Relationship between nutritional therapy and surgery in Crohn's disease.

BACKGROUND/AIMS: Crohn's disease is often refractory and some patients require repeated surgical treatment. Nutritional therapy with an elemental diet has been reported effective in improving nutritional state and suppressing inflammation, and might be expected to assist in minimizing the need for surgery. We evaluated the relationship between an elemental diet and the period that patients spent without intestinal resection. METHODOLOGY: A total of 153 patients with Crohn's disease who visited our hospital from July, 1999 to July, 2005 were enrolled. The relationship between the caloric content of an elemental diet and surgery as an endpoint was examined using Cox regression analysis. Cumulative non-operation rates were calculated by the Kaplan-Meier method. Statistical significance was determined using the log-rank test. RESULTS: Among patients with jejunoileal involvement, patients receiving an elemental diet providing 900 kcal or more per day showed a statistically significant improvement in cumulative non-operation rate. Among those without jejunoileal involvement, in contrast, the cumulative non-operation rate did not differ among those receiving an elemental diet of less or more than 900 kcal per day. CONCLUSIONS: The use of an elemental diet of 900 kcal per day may be effective in avoiding surgery in patients with jejunoileal lesions. This diet may be useful in improving long-term convalescence in these patients.

Rebamipide enema therapy as a treatment for patients with active distal ulcerative colitis.

BACKGROUND: The clinical efficacy of corticosteroids in the treatment of ulcerative colitis (UC) is well-established. However, prolonged usage of these drugs can result in serious complications. Rebamipide {2-(4-chlorobenzoylamino)-3[2-(1H)-quinolinon-4-yl] propionic acid}, a cytoprotective agent, has been reported to have anti-inflammatory activity and to repair mucosal injury in animal colitis models. The aim of the present study was to assess the clinical efficacy and safety of a novel Rebamipide enema therapy in UC patients. METHODS: Twenty patients with the active distal type of UC in whom corticosteroid treatment had been unsuccessful were treated with rectal administration of Rebamipide twice a day for 3 weeks, during which corticosteroid dosage was kept constant. The efficacy of treatment was assessed from clinical symptoms and endoscopic findings. The anti-inflammatory effect of Rebamipide was also examined by monitoring changes in the intensity of histological inflammation and levels of cytokine activity in the rectal mucosa. RESULTS: At 3 weeks after the initiation of Rebamipide enema therapy, 11 patients (55%) achieved clinical remission. Sixteen (80%) were colonoscopically judged to be responders, with decreased levels of interleukin (IL)-1beta but not of IL-8, and an increased ratio of IL-1 receptor antagonist/IL-1beta in organ cultures of mucosal tissues. The change in the number of infiltrating neutrophils was not significantly correlated with the clinical response to this therapy. No side-effects were noted in any patients. CONCLUSION: Rebamipide enema therapy proved to be safe and useful in corticosteroid-refractory patients with the active distal type of UC.

Therapeutic efficacy of infliximab on active Crohn's disease under nutritional therapy.

OBJECTIVE: The aim of this investigation was to elucidate retrospectively the therapeutic effect of infliximab in patients with active Crohn's disease (CD) under nutritional therapy. MATERIAL AND METHODS: Using a review of the clinical records in 24 nationwide institutions specializing in inflammatory bowel disease, the short-term effect of infliximab in 97 patients with active CD was retrospectively investigated. The Crohn's disease activity index (CDAI) at baseline and after 2 weeks of a single infliximab administration (5 mg/kg) was compared among patients under total parenteral nutrition (TPN group, n=36), those following an elemental or polymeric diet (EN group, n=49) and those without TPN and EN (NN group, n=12). A decrease in CDAI >or= 70 or a CDAI value <150 at 2 weeks was regarded as effective. RESULTS: There was no difference in CDAI at baseline among the three groups. In each group, CDAI decreased significantly (from 250 (195-290) [median (interquartiles)] to 152 (123-233) in the TPN group, p<0.0001; from 259 (200-325) to 180 (130-238) in the EN group, p<0.0001; from 278 (222-291) to 164 (132-196) in the NN group, p=0.003). Infliximab was effective in 63.9% of patients in the TPN group, in 55.1% of those in the EN group and in 75% of the NN group. There was no statistical difference in efficacy among the three groups (p=0.4). Multivariate logistic regression analysis revealed younger age to be a significant factor related to the efficacy of infliximab. CONCLUSIONS: Infliximab is effective in patients with CD under TPN or EN. Age at infliximab administration may be predictive of response to infliximab.

