Ghrelin and gastric acid secretion

Ghrelin, a novel growth hormone-releasing peptide, was originally isolated from rat and human stomach. Ghrelin has been known to increase the secretion of growth hormone (GH), food intake, and body weight gain when administered peripherally or centrally. Ghrelin is also known to stimulate the gastric motility and the secretion of gastric acid. In the previous studies, the action of ghrelin on acid secretion was shown to be as strong as that of histamine and gastrin in in-vivo experiment. In the studies, the mechanism for the action of ghrelin was also investigated. It was shown that vagotomy completely inhibited the action of ghrelin on the secretion of gastric acid suggesting that vagal nerve is involved in the mechanism for the action of ghrelin on acid secretion. As famotidine did not inhibit ghrelin-in-duced acid secretion in the study by Masuda et al, they concluded that histamine was not involved in the action of ghrelin on acid secretion. However, we have shown that famotidine completely inhibited ghrelin-induced acid secretion and histidine decarboxylase (HDC) mRNA was increased in gastric mucosa by ghrelin injection which is inhibited by vagotomy Our results indicate that histamine is involved in the action of ghrelin on acid secretion. Furthermore synergistic action of gastrin and ghrelin on gastric acid secretion was shown. Although gastrin has important roles in postprandial secretion of gastric acid, ghrelin may be related to acid secretion during fasting period or at night. However, further studies are needed to elucidate the physiological role of ghrelin in acid secretion.

Comparison of endoscopic stenting for malignant biliary obstruction: A single-center study

AIM: To evaluate the efficacy and safety of single-step endoscopic placement of self-expandable metallic stents(SEMS) for treatment of obstructive jaundice.METHODS: A retrospective study was performed among 90 patients who underwent transpapillary biliary metallic stent placement for malignant biliary obstruction(MBO) between April 2005 and October 2012. The diagnosis of primary disease and MBO was based on abdominal ultrasound, computed tomography, magnetic resonance imaging, endoscopic ultrasound, endoscopic retrograde cholangiopancreatography with brush cytology, biopsy, and/or a combination of these modalities. The type of SEMS(covered or non-covered, 8 mm or 10 mm in diameter) was determined by the endoscopist. Ninety patients were divided into two groups: group 1(49 patients) who underwent a singlestep SEMS placement and group 2(41 patients) who underwent a two-step SEMS placement. The technical success rate, complication rate, stent patency, and patient survival rate were compared between the groups. In addition, to identify the clinical prognostic factors associated with patient survival, the following variables were evaluated in Cox-regression analysis: gender, age, etiology of MBO(pancreatic cancer or nonpancreatic cancer), clinical stage(Ⅳb; with distant metastases or Ⅳa >; without distant metastases), chemotherapy(with or without), patency of the stent, and the use of single-step or two-step SEMS. RESULTS: Immediate technical success was achieved in 93.9%(46/49) in group 1 and in 95.1%(39/41) in group 2, with no significant difference(P = 1.0). Similarly, there was no difference in the complication rates between the groups(group 1, 4.1% and group 2, 4.9%; P = 0.62). Stent failure was observed in 10 cases in group 1(20.4%) and in 16 cases in group 2(39.0%). The patency of stent and patient survival revealed no difference between the two groups with Kaplan-Meier analysis, with a mean patency of 111 ± 17 d in group 1 and 137 ± 19 d in group 2(P = 0.91), and a mean survival of 178 ± 35 d in group 1 and 222 ± 23 d in group 2(P = 0.57). On the contrary, the number of days of hospitalization associated with first-time SEMS placement in group 1 was shorter when compared with that number in group 2(28 vs 39 d; P < 0.05). Multivariate analysis revealed that a clinical stage of Ⅳa >(P = 0.0055), chemotherapy(P = 0.0048), and no patency of the stent(P = 0.011) were independent prognostic factors associated with patient survival.CONCLUSION: Our results showed that single-step endoscopic metal stent placement was safe and effective for treating obstructive jaundice secondary to various inoperable malignancies.

Is hepatic arterial infusion chemotherapy effective treatment for advanced hepatocellular carcinoma resistant to transarterial chemoembolization?

