Baseline HBsAg and HBcrAg titres allow peginterferon-based 'precision medicine' in HBeAg-negative chronic hepatitis B patients.

Quantitative hepatitis B core-related antigen (qHBcrAg) has been proposed as an additional marker to quantitative HBsAg (qHBsAg), for management of chronic hepatitis B. Evaluate baseline combination of qHBsAg and qHBcrAg for identification of patients that could benefit from pegylated interferon-alpha-2a (PegIFN)-based therapy. Sixty-two HBeAg-negative patients treated with PegIFN or PegIFN plus tenofovir disoproxil fumarate (PegIFN+TDF). HBsAg and HBcrAg titres were evaluated at baseline. Thirty patients received PegIFN and 32 PegIFN+TDF. SR was 10 of 30 and 17 of 32 in PegIFN and PegIFN+TDF patients, respectively. Cut-offs determined by maximized Youden's index for identifying patients likely to respond to therapy were as follows: 3.141 log10 IU/mL and 3.450 log10 U/mL for HBsAg and HBcrAg, respectively. At the end of 3 years post-treatment follow-up, HBsAg loss was observed in 7 of 30 and 6 of 32 in PegIFN and PegIFN+TDF patients, respectively. The AUC was estimated to be 0.716 (95% CI [0.578, 0.855]) for HBsAg and 0.668 (95% CI [0.524, 0.811]) for HBcrAg (P=.5541). PPVs for AUCs(95%CI) were 0.762(0.590-0.947), 0.714(0.533-1.000) and 0.800(0.611-1.000), and NPVs for AUCs(95%CI) were 0.756(0.660-0.899), 0.718(0.630-0.857) and 0.765(0.675-0.889) for qHBsAg, qHBcrAg and the combination of both markers, respectively. Baseline qHBsAg 3.141 log10 IU/mL and qHBcrAg 3.450 log10 U/mL thresholds used separately or in combination allow prediction of response, prior to PegIFN-based therapy, with a PPV of 80.3% and NPV of 76.5%. Baseline qHBsAg is predictive of HBsAg loss. Both markers could be used, separately or in combination, for PegIFN-based 'precision therapy'. Our results emphasize that the combination of PegIFN alpha-2a plus TDF with 53% of SR might be an alternative to finite therapy.

IFNL3 (IL28B) polymorphism does not predict long-term response to interferon therapy in HBeAg-positive chronic hepatitis B patients.

UNLABELLED: The impact of IFNL3 (IL28B) polymorphism on response to interferon (IFN) treatment in patients infected with hepatitis B virus (HBV) is controversial. We aimed to investigate whether IFNL3 polymorphism (rs12979860) influences the long-term response of chronic hepatitis B (CHB) treatment to conventional IFN. DESIGN: Ninety-seven HBeAg-positive patients treated with IFN were evaluated in this study. Associations were investigated between IFNL3 genotypes and (i) HBeAg seroconversion at the end of treatment (EOT), (ii) sustained virological response (SVR) and (iii) HBsAg seroconversion through long-term follow-up (LTFU). Patients were followed for a median of 14 years. The majority of patients were infected with HBV genotype A (69.6%) and were Caucasian (77.9%). Ninety-five patients were genotyped at rs12979860. Similar IFNL3 distribution was observed among the different ethnicities (P = 0.62) or across HBV genotypes A through G (P = 0.70). Thirty-six patients experienced HBeAg seroconversion at EOT; HBeAg seroconversion rates were 37.0 and 35.5% in patients with CC and CT/TT genotypes, respectively (P = 0.82). Among the 44 patients (45%) who achieved a SVR, SVR rates were 48.9 and 39.6% in patients with CC and CT/TT IL28B genotypes, respectively (P = 0.80). HBsAg seroconversion occurred through LTFU in 28 patients. HBsAg seroconversion rates were 25.5 and 31.2% in patients with CC and CT/TT genotypes, respectively (P = 0.51). No significant relationship between IFNL3 rs12979860 and fibrosis stage was observed (P = 0.85). IFNL3 genotype was neither associated with SVR, nor with HBeAg seroconversion and long-term HBsAg seroconversion in HBeAg-positive CHB patients responding to IFN therapy.