Long-term follow-up after eradication of Helicobacter pylori with omeprazole, clarithromycin, and tinidazole (OCT regimen) in a Japanese population.

BACKGROUND: The long-term benefit of Helicobacter pylori eradication treatment that includes metronidazole on peptic ulcer disease in Japan is unclear. We investigated the rate of H. pylori re-infection and ulcer relapse after H. pylori eradication. MATERIALS AND METHODS: A total of 266 patients with endoscopically confirmed peptic ulcer disease and H. pylori infection were treated with triple therapy of omeprazole 40 mg (20 mg b.i.d.), clarithromycin 800 mg (400 mg b.i.d.), and tinidazole 1000 mg (500 mg b.i.d.) for 7 days. Endoscopy with gastric biopsy was performed before and 1 month, 6 months, 1.5 years, and 3.5 years after therapy. H. pylori status was determined by H. pylori culture, rapid urease test, and histopathology. 13C-urea breath test was done at 6 months after eradication therapy. Treatment was deemed successful when all tests were negative at 6 months after therapy by endoscopic biopsy. RESULTS: Successful H. pylori eradication was achieved in 262/266 (98.5%) patients with peptic ulcer. Total relapse of peptic ulcer occurred in 8/262 (3%) patients after eradication, with 3/262 (1.1%) occurring within 1.5 years after treatment and 5/262 (1.9%) within 3.5 years. All relapsed patients were found to be H. pylori-positive at the time of relapse. Of the 262 patients who experienced eradication, 20 (7.6%) were subsequently re-infected, six (2.3%) within 1.5 years and 14 (5.3%) within 3.5 years. CONCLUSION: Triple therapy with omeprazole, clarithromycin, and tinidazole (OCT) is useful for H. pylori eradication in Japan, but there is an appreciable re-infection rate in this population.

Intestinal fibroblast-derived IL-10 increases survival of mucosal T cells by inhibiting growth factor deprivation- and Fas-mediated apoptosis.

Mucosal T cells are essential to immune tolerance in the intestine, an organ constantly exposed to large amounts of dietary and bacterial Ags. We investigated whether local fibroblasts affect mucosal T cell survival, which is critical for maintenance of immune tolerance. Coculture with autologous fibroblasts significantly increased viability of mucosal T cells by inhibiting IL-2 deprivation- and Fas-mediated apoptosis, an effect that was both contact- and secreted product-dependent. Investigation of anti-apoptotic factors in the fibroblast-conditioned medium (FCM) revealed the presence of IL-10 and PGE2, but not IFN-beta, IL-2, or IL-15. Although recombinant IFN-beta, but not PGE2, effectively prevented T cell apoptosis, neutralizing Ab studies showed that only IL-10 blockade significantly increased T cells apoptosis, whereas neutralizing IFN-beta or IFN-alpha failed to inhibit the anti-apoptotic effect of FCM. To confirm that fibroblast-derived IL-10 was responsible for preserving mucosal T cell viability, IL-10 mRNA was demonstrated in fibroblasts by Southern blotting and RT-PCR. When FCM was submitted to HPLC fractionation, only the peak matching rIL-10 contained the anti-apoptotic activity, and this was eliminated by treatment with an IL-10-neutralizing Ab. Finally, when fibroblasts were transiently transfected with IL-10 antisense oligonucleotides, the conditioned medium lost its T cell anti-apoptotic effect, whereas medium from fibroblasts transfected with IFN-beta antisense oligonucleotides displayed the same anti-apoptotic activity of medium from untransfected fibroblasts. These results indicate that local fibroblast-derived IL-10 is critically involved in the survival of mucosal T cells, underscoring the crucial importance of studying organ-specific cells and products to define the mechanisms of immune homeostasis in specialized tissue microenvironments like the intestinal mucosa.

