Narrow-band imaging versus Lugol chromoendoscopy for esophageal squamous cell cancer screening in normal endoscopic practice: randomized controlled trial.

BACKGROUND: Narrow-band imaging (NBI) is as sensitive as Lugol chromoendoscopy to detect esophageal squamous cell carcinoma (SCC) but its specificity, which appears higher than that of Lugol chromoendoscopy in expert centers, remains to be established in general practice. This study aimed to prove the superiority of NBI specificity over Lugol chromoendoscopy in the detection of esophageal SCC and high grade dysplasia (HGD) in current general practice (including tertiary care centers, local hospitals, and private clinics). METHODS: This prospective randomized multicenter trial included consecutive patients with previous or current SCC of the upper aerodigestive tract who were scheduled for gastroscopy. Patients were randomly allocated to either the Lugol or NBI group. In the Lugol group, examination with white light and Lugol chromoendoscopy were successively performed. In the NBI group, NBI examination was performed after white-light endoscopy. We compared the diagnostic characteristics of NBI and Lugol chromoendoscopy in a per-patient analysis. RESULTS: 334 patients with history of SCC were included and analyzed (intention-to-treat) from 15 French institutions between March 2011 and December 2015. In per-patient analysis, sensitivity, specificity, positive and negative likelihood values were 100 %, 66.0 %, 21.2 %, and 100 %, respectively, for Lugol chromoendoscopy vs. 100 %, 79.9 %, 37.5 %, and 100 %, respectively, for NBI. Specificity was greater with NBI than with Lugol (P = 0.002). CONCLUSIONS: As previously demonstrated in expert centers, NBI was more specific than Lugol in current gastroenterology practice for the detection of early SCC, but combined approaches with both NBI and Lugol could improve the detection of squamous neoplasia.

Diagnostic value of CA19.9, circulating tumour DNA and circulating tumour cells in patients with solid pancreatic tumours.

BACKGROUND: The direct comparison of CA19.9, circulating tumour cells (CTCs) and circulating tumour DNA (ctDNA) using endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has never been performed for the diagnosis of solid pancreatic tumours (SPTs). METHODS: We included 68 patients with a SPT referred for EUS-FNA. CTCs were analysed using size-based platform and ctDNA using digital PCR. The sensitivity, specificity, negative and positive predictive values were evaluated for each marker and their combination. RESULTS: SPTs corresponded to 58 malignant tumours (52 pancreatic adenocarcinoma (PA) and 6 others) and 10 benign lesions. The sensitivity and specificity for PA diagnosis were 73% and 88% for EUS-FNA, 67% and 80% for CTC, 65% and 75% for ctDNA and 79% and 93% for CA19.9, respectively. The positivity of at least 2 markers was associated with a sensitivity and specificity of 78% and 91%, respectively. CtDNA was the only marker associated with overall survival (median 5.2 months for ctDNA+ vs 11.0 months for ctDNA-, P=0.01). CONCLUSIONS: CA19.9 alone and in combination with ctDNA and/or CTC analysis may represent an efficient method for diagnosing PA in patients with SPTs. Further studies including a larger cohort of patients with both malignant and benign lesions will be necessary to confirm these promising results.

Complete endoscopic sphincterotomy with vs. without large-balloon dilation for the removal of large bile duct stones: randomized multicenter study.

Background and study aims Endoscopic sphincterotomy plus large-balloon dilation (ES-LBD) has been reported as an alternative to endoscopic sphincterotomy for the removal of bile duct stones. This multicenter study compared complete endoscopic sphincterotomy with vs. without large-balloon dilation for the removal of large bile duct stones. This is the first randomized multicenter study to evaluate these procedures in patients with exclusively large common bile duct (CBD) stones. Methods Between 2010 and 2015, 150 patients with one or more common bile duct stones ≥ 13 mm were randomized to two groups: 73 without balloon dilation (conventional group), 77 with balloon dilation (ES-LBD group). Mechanical lithotripsy was subsequently performed only if the stones were too large for removal through the papilla. Endoscopic sphincterotomy was complete in both groups. Patients could switch to ES-LBD if the conventional procedure failed. Results There was no between-group difference in number and size of stones. CBD stone clearance was achieved in 74.0 % of patients in the conventional group and 96.1 % of patients in the ES-LBD group (P < 0.001). Mechanical lithotripsy was needed significantly more often in the conventional group (35.6 % vs. 3.9 %; P < 0.001). There was no difference in terms of morbidity (9.3 % in the conventional group vs. 8.1 % in the ES-LBD group; P = 0.82). The cost and procedure time were not significantly different between the groups overall, but became significantly higher for patients in the conventional group who underwent mechanical lithotripsy. The conventional procedure failed in 19 patients, 15 of whom underwent a rescue ES-LBD procedure that successfully cleared all stones. Conclusions Complete endoscopic sphincterotomy with large-balloon dilation for the removal of large CBD stones has similar safety but superior efficiency to conventional treatment, and should be considered as the first-line step in the treatment of large bile duct stones and in rescue treatment.Trial registered at ClinicalTrials.gov (NCT02592811).