Phylogeography of Francisella tularensis ssp. holarctica in France.

AIM: To investigate the phylogeography of French Francisella tularensis ssp. holarctica isolates. METHODS AND RESULTS: Canonical SNPs and MLVA were used to genotype 103 French F. tularensis ssp. holarctica isolates. We confirmed the presence of one subclade, the central and western European group (B.Br.FTNF002-00), and identified four major MLVA genotypes with no obvious geographical differentiation. CONCLUSIONS: The lack of geographical resolution among MLVA genotypes suggests rapid dispersal, convergent evolution or a combination of the two. SIGNIFICANCE AND IMPACT OF THE STUDY: This study expands knowledge of the phylogeography of one of the two dominant European F. tularensis ssp. holarctica subclades and illustrates the need for additional SNP discovery within this subclade.

Diagnostic accuracy of esophageal capsule endoscopy versus conventional upper digestive endoscopy for suspected esophageal squamous cell carcinoma.

BACKGROUND AND STUDY AIM: A video capsule similar to that used in small-bowel capsule endoscopy is now available for esophageal exploration. The aim of our study was to compare the accuracy of upper endoscopy (esophageal gastroduodenoscopy [EGE]) with esophageal capsule endoscopy (ECE) in patients at risk of esophageal squamous cell cancer (SCC). PATIENTS AND METHODS: 68 patients at risk of SCC secondary to a history of head and neck neoplasia were included in this comparison of techniques for detecting SCC and dysplasia. ECE was done using the first generation Pillcam ESO and EGE was performed in accordance with the usual practice of each center, followed by examination with 2 % Lugol staining and biopsy of unstained areas (39 neoplasia comprising 5 low grade dysplasia, 8 high grade dysplasia and 26 SCC). RESULTS: Compared with EGE with and without Lugol staining, the sensitivities of ECE for neoplasia diagnosis were 46 % and 54 %, respectively. On a per-patient basis, the sensitivity, specificity, and positive and negative predictive value of ECE were 63 %, 86 %, 77 % and 76 %, respectively, compared with EGE without staining, and 61 %, 86 %, 77 % and 73 % compared with EGE with iodine staining. Neither the ECE transit time nor the distance between the esopharyngeal line and the neoplastic lesion differed between the 21 false-negative and 18 true-positive cases diagnosed by ECE; the only difference was a smaller median diameter among false negatives ( P < 0.001). CONCLUSION: In a cohort at high risk for esophageal SCC, ECE is not sensitive enough to diagnose neoplastic lesions.

Esophageal capsule endoscopy vs. EGD for the evaluation of portal hypertension: a French prospective multicenter comparative study.

OBJECTIVES: Esophagogastroduodenoscopy (EGD) is the standard method for the diagnosis of esophago-gastric varices. The aim of this prospective multicenter study was to evaluate the PillCam esophageal capsule endoscopy (ECE) for this indication. METHODS: Patients presenting with cirrhotic or noncirrhotic portal hypertension underwent ECEfollowed by EGD at the time of diagnosis. Capsule recordings were blindly read by two endoscopists. RESULTS: A total of 120 patients (72 males, mean age: 58 years; mean Child-Pugh score: 7.2) were included. Esophageal varices were detected in 74 patients. No adverse event was observed after either EGD or ECE. Seven (6%) patients were unable to swallow the capsule. The mean recording time was 204 s (range 1-876). Sensitivity, specificity, negative predictive value, and positive predictive value of ECE for the detection of esophageal varices were 77%, 86%, 69%, and 90%, respectively. Sensitivity, specificity, negative and positive predictive values of ECE for the indication of primary prophylaxis (esophageal varices > or = grade 2 and/or red signs) were 77, 88, 90, and 75%, respectively, and 85% of the patients were adequately classified for the indication (or not) of prophylaxis. Interobserver concordance for ECE readings was 79.4% for the diagnosis of varices, 66.4% for the grading of varices, and 89.7% for the indication of prophylaxis. CONCLUSIONS: This large multicenter study confirms the safety and acceptable accuracy of ECE for the evaluation of esophageal varices. ECE might be proposed as an alternative to EGD for the screening of portal hypertension, especially in patients unable or unwilling to undergo EGD.

