 7.5 g/day did not significantly augment esophageal peristaltic contraction pressure measured in the proximal, middle and distal segments of the esophagus, whereas increment of resting lower esophageal sphincter pressure was observed in a supine position. In addition, TJ-43 administration did not decrease post-prandial gastroesophageal acid, non-acid reflux events or accelerate esophageal clearance time. CONCLUSIONS: TJ-43 at a standard dose did not have a significant effect on esophageal motor activity or gastroesophageal reflux in healthy adults.

[A case of hepatic angiosarcoma detected as a small lesion].

A 72-year-old man visited for imaging examination of alcoholic cirrhosis in April 2007. Enhanced CT images were revealed a 7 mm early enhanced lesion in segment 6 of the liver. The lesion was increased gradually to 40 mm on MRI images 21 months later. We performed ultrasound liver biopsy 3 times. Histology showed angiosarcoma with high-grade atypia and it was positive for CD31, CD34 and factor VIII-related antigen. The doubling time of this tumor was 42-108 days. Although we performed transarterial chemoembolization and interleukin-2 therapy, the patient died 34 months after the initial detection of tumor. We observed the clinical course with periodic imaging examination from the early stage of hepatic angiosarcoma and obtained a pathologic diagnosis by liver biopsy.

Usefulness of catheterless radiotelemetry pH monitoring system to examine the relationship between duodenal acidity and upper gastrointestinal symptoms.

BACKGROUND AND AIM: To clarify the usefulness of a newly designed method for measuring intraduodenal pH to examine the relationship between duodenal acidity and upper gastrointestinal symptoms during intragastric acid infusion. METHODS: The study subjects were six healthy volunteers. A Bravo pH capsule with thread fixed to the gastric wall was endoscopically introduced into the second portion of the duodenum, and intraduodenal acidity was measured during intragastric infusion of 300 mL of 0.1 mol/L hydrochloric acid or pure water through an elemental diet tube. The severity of several upper gastrointestinal symptoms were assessed by using a 10-cm visual analogue scale every 2 min for up to 30 min, and the area under the severity scale-time curve (cm×min.) were calculated. RESULTS: The percentage time during 30 min when the intraduodenal pH was <4.0 and was significantly greater than during water infusion (61.4±6.1% vs 24.8±6.5%). Several upper gastrointestinal symptoms were observed during acid infusion (acid vs water epigastric heaviness, 29.1±12.0 vs 2.7±1.4; dull epigastric pain, 8.8±4.9 vs 0.7±0.7 cm×min/30 min). Intraduodenal pH below 4.0 was correlated with the severity of dull pain in the stomach (R(2)=0.342, P=0.044). CONCLUSION: The newly designed intraduodenal pH monitoring by using catheterless radiotelemetry system is useful to examine the relationship between duodenal acidity and upper gastrointestinal symptoms.

Effects of mosapride on esophageal functions and gastroesophageal reflux.

BACKGROUND AND AIM: A substantial number of patients with gastroesophageal reflux disease show symptomatic resistance to high-dose proton pump inhibitors. In those cases, prokinetics are possible candidates for treatment. The aim of the present study was to determine whether mosapride, a prokinetic agent, stimulates esophageal functions, and prevents acidic and non-acidic gastroesophageal reflux. METHODS: Normal volunteers (nine and 13 for two experiments, respectively) were enrolled. Salivary secretion, esophageal peristaltic contractions, and resting lower esophageal sphincter pressure with and without mosapride administration were recorded using a cross-over protocol. Post-prandial acidic and non-acidic reflux levels were also recorded. RESULTS: Mosapride at a standard dose of 15 mg/day did not stimulate salivary secretion or any esophageal motor functions. It also failed to prevent acidic and non-acidic post-prandial gastroesophageal reflux. CONCLUSIONS: Mosapride at 15 mg/day, a standard dose in Japan, did not change the esophageal motility and salivary secretion in healthy volunteers. Future study on a larger number of individuals with higher dose of mosapride is worthwhile.