A novel hemostatic powder for upper gastrointestinal bleeding: a multicenter study (the "GRAPHE" registry).

Background and study aims: The hemostatic powder TC-325 (Hemospray; Cook Medical, Winston-Salem, North Carolina, USA) has shown promising results in the treatment of upper gastrointestinal bleeding (UGIB) in expert centers in pilot studies. The aim of this study was to evaluate the feasibility and efficacy of TC-325 in a large prospective registry of use in routine practice. Patients and methods: The data of all patients treated with TC-325 were prospectively collected through a national registry. Outcomes were the immediate feasibility and efficacy of TC-325 application, as well as the rates of rebleeding at Day 8 and Day 30. Multivariate analysis was performed to determine predictive factors of rebleeding. Results: A total of 202 patients were enrolled and 64 endoscopists participated from 20 centers. TC-325 was used as salvage therapy in 108 patients (53.5 %). The etiology of bleeding was an ulcer in 75 patients (37.1 %), tumor in 61 (30.2 %), postendoscopic therapy in 35 (17.3 %), or other in 31 (15.3 %). Application of the hemostatic powder was found to be very easy or easy in 31.7 % and 55.4 %, respectively. The immediate efficacy rate was 96.5 %. Recurrence of UGIB was noted at Day 8 and Day 30 in 26.7 % and 33.5 %, respectively. Predictive factors of recurrence at Day 8 were melena at initial presentation and use of TC-325 as salvage therapy. Conclusion: These multicenter data confirmed the high rate of immediate hemostasis, excellent feasibility, and good safety profile of TC-325, which could become the treatment of choice in bleeding tumors or postendoscopic bleeding but not in bleeding ulcers where randomized studies are needed. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02595853).

Enteral glutamine infusion modulates ubiquitination of heat shock proteins, Grp-75 and Apg-2, in the human duodenal mucosa.

Glutamine, the most abundant amino acid in the human body, plays several important roles in the intestine. Previous studies showed that glutamine may affect protein expression by regulating ubiquitin-proteasome system. We thus aimed to evaluate the effects of glutamine on ubiquitinated proteins in human duodenal mucosa. Five healthy male volunteers were included and received during 5 h, on two occasions and in a random order, either an enteral infusion of maltodextrins alone (0.25 g kg(-1) h(-1), control), mimicking carbohydrate-fed state, or maltodextrins with glutamine (0.117 g kg(-1) h(-1), glutamine). Endoscopic duodenal biopsies were then taken. Total cellular protein extracts were separated by 2D gel electrophoresis and analyzed by an immunodetection using anti-ubiquitin antibody. Differentially ubiquitinated proteins were then identified by liquid chromatography-electrospray ionization MS/MS. Five proteins were differentially ubiquitinated between control and glutamine conditions. Among these proteins, we identified two chaperone proteins, Grp75 and hsp74. Grp75 was less ubiquitinated after glutamine infusion compared with control. In contrast, hsp74, also called Apg-2, was more ubiquitinated after glutamine. In conclusion, we provide evidence that glutamine may regulate ubiquitination processes of specific proteins, i.e., Grp75 and Apg-2. Grp75 has protective and anti-inflammatory properties, while Apg-2 indirectly regulates stress-induced cell survival and proliferation through interaction with ZO-1. Further studies should confirm these results in stress conditions.

Radiofrequency ablation for the treatment of gastric antral vascular ectasia.