Frequency and severity of ileal adenomas in familial adenomatous polyposis after colectomy.

BACKGROUND AND STUDY AIMS: The high cumulative risk of colorectal cancer in patients with familial adenomatous polyposis (FAP) justifies prophylactic colectomy with either ileorectal (IRA) or ileal-pouch-anal anastomosis (IPAA). Our aim was to evaluate retrospectively the frequency of and time interval to adenoma development in the ileal mucosa of patients with both types of surgery. PATIENTS AND METHODS: Retrospective study of 44 FAP patients with IRA (n = 21) and IPAA (n = 23). All patients were followed with a standardized procedure including chromoscopy and biopsies of visible polyps. In patients with IRA, specific attention was paid to the ileal mucosa above the anastomosis. RESULTS: In the IPAA group, 18/23 patients (78 %) presented with visible polyps [histology: 16 (70 %) had adenoma with low-grade dysplasia; 1 (4 %) had adenoma with high-grade dysplasia; 1 had normal mucosa]. The mean interval between colectomy and the diagnosis of adenoma was 4.7 +/- 3.3 years. In the IRA group, 16/21 patients (77 %) presented visible polyps in the ileal mucosa [adenoma with low-grade dysplasia in 8 patients (38 %), with high-grade dysplasia in 2 (10 %), and lymphoid nodular hyperplasia in 6]. The mean interval between colectomy and adenoma diagnosis was significantly shorter in the IPAA than in the IRA group (4.76 +/- 3.3 vs. 16.4 +/- 8.5 years, P< 0.0001). CONCLUSION: Our results show a high frequency of adenomas in the ileal mucosa of patients with IPAA and IRA (74 % and 48 % respectively), with evolution into high-grade dysplasia in 6.7 % of cases.

Miss rate for colorectal neoplastic polyps: a prospective multicenter study of back-to-back video colonoscopies.

BACKGROUND AND STUDY AIM: Polyp miss rates during colonoscopy have been calculated in a few tandem or back-to-back colonoscopy studies. Our objective was to assess the adenoma miss rate while limiting technique or operator expertise biases, i. e. by performing a large multicenter study, with same-day back-to-back video colonoscopy, done by two different operators in randomized order and blinded to the other examination. PATIENTS AND METHODS: 294 patients at 11 centers were included. Among the 286 analyzable tandem colonoscopies, miss rates were calculated in both a lesion- and patient-based analysis. Each of these rates was determined for polyps overall, for adenomas, and then for lesions larger than 5 mm, and for advanced adenomas. Univariate and logistic regression analysis were performed to define independent variables associated with missed polyps or adenomas. RESULTS: The miss rates for polyps, adenomas, polyps > or = 5 mm, adenomas > or = 5 mm, and advanced adenomas were, respectively, 28 %, 20 %, 12 %, 9 % and 11 %. None of the masses with a carcinomatous (n = 3) or carcinoid component (n = 1) was missed. The specific lesion miss rates for patients with polyps and adenomas were respectively 36 % and 26 % but the corresponding rates were 23 % and 9.4 % when calculated for all 286 patients. The diameter (1-mm increments) and number of polyps (> or = 3) were independently associated with a lower polyp miss rate, whereas sessile or flat shape and left location were significantly associated with a higher miss rate. Adequacy of cleansing, presence of diverticula, and duration of withdrawal for the first procedure were not associated with adenoma miss rate. CONCLUSIONS: We confirm a significant miss rate for polyps or adenoma during colonoscopy. Detection of flat polyps is an issue that must be focused on to improve the quality of colonoscopy.

A Model-Based Illustrative Exploratory Approach to Optimize the Dosing of Peg-IFN/RBV in Cirrhotic Hepatitis C Patients Treated With Triple Therapy.

Hézode et al. recently reported the frequent occurrence of anemia and thrombocytopenia in the ANRS-CO20-CUPIC cohort of hepatitis C virus (HCV) cirrhotic experienced patients treated with pegylated-interferon (Peg-IFN), ribavirin (RBV), and telaprevir or boceprevir.1,2 Using frequent measurements of serum drug concentrations, hemoglobin, and platelet concentrations obtained in 15 patients of this cohort, we show how an on-treatment model-based approach could be used to individualize dose regimen and avoid the occurrence of RBV-induced anemia and Peg-IFN-induced thrombocytopenia.