Effects of anti-hypertensive drugs on esophageal body contraction.

AIM: To clarify the effects of anti-hypertensive drugs on esophageal contraction and determine their possible relationship with gastro-esophageal reflux disease. METHODS: Thirteen healthy male volunteers were enrolled. Esophageal body peristaltic contractions and lower esophageal sphincter (LES) pressure were measured using high resolution manometry. All subjects were randomly examined on four separate occasions following administrations of nifedipine, losartan, and atenolol, as well as without any drug administration. RESULTS: Peristaltic contractions by the esophageal body were separated into three segments by two troughs. The peak peristaltic pressures in the mid and lower segments of the esophageal body under atenolol administration were significantly higher than those without medication in a supine position. On the other hand, peristaltic pressures under nifedipine administration were lower than those observed without drug administration. Losartan did not change esophageal body peristalsis. Atenolol elevated LES pressure and slowed peristaltic wave transition, while the effects of nifedipine were the opposite. CONCLUSION: Among the anti-hypertensive drugs tested, atenolol enhanced esophageal motor activity, which was in contrast to nifedipine.

Half-solidification of nutrient does not decrease gastro-esophageal reflux events in patients fed via percutaneous endoscopic gastrostomy.

BACKGROUND & AIMS: Percutaneous endoscopic gastrostomy (PEG) tube feeding is widely used for patients with swallowing dysfunction, and aspiration pneumonitis induced by reflux of gastric contents is one of the most frequent and life-threatening events in such patients. We performed this study to clarify the effect of half-solidification of nutrient on gastro-esophageal reflux (GER) of acidic and non-acidic gastric contents in patients with PEG. METHODS: The subjects were 14 elderly patients undergoing PEG feeding (female: 11, mean age 83.1 y). Twenty-four hour esophageal multichannel intraluminal impedance (MII) and pH (MII-pH) monitoring were performed during and after feeding with half-solid and liquid nutrient, respectively. The numbers of GER events during 4h after the start of feeding were compared. RESULTS: There was no significant difference in the total number of GER events between half-solid nutrient feeding and liquid nutrient feeding (5.6+/-1.5 vs. 6.6+/-1.5). The number of acid reflux events after half-solid nutrient feeding tended to be higher than that after liquid nutrient feeding (1.9+/-1.1 vs. 1.4+/-0.8). CONCLUSION: Half-solidification of nutrition does not appear to be effective for preventing GER caused by liquid PEG feeding.

Esophageal epithelial surface in patients with gastroesophageal reflux disease: an electron microscopic study.

AIM: To investigate the intercellular spaces between the most superficially located esophageal epithelial cells in patients with gastroesophageal reflux disease (GERD). METHODS: Eighteen patients with erosive esophagitis, 10 patients with non-erosive reflux disease (NERD), and 18 normal asymptomatic volunteers were enrolled. Biopsy specimens were obtained from the lower esophageal mucosa without ulcer or erosion. Scanning electron microscopy was employed to investigate the tightness of the superficial cellular attachment. RESULTS: The intercellular space between the most superficially located epithelial cells in patients with erosive esophagitis or NERD was not different from that in asymptomatic healthy individuals. CONCLUSION: Widened luminal intercellular spaces of esophageal superficial epithelium are not responsible for the induction of reflux symptoms in patients with GERD.

Helicobacter pylori infection does not accelerate the age-related progression of arteriosclerosis: a 4-year follow-up study.