BACKGROUND AND STUDY AIMS: The traditional endoscopic treatment for gastric antral vascular ectasia (GAVE) is argon plasma coagulation, but results are not always positive. Radiofrequency ablation (RFA) is a new endoscopic therapy that may be an attractive option for the treatment of GAVE. The aim of this study was to assess the efficacy and safety of RFA for the treatment of GAVE. PATIENTS AND METHODS: This was an open-label, retrospective, case series study. The main outcome measures were number of red blood cell (RBC) packs transfused (transfusion requirement) and hemoglobin concentrations (g/dL) in the 6 months prior to and after RFA. Success was defined as a decrease in transfusion requirement in the 6 months after RFA compared with before treatment. RESULTS: A total of 24 patients underwent a mean of 1.8 ± 0.8 RFA sessions. No complications were reported. One patient was referred for additional argon plasma coagulation during follow-up. The mean number of RBC packs decreased in all 23 transfusion-dependent patients, from a mean of 10.6 ± 12.1 during the 6 months prior to RFA, to a mean of 2.5 ± 5.9 during the 6 months after RFA treatment (P < 0.001), and 15 patients (65.2 %) were weaned off transfusions completely. An increase in the hemoglobin concentration was reported in all patients after RFA (from 6.8 ± 1.4 g/dL to 9.8 ± 1.8 g/dL; P < 0.001). CONCLUSION: RFA for the treatment of GAVE seems feasible and safe, and significantly reduced the need for RBC transfusion and increased the hemoglobin level in this retrospective case series.

Factors associated with diagnosis of obscure gastrointestinal bleeding by video capsule enteroscopy.

BACKGROUND & AIMS: Capsule enteroscopy (CE) is the best noninvasive tool to explore the entire small bowel of patients with obscure gastrointestinal bleeding (OGIB); it has a diagnostic yield of 40%-80%. However, little is known about the factors associated with a diagnosis of OGIB by CE. METHODS: We analyzed data from 911 consecutive patients who underwent CE for OGIB from January 2004 to January 2010. Results from upper and lower gastrointestinal endoscopy examinations were negative in all patients. CE findings were recorded. Features of patients that were associated with diagnosis of OGIB by CE were identified by using logistic regression. RESULTS: Based on CE, 509 patients (56%) had a confirmed lesion responsible for the OGIB: 203 had disease of the small bowel (22%), 88 had ulcerations (10%), 70 had tumors (8%), 24 had varices (2%), 6 had diverticula (0.5%), and 118 had what appeared to be bleeding lesions of the esophagus or stomach (10.6%) or colon (2%). Factors independently associated with a diagnosis of OGIB by CE were age >60 years (odds ratio [OR], 1.2), male sex, history of overt bleeding (OR, 3.8), and current hospitalization (OR, 1.4). Women were less likely to be diagnosed with OGIB by CE (OR, 0.7). CONCLUSIONS: A history of overt bleeding is the factor most strongly associated with a diagnosis of OGIB by CE. Male sex, age >60 years, and inpatient status were also independent predictors of positive diagnosis by CE.

The expression and the cellular distribution of the tight junction proteins are altered in irritable bowel syndrome patients with differences according to the disease subtype.

OBJECTIVES: Recent studies have suggested that an increased intestinal permeability is involved in the pathophysilogy of irritable bowel syndrome (IBS). However, the differential expression of tight junctions (TJs) proteins according to IBS subtypes and symptoms remained unknown. The objective of this study was to study zonula occludens-1 (ZO-1), occludin, and claudin-1 in the colonic mucosa of patients with IBS. METHODS: Fifty IBS patients fulfilling the Rome III criteria and 31 controls were included. All types of IBS patients participated with predominant diarrhea (IBS-D, n=19), predominant constipation (IBS-C, n=14), constipation alternating with diarrhea (IBS-A, n=15), or unclassified (IBS-U, n=2). IBS symptom intensity was quantified on 10-cm Visual Analog Scale (VAS). TJ proteins (claudin-1, ZO-1, occludin) were quantified by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), western blot, while their localization was determined by immunofluorescence. RESULTS: ZO-1 and occludin expression was lower in IBS patients compared with controls, whereas only a trend for a decrease of claudin-1 was observed. The mRNA levels remained unaffected. In the subgroup analyses, occludin and claudin-1 expression was decreased in IBS-D patients but not in IBS-C and IBS-A patients. The subcellular distribution of these three proteins was altered in IBS-C and IBS-D patients. Occludin (r=0.40, P<0.01) and claudin-1 (r=0.46, P<0.01) expression was correlated with the duration of symptoms. The expression of occludin was lower in patients with an abdominal pain intensity higher than 6 on the VAS (P<0.05). CONCLUSIONS: Occludin and claudin-1 appeared markedly affected in IBS-D patients. In addition, our results suggest that alteration of TJ proteins may be involved in the initiation of IBS and contribute to visceral hypersensitivity.