Leukocytapheresis in ulcerative colitis: results of a multicenter double-blind prospective case-control study with sham apheresis as placebo treatment.

OBJECTIVE: Leukocytapheresis (LCAP) is a method of therapeutic apheresis that removes peripheral leukocytes. Previous studies showed that in patients with ulcerative colitis (UC), LCAP was more effective than high-dose steroid therapy, and it had few adverse effects. We investigated LCAP in a multicenter study using active and sham devices in a double-blind study in order to elucidate the placebo effect of extracorporeal treatment including anticoagulant medication. METHODS: Twenty-five patients with active UC of severe or moderately severe grade were enrolled and assigned to the active group or the sham group. Six patients were excluded from the study and 19 (10 in the active group and nine in the sham group) were evaluated. LCAP (treatment using an active device or a sham device) was performed once a week for 5 wk, followed by two additional sessions during the next 4 wk at 2-wk intervals. Steroids and other medications were continued at the same dosage for 4 wk, which included a 2-wk pre-observation period and the first 2 wk after the start of the LCAP treatment. New medications or increase in the dosage of previous medication were prohibited until evaluation was conducted. RESULTS: The clinical activity index (CAI) value of UC, indicated that the active group showed a significantly greater improvement (80%, 8/10) than the sham group (33%, 3/9; p<0.05). Adverse effects were observed in five patients (one in the active group and four in the sham group). None of these effects was severe and none of the sessions was terminated as a consequence of the adverse effects. CONCLUSION: The results confirmed that LCAP is a safe and effective therapeutic option for patients with active UC.

[Enema therapy for ulcerative colitis patients].

The therapeutic options for the treatment of mildly to moderately active distal colitis or distal flare up of total colitis have increased over the last decade. Many reports have documented the effectiveness of various compounds, such as 5-aminosalicylic acid, steroids, cytoprotective agents, lidocaine gel, short chain fatty acid, and cyclosporine when they are applied topically to the inflamed distal colon in patients with ulcerative colitis. These treatments have considerably attracted our attention because of their possible anti-inflammatory effects on ulcerative colitis with lower toxicity. Larger, controlled studies will be necessary to establish the roles of enema therapy in patients with distal colitis.

Possible involvement of the interleukin-15 and interleukin-15 receptor system in a heightened state of lamina propria B cell activation and differentiation in patients with inflammatory bowel disease.

BACKGROUND: We investigated the possible roles of the interleukin (IL)-15 and IL-15 receptor (IL-15R) system in a heightened state of B-cell activation and differentiation in intestinal mucosa with inflammatory bowel disease (IBD). METHODS: The expression of IL-15 and IL-15Ralpha mRNA and protein in inflamed colonic mucosal tissues with IBD, and in control tissues was examined by reverse transcriptase-polymerase chain reaction and immunohistological methods. The effects of recombinant (r)IL-15 on the expression of IL-15Ralpha on lamina propria B cells and the production of immunoglobulin G (IgG) were analyzed in vitro, using lamina propria mononuclear cells (LPMCs) isolated from control tissues. RESULTS: The intensity of IL-15 and IL-15Ralpha mRNA was greater in the mucosal tissues of patients with IBD, especially in those of patients with ulcerative colitis (UC), than in control tissues. Compared to control tissues, mononuclear cells positive for IL-15Ralpha protein were observed in greater proportions in tissue sections from patients with IBD, especially in those from patients with UC, where IL-15Ralpha protein was localized to CD20-positive B cells to a significant degree. There were increases in the proportions of IL-15Ralpha-positive B cells and IgG-producing cells in rIL-15- or rCD40L-stimulated cultures of LPMCs, with stimulatory effects being greater in the presence of their combination. CONCLUSIONS: These data suggest that the IL-15 and IL-15R system may play important roles in the activation and differentiation of lamina propria B cells in patients with IBD, especially in those with UC.