Unusual cystic presentation of an endocrine carcinoma of the jejunum.

The cystic presentation of endocrine tumours is rare and raises difficult diagnostic problems. So far, the only cases of cystic digestive endocrine tumours reported in the literature are of pancreatic origin. We report the unusual observation of a jejunal endocrine carcinoma presenting as a cystic abdominal mass. A 59-year-old woman was referred for chest and abdominal pain. Imaging studies revealed multiple cystic nodules in the liver and a large sus-mesocolic cystic lesion of probable intestinal origin. Biopsies of the extra-hepatic mass and liver nodules showed endocrine tumour. Surgical resection of the jejunal mass and of liver segment III were performed. Histological examination confirmed the diagnosis of jejunal endocrine carcinoma metastatic to the liver. Large areas of the primary and secondary tumours presented an unusual vesicular architecture, responsible for the cystic presentation. No adjuvant treatment was attempted. This observation underlines the difficult diagnostic problems raised by the cystic presentation of digestive endocrine tumours.

[Prospective randomized single-blind trial comparing oral sodium phosphate with polyethylene glycol for colonoscopy preparation]. / Etude prospective randomisée en simple aveugle comparant phosphate de sodium oral et polyéthylène glycol pour la préparation à la coloscopie.

AIM AND METHODS: The aim of this prospective, randomized, study performed in 60 outpatients was to compare 2 precolonoscopy bowel preparations: oral sodium phosphate (NaP) versus standard polyethylene glycol-based lavage solution (PEG). None of the patients met any of NaP exclusion criteria. All patients were prepared on the day prior to colonoscopy. A patient-questionnaire and measure of serum electrolytes (calcium, phosphate, sodium, potassium), pulse and blood pressure were used to assess tolerance and acceptability of the preparation. The quality of colon cleansing was judged by blinded endoscopists. RESULTS: Patient's tolerance to NaP was superior to PEG: NaP preparation was easier to drink and feelings of abdominal plenitude occurred in a smaller proportion of patients. A potassium decrease, a sodium increase and hyperphosphatemia were observed in the NaP group but without clinical events. PEG preparation seemed to allow a better cleansing ability compared with NaP but this difference was not statistically significant. CONCLUSIONS: NaP solution was better tolerated and accepted by patients. Colonic preparation quality compared to PEG is still to be discussed depending on the intake schedule. A biochemical data check seems necessary on account of significant serum electrolytes changes induced by NaP preparation.

[Enterocele: clinical risk factors and association with others pelvic floor disorders (about 544 defecographies)]. / Entérocèle: facteurs de risque clinique et associations à d'autres troubles de la statique pelvienne (à partir de 544 défécographies).

OBJECTIVE: To study, by means of defecography, clinical risk factors of enterocele and association with others pelvic floor disorders. PATIENTS AND METHODS: Five hundred and forty-four consecutive female patients were investigated by colpocystodefecography with contrast medium in the small bowel. One hundred and thirty-six women with enterocele were compared to 408 women without enterocele. RESULTS: There were no significant differences in age, obstetrical history (parity, foetal macrosomia, instrumental extractions or perineal tear to delivery) between the two groups. More women with enteroceles had histories of hysterectomies (60% versus 24%) or cystopexies (29% versus 13%). Others pelvic floor disorders were associated in 91% of enterocele: rectocele (25%), cystocele (42%), uterine prolapse (28%), rectal intussusception (52%), rectal prolapse (4%) and abnormal perineal descent (30%). Stress urinary incontinence was significantly more frequent in women without enterocele. DISCUSSION AND CONCLUSIONS: The study has demonstrated that previous hysterectomy and cystopexy increased the risk of enterocele formation and that enterocele and others pelvic floor disorders are often concomitant. Enterocele may have a pessary effect on urinary disorders. Results of colpocystodefecography reinforce the notion of pelvic floor local disease.

Endoscopic mucosal resection for squamous premalignant and early malignant lesions of the esophagus.