Increased proteasome-mediated degradation of occludin in irritable bowel syndrome.

OBJECTIVES: Proteasome-mediated protein degradation may contribute to the regulation of intestinal inflammation. At the same time, low-grade inflammation and increased intestinal permeability seem to be involved in the pathophysiology of irritable bowel syndrome (IBS). Thus, we aimed to evaluate proteasome composition and activities in colonic mucosa of IBS patients and its putative pathogenic role. METHODS: Proteasome activities and proteasome subunit expression were measured in colonic mucosa of IBS, Crohn's disease (CD), and control patients by fluorometric assays and western blot, respectively. Expression of inhibitor of kappa B factor (IkappaB alpha) and occludin, a tight junction protein, was also evaluated in colonic biopsies. The degradation of recombinant occludin incubated with protein extracts from colonic mucosa was evaluated in the presence or absence of proteasome inhibitor, MG132. RESULTS: Proteasome trypsin-like activity was increased in IBS patients compared with CD and controls, whereas chymotrypsin-like activity was upregulated in CD patients only. Caspase-like activity was reduced both in IBS and CD patients. IkappaB alpha expression was similar between IBS and controls. In contrast, occludin expression was lower in IBS than in controls, but occludin mRNA level was similar. Protein extracts from IBS patients but not from controls degraded recombinant occludin (20% over 160 min), which was blocked by MG132. Although mast cell number was increased in IBS patients, no correlation was found between this number and proteasome alterations. CONCLUSIONS: Our study shows that proteasome alterations are present in the colonic mucosa of IBS patients and may contribute to the pathophysiology of IBS by increasing occludin degradation.

Safety of Endoscopic Ultrasound-Guided Fine-Needle Aspiration for Pancreatic Solid Pseudopapillary Neoplasm Before Surgical Resection: A European Multicenter Registry-Based Study on 149 Patients.

OBJECTIVES: The results of only a few endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for pancreatic solid pseudopapillary neoplasm (SPN) have been published, and the safety of the procedure has never been investigated. Our study compared the recurrence rate in patients with and without preoperative EUS-FNA. METHODS: This European multicenter registry-based study was conducted in 22 digestive units, and retrospectively included all patients who underwent complete resection of a pancreatic SPN from 2000 to 2018. Patients with and without initial EUS-FNA were compared, and postsurgery recurrence and the associated risk factors were evaluated. RESULTS: A complete resection of a pancreatic SPN was performed in 149 patients (133 women, 89%), with a mean age of 34 (standard deviation, 14) years. There were no significant differences between the with (78 patients) and without (71 patients) EUS-FNA groups, except for age and tumor size and location.Preoperative EUS-FNA allowed pancreatic SPN diagnosis in 63/78 cases (81%). After a mean follow-up of 43 (standard deviation, 36) months, recurrence was noted in 4 patients (2.7%). Preoperative EUS-FNA was not correlated with recurrence, but an older age (P = 0.005) was significant. CONCLUSIONS: Preoperative EUS-FNA does not affect pancreatic SPN recurrence. In this series, old age was significantly correlated with recurrence.

CAD-CAP: a 25,000-image database serving the development of artificial intelligence for capsule endoscopy.