Interleukin-17 levels in Helicobacter pylori-infected gastric mucosa and pathologic sequelae of colonization.

AIM: To determine the role of interleukin (IL)-17 in gastric ulcerogenesis. METHODS: Thirty-six gastric ulcer (GU) patients and 29 non-ulcer (NU) patients were enrolled in this study. Mucosal biopsy samples were obtained from the gastric antrum and GU site during endoscopy. Samples were used in in situ stimulation for 48 h in the presence of 10 microg/mL phytohemagglutinin-P (PHA), histological examination, and Helicobacter pylori (H pylori) culture. IL-17 and IL-8 protein levels in culture supernatants were assayed by ELISA. IL-17 mRNA expression was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR). H pylori cagA and vacA status was assessed by reverse hybridization using a line probe assay (LiPA). IL-8 levels in culture supernatants were assayed after AGS cells were co-cultured with H pylori strain 26,695 or recombinant human (rh) IL-17. RESULTS: All 36 GU patients and 15 of 29 NU patients were found to be H pylori-positive, while 14 NU patients were H pylori-negative. All 51 H pylori strains from both GU and NU patients were cagA- and vacAs1/m1-positive. Antral mucosal tissues from H pylori-positive patients contained significantly (H pylori-positive NU patients: median 467 pg/mg/protein, range 53-2,499; H pylori-negative NU patients: median 104 pg/mg/protein, range 16-312, P< 0.0005) higher levels of IL-17 than those from uninfected patients. IL-17 levels at the ulcer site were significantly (ulcer site: median 1,356 pg/mg/protein, range 121-1,3730; antrum: median 761 pg/mg/protein, range 24-7,620, P< 0.005) higher than those at distant sites in the antrum. Biopsies from H pylori-positive GU and NU patients showed IL-17 mRNA expression in all samples whereas those from the antrum of the H pylori-negative controls showed no detectable expression. A significant correlation was seen between IL-17 and IL-8 levels at each biopsy site (ulcer: r = 0.62, P< 0.0001; antrum: r = 0.61, P< 0.0001) in GU patients. RhIL-17 and H pylori strain 26,695 each stimulated IL-8 production from AGS cells. CONCLUSION: IL-17 may play an important role in the inflammatory response to H pylori colonization, and may ultimately influence the outcome of H pylori-associated diseases that arise within the context of gastritis.

Immunomodulatory therapy for inflammatory bowel disease.

Patients with inflammatory bowel disease (IBD) have intestinal and extraintestinal symptoms that can greatly impair their quality of life. They must rely on multiple medications with aminosalicylates, corticosteroids, and purine analogues to control these symptoms. Although decades of clinical experience in IBD management has led to optimized approaches for achieving the induction and maintenance of remission, the disease in some patients is still refractory to conventional medical treatment, or the effectiveness of these drugs can be limited by treatment-related side effects. Significant progress in our understanding of the pathogenesis of IBD has yielded several immunomodulatory approaches with novel biological agents or apparatus, such as cyclosporine, cytoprotective agents, infliximab, and leukocytapheresis. Further immunomodulatoy therapy, aiming at the inhibition of molecular and cellular mediators, is anticipated, in parallel with the clarification of im-munoinflammatory pathways in IBD. An additional goal will be to identify factors predictive of response to treatment with each novel immunomodulatory agent or apparatus. This will help provide each patient with optimized and individualized therapy, thereby increasing therapeutic efficacy and reducing possible side effects.

Characteristics of Helicobacter pylori-induced gastritis and the effect of H. pylori eradication in patients with chronic idiopathic thrombocytopenic purpura.