AIM:To evaluate the effectiveness of hepatic arterial infusion chemotherapy(HAIC) for advanced hepatocellular carcinoma(HCC) resistant to transarterial chemoembolization(TACE).METHODS:This study was conducted on 42 patients who received HAIC for advanced HCC between 2001and 2010 at our hospital.5-fluorouracil(5-FU) was administered continuously for 24 h from day 1 to day 5 every 2-4 wk via an injection reservoir.Intra-arterial cisplatin or subcutaneous interferon was administered in combination with the 5-FU.The patients enrolled in this retrospective study were divided into two groups according to whether or not they fulfilled the criteria for resistance to TACE proposed by the Japan Society of Hepatology in 2010(written in Japanese);one group of patients who did not fulfill the criteria for TACE resistance(group A,n = 23),and another group who fulfilled the criteria for TACE resistance(group B,n = 19).We compared the outcomes in terms of the response and survival rates between the two groups.RESULTS:Both the response rate and tumor suppression rate following HAIC were significantly superior in group A than in group B(response rate:48% vs 16%,P = 0.028,tumor suppression rate:87% vs 53%,P = 0.014).Furthermore,both the progression-free survival rate and survival time were significantly superior in group A than in group B(3-,6-,12-,and 24-mo = 83%,70%,29% and 20% vs 63%,42%,16% and 0%,respectively,P = 0.040,and 9.8 mo vs 6.2 mo,P = 0.040).A multivariate analysis(Cox proportional hazards regression model) showed that resistance to TACE was an independent predictor of poor survival(P = 0.007).CONCLUSION:HAIC administrating 5-FU was not effective against advanced HCC resistant to TACE.Other tools for treatment,i.e.,molecular-targeting agents may be considered for these cases.

Double balloon enteroscopy to retrieve an accidentally swallowed dental reamer deep in the jejunum

Accidentally swallowed foreign objects are not uncommon but difficult to manage without complications. We describe the case of a 68 year old man who accidentally a swallowed sharp-pointed dental reamer that had reached deep in his jejunum. Double balloon enteroscopic retrieval was performed with polypectomy snare but the reamer was entangled in the wire loop of the snare and penetrated the jejunal wall. After releasing the reamer by pushing and pulling the snare for approximately 30 min, the reamer was retrieved with biopsy forceps. This is the first report of double balloon enteroscopic removal of a dental reamer. Furthermore, this is a novel case with regard to decision making in situations when sharp objects are swallowed.

Erythropoietin -induced proliferation of gastric mucosal cells

AIM： To analyze the localization of erythropoietin receptor on gastric specimens and characterize the effects of erythropoietin on the normal gastric epithelial proliferation using a porcine gastric epithelial cell culture model. METHODS： Erythropoietin receptor was detected by RT-PCR, Western blotting and immunohistochermistry. Growth stimulation effects of erythropoietin on cultured gastric mucosal cells were determined by ELISA using bromodeoxyuridine （BrdU）. RESULTS： Erythropoietin receptor was detected on cultured porcine gastric mucosal epithelial cells. Erythropoietin receptor was also detected histochemically at the base of gastric mucosal epithelium. BrdU assay demonstrated a dose-dependent increase in growth potential of cultured porcine gastric mucosal epithelial cells by administration of erythropoietin, as well as these effects were inhibited by administration of antierythropoietin antibody （P〈 0.01）. CONCLUSION： These findings indicate that erythropoietin has a potential to proliferate gastric mucosal epithelium via erythropoietin receptor.

Jumbo biopsy is useful for the diagnosis of colonic prolapsing mucosal polyps with diverticulosis

We report here a case of multiple prolapsing mucosal polyps with diverticulosis in the sigmoid colon. A 52-year- old man was admitted to our hospital because of bloody diarrhea. Colonoscopy and barium enema showed multiple diverticula, markedly thickened mucosal folds and polypoid lesions with mucus on the top of them in the sigmoid colon. Endoscopic ultrasonography showed thickening of the mucosal and submucosal layers. Several endoscopic biopsy specimens were taken from the polypoid lesions. Histological examination revealed only chronic inflammatory cell infiltration. In order to obtain a definite diagnosis, we performed endoscopic jumbo biopsy for the polypoid lesions after obtaining informed consent. Histological examination revealed marked lymphocyte infiltration, hemosiderin deposits and fibromuscular obliteration in the lamina propria, features similar to those of mucosal prolapsing syndrome. After anti-diarrhetic treatment, clinical findings were improved. Thus, jumbo biopsy is useful for diagnosis and treatment of prolapsing mucosal polyps.