Background and study aims Capsule endoscopy (CE) is the preferred method for small bowel (SB) exploration. With a mean number of 50,000 SB frames per video, SBCE reading is time-consuming and tedious (30 to 60 minutes per video). We describe a large, multicenter database named CAD-CAP (Computer-Assisted Diagnosis for CAPsule Endoscopy, CAD-CAP). This database aims to serve the development of CAD tools for CE reading. Materials and methods Twelve French endoscopy centers were involved. All available third-generation SB-CE videos (Pillcam, Medtronic) were retrospectively selected from these centers and deidentified. Any pathological frame was extracted and included in the database. Manual segmentation of findings within these frames was performed by two pre-med students trained and supervised by an expert reader. All frames were then classified by type and clinical relevance by a panel of three expert readers. An automated extraction process was also developed to create a dataset of normal, proofread, control images from normal, complete, SB-CE videos. Results Four-thousand-one-hundred-and-seventy-four SB-CE were included. Of them, 1,480 videos (35 %) containing at least one pathological finding were selected. Findings from 5,184 frames (with their short video sequences) were extracted and delimited: 718 frames with fresh blood, 3,097 frames with vascular lesions, and 1,369 frames with inflammatory and ulcerative lesions. Twenty-thousand normal frames were extracted from 206 SB-CE normal videos. CAD-CAP has already been used for development of automated tools for angiectasia detection and also for two international challenges on medical computerized analysis.

Nonoperable patients with superficial esophageal cancer treated by photodynamic therapy after chemoradiotherapy have more severe complications than patients treated in primary intent.

INTRODUCTION: Photodynamic therapy (PDT) is a therapeutic option in patients with a superficial esophageal cancer. Recently, PDT was shown to be effective as a salvage therapy for a local recurrence after chemoradiotherapy (CRT). AIM: To compare retrospectively the results and the complications rate of PDT between consecutive patients treated in primary intent for a superficial esophageal cancer versus patients treated by PDT for a local recurrence after CRT. METHODS: Between 1999 and 2007 in a single center, 40 consecutive patients were treated by PDT for a superficial esophageal cancer, 25 (group 1) in primary intent and 15 (group 2) for a local recurrence after CRT. Two days after intravenous (IV) Photofrin (2 mg/kg), the phototherapy was performed with a dye laser. The treatment response and severe complications, defined as perforation and stricture requiring endoscopic dilation, were compared between the two groups. RESULTS: The patient and tumor characteristics were not different between the two groups. In group 1, 19 out of 25 patients (76%) were successfully treated versus 8 out of 15 patients (53%) in group 2 (P= 0.17). Severe complications occurred more frequently in patients with a prior CRT (8%vs 46.7%, P= 0.008) and included two perforations and five strictures requiring endoscopic dilation, while only two strictures occurred in group 1. A prior CRT was an independent risk factor of severe complications (odds ratio [OR] 8.05; 95% confidence interval [CI]1.22-43.0). CONCLUSIONS: Severe complications were significantly more frequent in patients treated after a prior CRT. PDT as a salvage therapy in patients with a local recurrence after CRT for esophageal cancer tended to be less efficient than in first-line treatment.

Combined glutamine and arginine decrease proinflammatory cytokine production by biopsies from Crohn's patients in association with changes in nuclear factor-kappaB and p38 mitogen-activated protein kinase pathways.

Glutamine (Gln) and arginine (Arg) are conditionally essential amino acids with immunomodulatory properties. The aim of the study was to assess the effects of Gln and Arg alone or in combination on cytokine release by cultured colonic biopsies from patients with active Crohn's disease (CD). Ten consecutive patients [mean (range) age 26 (18-39) y] with active colonic CD (mean CD activity index: 383.7 +/- 129.8) were prospectively included in the study. Eight colonic biopsies were obtained via a colonoscopy and incubated during 18 h with low (physiological) or high (pharmacological) doses of Arg (0.1 or 2 mmol/L designated as Arg(low) or Arg(high), respectively) and Gln (0.6 or 10 mmol/L designated as Gln(low) or Gln(high), respectively). The concentrations of cytokines [interleukin (IL)-4, IL-10, IL-8, IL-6, tumor necrosis factor-alpha (TNFalpha), IL-1beta, interferon-gamma) were assessed by ELISA, and nitric oxide (NO) production was evaluated by Griess assay. Nuclear factor (NF)-kappaB p65 subunit, inhibitor of NFkappaB-alpha, and p38 mitogen-activated protein kinase (MAPK) were assessed by immunoblotting. Arg(high)/Gln(high) decreased the production of TNFalpha, IL-1beta, IL-8, and IL-6 (each P < 0.01). Arg(low)/Gln(high) decreased IL-6 and IL-8 production (both P < 0.01), whereas Arg(high)/Gln(low) did not affect cytokine and NO production. Arg(low)/Gln(high) and Arg(high)/Gln(high) decreased NF-kappaB p65 subunit expression, whereas p38 MAPK was decreased only by Arg(high)/Gln(high). Combined pharmacological doses of Arg and Gln decreased TNFalpha and the main proinflammatory cytokines release in active colonic CD biopsies via NF-kappaB and p38 MAPK pathways. These results could be the basis of prospective studies evaluating the effects of enteral supply of combined Arg and Gln during active CD.