BACKGROUND: The association between Helicobacter pylori infection and idiopathic thrombocytopenic purpura (ITP) has been reported widely. We investigated the prevalence of H. pylori infection, its virulence profile and the effectiveness of its eradication in patients with ITP. MATERIALS AND METHODS: Twenty patients with ITP, 20 with peptic ulcer (10 gastric ulcer (GU), 10 duodenal ulcer (DU)) and 20 with NUD were studied. The virulence profile of the strains was assessed by genotyping for cagA, vacA, iceA, and hpyIIIR/hrgA and by assaying for IL-8 and DNA fragmentation after incubation with AGS cells. Infected patients and two uninfected ITP patients received triple therapy and platelets were counted before and 1 month, 6 months, 1 year, and 2 years after eradication therapy. RESULTS: H. pylori infection was found in 17 ITP (85%), 20 ulcer (100%) and 13 NUD (65%) patients. Biopsies and strains were collected from five ITP, 20 ulcer and 13 NUD patients. The ITP patients had a pangastritis or corpus-predominant gastritis pattern. All H. pylori isolates, from ITP, ulcer and NUD patients, were cagA(+) and vacA s1/m1, and did not differ in levels of IL-8 induction or DNA fragmentation. Fifteen ITP (88%) and 17 ulcer (85%) patients had successful eradication of H. pylori. Ten of these 15 (67%) H. pylori-eradicated ITP patients had platelet recovery. There was no significant change in platelet count in the two ITP patients in whom eradication failed or in the two originally H. pylori-uninfected ITP patients, or in the treated ulcer patients. Age at onset of ITP was the main determinant of platelet recovery: 100% of patients diagnosed after the age of 60 recovered compared with only 22% of those diagnosed before 50. CONCLUSIONS: H. pylori-infected ITP patients have a corpus-predominant pattern of gastritis but the virulence profile of their strains does not differ from that of ulcer or NUD patients. Eradication of H. pylori infection is a good therapeutic option for some patients with chronic ITP, especially for those who develop ITP in older age.

Effect of glycine on Helicobacter pylori in vitro.

Glycine is the simplest amino acid and is used as a metabolic product in some bacteria. However, an excess of glycine inhibits the growth of many bacteria, and it is used as a nonspecific antiseptic agent due to its low level of toxicity in animals. The effect of glycine on Helicobacter pylori is not precisely known. The present study was conducted to investigate (i) the effect of glycine on clarithromycin (CLR)-resistant and -susceptible strains of H. pylori, (ii) the effect of glycine in combination with amoxicillin (AMX), and (iii) the postantibiotic effect (PAE). The MIC at which 90% of strains are inhibited for glycine was almost 2.5 mg/ml for 31 strains of H. pylori, including CLR-resistant strains. We constructed isogenic CLR-resistant mutant strains by natural transformation and investigated the difference between clinical wild-type strains and isogenic mutants. There were no differences in the MICs between CLR-resistant and -susceptible strains or between clinical wild-type and mutant strains. The combination of AMX and glycine showed synergistic activity, with the minimum bactericidal concentration of AMX with glycine decreasing to 1/10 that of AMX alone. Glycine showed no PAE against H. pylori. These results suggest that glycine may be a useful antimicrobial agent against H. pylori not only alone but also in combination with antibacterial drugs for the treatment of H. pylori-associated diseases. Glycine may represent a component of a new type of eradication therapy for CLR-resistant H. pylori.

Recurrent peptic ulcers in patients following successful Helicobacter pylori eradication: a multicenter study of 4940 patients.