BACKGROUND AND AIM: Helicobacter pylori (H. pylori) infection has been reported to correlate with the onset of cardiovascular diseases. However, the relationship between H. pylori infection and the progression of arteriosclerosis has not been fully investigated. The aim of this study was to clarify the possible role of H. pylori infection in the development of arteriosclerosis. METHODS: Study subjects were 258 cases who attended their annual medical check-ups and were twice investigated by the parameters of arteriosclerosis at a 4-year interval. Arteriosclerotic parameters (systolic blood pressure [SBP]), ankle brachial index [ABI], and pulse wave velocity [PWV]) were measured non-invasively using an automatic device. H. pylori-infection status was determined by assaying serum anti-H. pylori IgG antibodies. The changes in the arteriosclerotic parameters during the 4 years were compared between H. pylori-seropositive and seronegative individuals. RESULTS: A total of 166 subjects (64.3%) were H. pylori-seropositive. After adjustment for gender, age, body mass index, and smoking and drinking habits, there were no differences in any of the arteriosclerotic parameters between the groups, not only at enrollment but after the 4 years, although the high-density lipoprotein cholesterol levels of the seropositive groups were significantly lower than those of seronegative groups. SBP and PWVs were significantly increased during 4 years in both the seropositive and seronegative groups. The percentage of changes in SBP and PWVs, which were calculated by ([values after 4 years--values at enrollment/values at enrollment] x 100), did not differ between the groups. CONCLUSION: H. pylori infection does not accelerate the age-related progression of arteriosclerosis in Japanese individuals.

[Prevalence of gastro-esophageal reflux disease in patients who attended the emergency room].

BACKGROUND AND AIMS: Gastroesophageal reflux disease (GERD) is a well-known important cause of non-cardiac chest pain (NCCP). It has been shown that in western countries this condition can be in 22-66% of the cases. However, this situation is unclear in Japanese hospitals. We performed this study to clarify the frequency of GERD in NCCP patients who attended the emergency room. METHODS: We investigated the final diagnosis of the patients with chest pain who attended the emergency room of our hospital in March, June, September and December of 2005. RESULTS: Forty patients with NCCP attended the emergency room in the study periods. In these patients, only one patient (2.5%) was diagnosed as GERD. CONCLUSIONS: The results of this study showed that the frequency of GERD in NCCP patients of emergency room of Japan is lower than that of western countries.

[QOL of Japanese patients with GERD].

Gastroesophageal reflux disease(GERD) has been reported to be a pathological condition that decreases quality of life(QOL) of patients because of the various troublesome symptoms. To measure QOL, generic and disease specific instruments have been used in western countries. In Japan, some of these instruments are translated into the Japanese and are used for the measurement of QOL of various diseases. QOL of the Japanese patients with GERD are measured with the Japanese version of SF-36 and GSRS. As reported in western countries, QOL of the Japan patients with GERD are reported to be significantly decreased in comparison with those of healthy individuals.

Comments from the Developmental Neurotoxicology Committee of the Japanese Teratology Society on the OECD Guideline for the Testing of Chemicals, Proposal for a New Guideline 426, Developmental Neurotoxicity Study, Draft Document (October 2006 version), and on the Draft Document of the Retrospective Performance Assessment of the Draft Test Guideline 426 on Developmental Neurotoxicity.

In October 2006, a new revision of the draft guideline (OECD Guideline for the Testing of Chemicals, Proposal for a New Guideline 426. Developmental Neurotoxicity Study) and Draft Document of the Retrospective Performance Assessment (RPA) of the Draft Test Guideline 426 on Developmental Neurotoxicity were distributed following incorporation of the results of the Expert Consultation Meeting in Tokyo on May 24-26, 2005. The draft guideline consists of 50 paragraphs and an appendix with 102 references; and the draft RPA consists of 37 paragraphs with 109 references. National coordinators were requested to arrange for national expert reviews of these draft documents in their member countries. Members of the Developmental Neurotoxicology (DNT) Committee of the Japanese Teratology Society (JTS) reviewed, discussed, and commented on the draft Test Guideline Proposal. The DNT Committee of the JTS also commented on the draft document of the RPA. These comments were sent to the OECD Secretariat. The DNT Committee of the JTS expects the comments to be useful for the finalization of these draft documents.