Experimental Evaluation of CT Number Changes in 320-Row CBCT Volume Scan for Proton Range Calculation

We investigated the longitudinal positional dependence of CT number in 320-row Cone Beam Computed Tomography (CBCT) volume scan (320-row volume scan) using a simple geometric phantom (SGP) and a chest simulation phantom (CSP) in order to evaluate its effect on proton range calculation. The SGP consisted of lung substitute material (LSM) and a cylindrical phantom (CP) made of high-density polyethylene. The CSP was an anthropomorphic phantom similar to the human chest. The two phantoms were scanned using 320-row volume scan in various longitudinal positions from the central beam axis. In experiments using the SGP, an image blur at the boundary of the two materials became gradually evident when the LSM was placed far away from the beam central axis. The image blur of the phantom was consistent with the gradation in CT number. The maximum difference in CT numbers between the 64-row helical scan and 320-row volume scan at the boundary of the two materials was consistent with approximately 50% of the relative proton stopping power. In contrast, the CT number profile in each longitudinal position was fairly consistent and longitudinal positional dependence rarely occurred in the CSP experiments. Pass lengths of CT beams through areas with widely different electron densities were shorter, and thus did not significantly impact CT numbers. Based on findings from the CSP experiments, we considered 320-row volume scan to be feasible for proton range calculation in clinical settings, although the relatively large longitudinal positional dependence of CT number should be accounted for when doing so.

Early effects of oral administration of omeprazole and roxatidine on intragastric pH

Objective： The ideal medication for the treatment of acid-related diseases, e.g., peptic ulcers, stress- related gastric bleeding, functional dyspepsia, and gastroesophageal reflux disease, should have a rapid onset of action to promote hemostasis and relieve the symptoms. The aim of our study was to investigate the inhibitory effects on gastric acid secretion of a single oral administration of a proton pump inhibitor, omeprazole 20 mg, and an H2-receptor antagonist, roxatidine 75 mg. Methods： Ten Heficobacterpylori-negative male subjects participated in this randomized, two-way crossover study. Intragastric pH was monitored continuously for 6 h after single oral admini- stration of omeprazole 20 mg and roxatidine 75 mg. Each administration was separated by a 7-d washout period. Results： During the 6-h study period, the average pH after administration of roxatidine was higher than that after administration of omeprazole （median： 4.45 vs. 2.65; P=0.0367）. Also during the 6-h study period, a longer duration of maintenance at pH above 2, 5, and 6 was observed after administration of roxatidine 75 mg than after administration of omeprazole 20 mg （median： 90.6% vs. 55.2%, P=-0.0284; 43.7% vs. 10.6%, P=0.0125; 40.3% vs. 3.3%, P=0.0125; respectively）. Conclusions： In Helicobacter pylori-negative healthy male subjects, oral administration of roxatidine 75 mg increased the intragastric pH more rapidly than that of omeprazole 20 mg.

Clinical efficacy of a combination of Percoll continuous density gradient and swim-up techniques for semen processing in HIV-1 serodiscordant couples

To evaluate the clinical efficacy of a procedure comprising a combination of Percoll continuous density gradient and modified swim-up techniques for the removal of human immunodeficiency virus type 1 （HIV-1） from the semen of HIV-1 infected males, a total of 129 couples with an HIV-1 positive male partner and an HIV-1 negative female partner （serodiscordant couples） who were treated at Keio University Hospital between January 2002 and April 2012 were examined. A total of 183 ejaculates from 129 HIV-1 infected males were processed. After swim-up, we successfully collected motile sperms at a recovery rate as high as 100.0% in cases of normozoospermia （126/126 ejaculates）, oligozoospermia （6/6）, and asthenozoospermia （36/36）. The recovery rate of oligoasthenozoospermia was 86.7% （13/15）. In processed semen only four ejaculates （4/181：2.2%） showed viral nucleotide sequences consistent with those in the blood of the infected males. After using these sperms, no horizontal infections of the female patients and no vertical infections of the newborns were observed. Furthermore, no obvious adverse effects were observed in the offspring. This protocol allowed us to collect HIV-1 negative motile sperms at a high rate, even in male factor cases. We concluded that our protocol is clinically effective both for decreasing HIV-1 infections and for yielding a healthy child.

Sodium-glucose cotransporter 2 inhibitors in Asian patients with heart failure

To the Editor:Sodium-glucose cotransporter 2(SGLT-2)inhibitors are recognized as one of the essential drugs for the treatment of heart failure(HF).Recent randomized controlled trials(RCTs)have shown that the SGLT-2 inhibitors significantly reduced the occurrence of HF hospitalizations or cardiovascular mortality in HF patients.