OBJECTIVE: Although curative treatment of Helicobacter pylori infection markedly reduces the relapse of peptic ulcers, the details of the ulcers that do recur is not well characterized. The aim of this study is to describe the recurrence rate and specific features of peptic ulcers after cure of H. pylori infection. METHODS: This was a multicenter study involving 4940 peptic ulcer patients who were H. pylori negative after successful eradication treatment and were followed for up to 48 months. The annual incidence of ulcer relapse in H. pylori-cured patients, background of patients with relapsed ulcers, time to relapse, ulcer size, and site of relapsed ulcers were investigated. RESULTS: Crude peptic ulcer recurrence rate was 3.02% (149/4940). The annual recurrence rates of gastric, duodenal and gastroduodenal ulcer were 2.3%, 1.6%, and 1.6%, respectively. Exclusion of patients who took NSAIDs led annual recurrence rates to 1.9%, 1.5% and 1.3%, respectively. The recurrence rate was significantly higher in gastric ulcer. Recurrence rates of patients who smoked, consumed alcohol, and used NSAIDs were significantly higher in those with gastric ulcer recurrence compared to duodenal ulcer recurrence (e.g. 125 of 149 [83.9%] relapsed ulcers recurred at the same or adjacent sites as the previous ulcers). CONCLUSIONS: Curative treatment of H. pylori infection is useful in preventing ulcer recurrence. Gastric ulcer is more likely to relapse than duodenal ulcer. Recurrent ulcer tended to recur at the site of the original ulcers.

A pilot randomized trial of a human anti-interleukin-6 receptor monoclonal antibody in active Crohn's disease.

BACKGROUND & AIMS: Interleukin-6 (IL-6) regulates immune response and inflammation. We carried out a pilot placebo-controlled study to investigate the efficacy, pharmacokinetics, and safety of MRA, a humanized monoclonal antibody to IL-6 receptor, in patients with active Crohn's disease. METHODS: Thirty-six patients with active Crohn's disease (Crohn's Disease Activity Index [CDAI] > or =150) were randomly assigned to receive biweekly intravenous infusion of either placebo, MRA, or MRA/placebo alternately for 12 weeks at a dose of 8 mg/kg. The study's primary end point was a clinical response rate that was defined as a reduction of CDAI > or =70. RESULTS: At the final evaluation, 80% of the patients (8 of 10) given biweekly MRA had a clinical response as compared with 31% of the placebo-treated patients (4 of 13; P = 0.019). Twenty percent of the patients (2 of 10) on this regimen went into remission (CDAI <150), as compared with 0% of the placebo-treated patients (0 of 13). The clinical response rate of the every-4-week regimen was 42% (5 of 12). The serum concentrations of MRA were detected at 2 weeks after every infusion, at which time acute phase responses were completely suppressed; however, they were not suppressed at 4 weeks. Endoscopic and histologic examination showed no difference between MRA and placebo groups. The incidence of adverse events was similar in all the groups. CONCLUSIONS: This is the first clinical trial of humanized anti-IL-6 receptor monoclonal antibody in Crohn's disease. A biweekly 8 mg/kg infusion of MRA was well tolerated, normalized the acute-phase responses, and suggests a clinical effect in active Crohn's disease.

Plakoglobin (gamma-catenin) has TCF/LEF family-dependent transcriptional activity in beta-catenin-deficient cell line.

Beta-catenin is an essential element for the transcriptional activation of target genes in the Wnt signaling cascade and is also a cell adhesion molecule that couples with cadherins. Although plakoglobin (gamma-catenin), a closely related homologue of beta-catenin, is also known to be a cell adhesion molecule, its function as a transcriptional factor has not been revealed in detail. Using a human malignant mesothelioma cell line, NCI-H28, in which we have identified a homozygous deletion of the beta-catenin gene, we studied whether plakoglobin has a T-cell factor/lymphocyte enhancer factor (TCF/LEF) family-dependent transcriptional activity. Transfection with the wild-type plakoglobin expression vector induced accumulation of plakoglobin in the nucleus. Immunoprecipitation assay with cotransfection of plakoglobin and either TCF-4 or LEF-1 detected binding of plakoglobin to TCF-4 or LEF-1. Luciferase reporter assay demonstrated transcriptional activity of the wild-type plakoglobin when transfected with TCF/LEF, although plakoglobin showed less activity than beta-catenin. Exogenous plakoglobin was also shown to promote entrance of exogenous beta-catenin into the nuclei. Furthermore, small interfering RNA directed against plakoglobin suppressed expression of endogenous plakoglobin and its transcriptional activity, suggesting that endogenous plakoglobin has a weak transcriptional activity. These results suggest that plakoglobin can activate the Wnt signaling cascade directly without interaction of beta-catenin, and that plakoglobin has multiple functions as a transcriptional activator and a cell adhesion molecule like beta-catenin.