Duodenal intraepithelial T lymphocytes in patients with functional dyspepsia.

AIM: To quantify the intraepithelial lymphocytes (IELs) and to document the membrane expression of CD4, CD8, TCRgamma delta and adhesion and/or activation-associated molecules (CD103, CD28, CD44, CD69, HLA-DR, CD95/Fas) in the duodenal mucosa of patients with functional dyspepsia (FD) in order to provide arguments for an immunological process in FD. METHODS: Twenty-six FD patients according to Rome II criteria (20 were H pylori negative) were studied and compared to 12 healthy adults. IELs were isolated from five duodenal biopsy samples, then quantified by microscopy and flow cytometry while the membrane phenotypes were determined by cytofluorometry. RESULTS: Duodenal histological examination was normal. In H pylori negative patients, the number of IELs was not different from that in healthy controls. Median percentage expression of CD4, CD8, or TCRgamma delta and CD103, CD44, CD28, CD69 on CD3+ IELs, among the adhesion/activation associated molecules tested, was not different from that in healthy controls. In contrast, the median percentage expression of CD95/Fas [22 (9-65) vs 45 (19-88), P=0.03] and HLA-DR expressing CD3+ IELs [4 (0-30) vs 13 (4-42), P=0.04] was significantly lower in the H pylori negative FD group than in healthy controls, respectively. The number of IELs was significantly greater in H pylori positive FD patients than in healthy controls [median ratio for 100 enterocytes 27.5 (6.7-62.5) vs 10.8 (3-33.3), P=0.02] due to a higher number of CD8+ CD3+ IELs. CONCLUSION: In H pylori negative FD patients, the phenotypic characterization of IELs suggests that we cannot exclude a role of IELs in FD.

Predictive factors of survival in patients treated with definitive chemoradiotherapy for squamous cell esophageal carcinoma.

AIM: The aim of the study was to evaluate the predictive factors of survival in patients with locally advanced squamous cell esophageal carcinoma (LASCOC) treated with definitive chemoradiotherapy (CRT) regimen based on the 5FU/CDDP combination. METHODS: All patients with LASCOC treated with a definitive CRT using the 5FU/CDDP combination between 1994 and 2000 were retrospectively included. Clinical complete response (CCR) to CRT was assessed by esophageal endoscopy and CT-scan 2 mo after CRT completion. Prognostic factors of survival were assessed using univariate and multivariate analysis by the Cox regression model. RESULTS: A total of 116 patients were included in the study. A CCR to CRT was observed in 86/116 (74.1%). The median survival was 20 mo (range 2-114) and the 5-year survival was 9.4%. Median survival of responder patients to CRT was 25 mo (range 3-114) as compared to 9 mo (range 2-81) in non-responder patients (P < 0.001). In univariate analysis, survival was associated with CCR (P < 0.001), WHO performance status < 2 (P = 0.01), tumour length < 6 cm (P = 0.045) and weight loss < 10% was in limit of significance (P = 0.053). In multivariate analysis, survival was dependant to CCR (P < 0.0001), weight loss < 10% (P = 0.034) and WHO performance < 2 (P = 0.046). CONCLUSION: Our results suggest that survival in patients with LASCOC treated with definitive CRT was correlated to CCR, weight loss and WHO performance status.

Impact of radiation schedule and chemotherapy duration in definitive chemoradiotherapy regimen for esophageal cancer.