Comments from the Behavioral Teratology Committee of the Japanese Teratology Society on OECD guideline for the testing of chemicals, proposal for a new guideline 426, developmental neurotoxicity study, draft document (September 2003).

In September 2003, a new revision of the draft guideline (Organization for Economic Co-operation and Development [OECD] Guideline for the Testing of Chemicals, Proposal for a New Guideline 426, Developmental Neurotoxicity Study) was distributed. The draft guideline consists of 51 paragraphs and an appendix. The National Coordinators were requested to arrange national expert reviews of the guideline proposal in their member countries. The member of the Behavioral Teratology (BT) Committee of the Japanese Teratology Society (JTS) reviewed, discussed and commented on the draft Test Guideline proposal. The BT Committee of the JTS also commented that the International Collaborative Study to validate this protocol should be definitely performed. These comments were sent to the OECD Secretariat. The BT Committee of the JTS expects that the comments are useful for further discussion.

Sequential morphological changes of erythrocyte apoptosis in Xenopus larvae exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

We previously demonstrated that 2,3,7,8-tetrachlorodibenzo-p-dioxin treatment of Xenopus laevis during the early stages of life induces apoptosis in larval erythrocytes (Sakamoto et al., 1997). In the present study, an examination of these cells at the ultrastructural level was undertaken to elucidate the sequential morphological changes that occur during apoptosis. Xenopus embryos were exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin for 5 days shortly after fertilization. The circulating erythrocytes in larvae 12 days after fertilization were examined. Ultramicroscopic studies revealed four roughly defined stages of apoptosis. During the first stage, many small roundish vacuoles begin to appear in the cytoplasm. No noticeable changes can be found in the nucleus. In the second stage, the perinuclear cisterna become dilated, and huge cisternae can be seen in some erythrocytes. The roundish cytoplasmic vacuoles also become larger. Condensation of nuclear chromatin is not yet evident and the erythrocytes still maintain their elliptical shape. During the third stage, chromatin condensation and margination along the nuclear membrane becomes apparent. The nuclear pores gather in the diffuse chromatin region where the perinuclear cisterna is not dilated. The cytoplasm of some erythrocytes also becomes condensed and electron-dense. The normal arrangement of microtubules is disorderly and the erythrocytes deform into a roundish shape. Also, macrophages usually contact some part of the cell. In the final stage, those erythrocytes which show typical nuclear condensation, where neither nuclear or cytoplasmic fragmentation have occurred, are almost or completely phagocytosed by macrophages.

Localization of Erythropoietin and Erythropoietin-Receptor in Postimplantation Mouse Embryos: (erythropoietin/erythropoietin receptor/universal morphogen/neurogenesis/mouse embryo).

We used RT-PCR (reverse transcription-polymerase chain reaction) and immunocytochemical methods to demonstrate the presence of erythropoietin (Ep) and its receptor (EpR) in postimplantation mouse embryos from the egg-cylinder to the unturned stage. Expression of mRNA for EpR was detected in total RNA from embryos and decidua in all these stages, but Ep mRNA was confined to embryos in the primitive streak stage and beyond and was not detected in the decidua. Staining of Ep and EpR was seen in all tissues, embryo proper and extra-embryonic. Moreover, regions of marked staining of Ep and EpR were detected in the extra-embryonic endoderm, embryonic ectoderm, neural folds and yolk sac, chronologically. No conspicuous differences were present in the staining patterns between Ep and EpR until primitive streak stage; however, after this stage, Ep was predominantly present in the nucleus and EpR on the surface of almost all cells; in the visceral yolk sac endoderm EpR was also detected in adsorption vacuoles and lipid droplets. These studies suggest that Ep first of exogenous and then endogenous origin and EpR of endogenous origin are involved not only in embryogenesis but also in neurogenesis and hematopoiesis in early postimplantation mouse embryos.