Concurrent chemoradiotherapy for locally advanced and metastatic esophageal cancer: longterm results of a phase II study of UFT/CDDP with radiotherapy.

BACKGROUND: No effective treatment for advanced esophageal cancer extending to adjacent organs or associated with distant metastasis is known. We prospectively analyzed the efficacy of concurrent chemoradiotherapy with uracil plus tegafur (UFT) and cisplatin (CDDP) for such cases of advanced esophageal cancer. METHODS: Patients with advanced cancers received 60 to 70 Gy of radiotherapy given during a period of 7 weeks, concurrently with daily oral UFT (200 mg/m(2) per day), and a 24-h infusion of CDDP (70 mg/m(2)) on days 8 and 36. After chemoradiotherapy, UFT (250 mg/m(2)/per day) was administered daily for 1 year, while CDDP (80 mg/m(2)) was administered twice every 4 weeks. RESULTS: Patients with stage III disease numbered 31, while 24 had stage IV disease according to the tumor-node-metastasis (TNM) staging. Including all patients, complete response (CR) occurred in 20% and partial response (PR) in 51%. In stage III patients, CR, PR, and CR+PR rates were 29%, 48%, and 77%, respectively. In stage IV patients, CR, PR, and CR+PR rates were 8%, 54%, and 63%. Grade 4 leukocytopenia occurred in 22% of patients, and grade 3 pain, nausea/vomiting, and oral mucositis occurred in 7%, 9%, and 4% of patients respectively, but resolved after the reduction or discontinuation of chemoradiotherapy. Median survival in stage III patients was 415 days (range, 3 to 3046 days), and in stage IV patients, it was 187 days (range, 75 to 764 days). The 2-year survival rate in stage III patients was 25% and it was 4% in stage IV patients. The 5-year survival rate in stage III patients was 7%, while in stage IV patients it was 0%. CONCLUSION: This combined treatment may be a promising nonsurgical management option for locally advanced esophageal cancer, and can achieve good palliative effects in patients with distant metastasis.

Enhanced somatostatin secretion into the gastric juice with recovery of basal acid output after Helicobacter pylori eradication in gastric ulcers.

BACKGROUND AND AIM: Antral somatostatin interacts with gastric acid secretion. We aimed to investigate the effect of eradication on gastric acid, somatostatin secretion and mucosal histology in gastric ulcer patients with Helicobacter pylori (H. pylori) infection. METHODS: Twenty-eight patients (21 male, 7 female) with H. pylori-positive gastric ulcer were treated with dual therapy. Before and 4-8 weeks after the therapy, the histology of biopsy specimens, basal acid output (BAO) and maximal acid output (MAO) after stimulation with tetragastrin were assessed. Somatostatin concentration in the gastric juice was measured by radioimmunoassay, and somatostatin output during either the basal or gastrin-stimulated period was also examined. RESULTS: Eradication was successful in 22 patients. Before treatment, the acid and somatostatin output were inversely related to the severity of neutrophil infiltration in the corpus and antrum, respectively. After successful eradication, improvement of histological inflammation and an increase in BAO, basal and gastrin-stimulated somatostatin output were observed. Eradication had no effect on atrophy and MAO. There was a positive correlation between gastric acid and somatostatin output in the basal or stimulated condition, irrespective of H. pylori infection. CONCLUSIONS: The present results suggest that recovery of gastric BAO may be caused by an improvement in corpus neutrophil infiltration, but not by an increase in parietal cell volume or a change in atrophy. Also, there was an increase in basal and gastrin-stimulated somatostatin-containing cell activity accompanied by improved antral neutrophil infiltration in the early phase after H. pylori eradication in gastric ulcers.