UNLABELLED: Impact of radiotherapy (RT) schedule on local response and duration of the 5-fluorouracil/cisplatin (5 FU/CDDP) chemotherapy (CT) on m are still questioning in chemoradiotherapy (CRT) regimen in esophageal carcinoma. AIM: Evaluate two RT schedules and two different CT durations by a retrospective comparison of the CRT regimens used by two centres between 1994 and 2000. METHODS: In centre I (regimen I), patients received 2 CT concomitantly to a continuous RT (50 Gy/25 fractions/5 weeks). In centre II (regimen II), patients received 6 CT, 3 were concomitant to a split course RT (20 Gy/10 fractions x 3 courses) and 3 CT were delivered after CRT. RESULTS: A total of 129 patients were included, 74 in centre I and 55 in centre II respectively. Main patient characteristics were similar between the two groups. Clinical complete response to CRT was significantly more frequent in regimen I (83.8% vs 65.4%; P=0.02). The median overall survival (OS) was 20 months in regimen I and 22 months in regimen II (NS). During follow-up, responder patients to CRT in regimen II experienced significant fewer metastasis (51.6% vs 27.8%; P=0.03) with a trend to an increased 5-year survival (19.4% vs 11.3%) and OS (26.5 vs 21.0 months) (NS). Grade 3-4 toxicities were not different. CONCLUSION: Clinical complete response to CRT was significantly more frequent with a continuous RT whereas additional CT after CRT significantly reduced metastasis occurrence. CRT regimen in esophageal carcinoma may be more effective using a continuous RT schedule and additional CT courses after CRT completion.

Modulation of nitric oxide and cytokines production by L-arginine in human gut mucosa.

BACKGROUND: Arginine is a conditionally essential amino-acid with immuno-modulatory properties, mainly through the nitric oxide (NO) pathway. AIM: To assess the effects of arginine on intestinal production of pro- and anti-inflammatory cytokines and NO in human gut. METHODS: An enteral solution of arginine or a control solution of amino-acids was administered to 8 healthy volunteers on a randomized cross-over design. Duodenal biopsies were taken. Pro- (IL-6, IL-8) and anti-inflammatory (IL-4, IL-10) cytokines mRNA expression was assessed by RT-PCR. Other biopsies were cultured with 0.1, 0.5 or 2 mM arginine or control amino-acids, under basal or IL-1beta-induced inflammatory conditions. Interleukin-4, IL-6, IL-8 and IL-10 production was measured in culture supernatant by ELISA and NO production by Griess reaction. RESULTS: Arginine enhanced the production of NO under inflammatory conditions in a dose-dependent manner (P=0.03). IL-1beta increased the production of IL-8 and IL-6 (P<0.01). Arginine had no effect on pro- and anti-inflammatory cytokines production both under basal and inflammatory conditions. CONCLUSIONS: Arginine enhanced the production of NO but did not affect that of cytokines in inflammatory human gut. Further clinical studies are required to assess whether arginine-enhanced NO production plays a beneficial or deleterious effect in intestinal inflammation.

Changes in characteristics and outcome of acute upper gastrointestinal haemorrhage: a comparison of epidemiology and practices between 1996 and 2000 in a multicentre French study.

OBJECTIVE: To evaluate the main changes in characteristics, practices and outcome between 1996 and 2000 in patients admitted for an acute upper gastrointestinal haemorrhage (AUGIH). PATIENTS AND METHODS: All consecutive patients (n=1165) admitted for an AUGIH in four French administrative areas were entered into two separate 6-month studies conducted in 1996 (n=712) and 2000 (n=453). Epidemiological and biological characteristics, endoscopic haemostatic procedures and outcomes were compared. RESULTS: Patient characteristics remained unchanged between the two studies; the two main bleeding lesions were peptic ulcer and oesophagogastric varices (30.2 versus 31.1% and 22.5 versus 20.3%). The use of non-steroidal anti-inflammatory drugs or aspirin was more frequent in 2000 (26.5 versus 32.6%; P<0.03). Proton pump inhibitor preventative therapy was administered in less than 15% of patients with a high risk of peptic ulcer bleeding in each period. In patients admitted for varices bleeding, the use of endoscopic haemostatic ligation increased (17.1 versus 40%; P<0.001), with a concomitant decrease in endoscopic sclerotic therapy (76.1 versus 37.5%; P<0.001). We observed a significant decrease in AUGIH mortality in the whole group (11.7 versus 7.2%; P=0.03), and particularly in the subgroup of cirrhotic patients (19.5 versus 11.1%; P=0.05) whatever the source of their bleeding. CONCLUSION: Our time-trend evaluation of changes in AUGIH characteristics revealed that peptic ulcer and varices were still the two most frequent bleeding lesions. In patients with varices bleeding, endoscopic ligation became the routine standard treatment instead of varices sclerosis. The mortality rate decreased significantly over the 5-year study period in the whole group and particularly in the subgroup of cirrhotic patients.