UNLABELLED: BACK AND STUDY AIMS: Endoscopic mucosal resection (EMR) is used to treat premalignant and malignant digestive tract lesions. This report presents the efficacy and safety of EMR for squamous superficial neoplastic esophageal lesions. PATIENTS AND METHODS: A retrospective cohort study presented data from 51 patients with 54 lesions over an 8-year period, between November 1997 and September 2005. Dysplasas or mucosal (m) T1 carcinomas were treated with repeated EMR until there was a complete local remission. Patients with submucosal (sm) T1 carcinomas were treated with repeated EMR until there was a complete local remission. Patients with submucosal (sm) T1 carcinomas or more advanced stage were offered surgery or chemoradiotherapy. RESULTS: There was no mortality, perforation, or major hemorrhage, and there were three easily dilated stenoses. Of the patients, 16 had lesions graded as T1sm or more advanced and one patient was found to have normal tissue post EMR. Complete local remission was achieved in 31 of the 34 patients with dysplasia or T1 m cancers (91%). There was no distant relapse and there was local disease recurrence in eight of the 31 patients (26%). The 5-year survival rate was 95%. CONCLUSIONS: EMR for squamous superficial neoplastic lesions of the esophagus is safe and provides satisfactory survival results.

Does chromoendoscopy with structure enhancement improve the colonoscopic adenoma detection rate?

BACKGROUND AND STUDY AIMS: Colonoscopy is still considered the standard investigation for the detection of colorectal adenomas, but the miss rate, especially for small and flat lesions, remains unacceptably high. Chromoscopy has been shown to increase the yield for lesion detection in inflammatory bowel disease. The aim of this randomized prospective study was to determine whether a combination of chromoscopy and structure enhancement could increase the adenoma detection rate in high-risk patients. PATIENTS AND METHODS: All patients included in the trial had a personal history of colorectal adenomas and/or a family history of colorectal cancer (but excluding genetic syndromes). They were randomized to one of two tandem colonoscopy groups, with the first pass consisting of conventional colonoscopy for both groups, followed by either chromoscopy and structure enhancement (the "study" group) or a second conventional colonoscopy (the control group) for the second-pass colonoscopy. All detected lesions was examined histopathologically after endoscopic resection or biopsy. The principal outcome parameter was the adenoma detection rate; the number, histopathology, and location of lesions was also recorded. RESULTS: A total of 292 patients were included in the study (146 patients in each group). The patients' demographic characteristics, the indications for colonoscopy, and the quality of bowel preparation were similar in the two groups. There was a significant difference between the two groups with respect to the median duration of the examination (18.9 minutes in the control group vs. 27.1 minutes for the study group, P < 0.001). Although more hyperplastic lesions were detected throughout the colon in the study group ( P = 0.033), there was no difference between the two groups in either the proportion of patients with at least one adenoma or in the total number of adenomas detected. Chromoscopy and structure enhancement diagnosed significantly more diminutive adenomas (< 5mm) in the right colon, compared with controls ( P = 0.039). CONCLUSIONS: On the basis of our results we cannot generally recommend the systematic use of chromoscopy and structure enhancement in a high-risk patient population, although the detection of small adenomas in the proximal colon was improved.

Esophageal capsule endoscopy versus esophagogastroduodenoscopy for evaluating portal hypertension: a prospective comparative study of performance and tolerance.

BACKGROUND AND STUDY AIMS: Esophagogastroduodenoscopy (EGD) is the most effective method for examining the upper gastrointestinal tract, and particularly for evaluating portal hypertension in cirrhotic patients, especially for screening purposes. The aim of this study was to assess the feasibility, safety, accuracy, and tolerance of PillCam ESO capsule endoscopy for this indication. PATIENTS AND METHODS: In this prospective study, unsedated EGD and capsule endoscopy examinations were conducted on the same day in cirrhotic patients at the time of diagnosis. The patients quantified the tolerability (relative to pain, nausea, choking sensations, etc.) of the two procedures using a 100-mm visual analogue scale. The time required for the recording and for diagnosis with the capsule examination were documented, as were the patients' preferences in comparison with EGD. Two independent endoscopists blinded to the EGD diagnoses assessed the diagnostic accuracy of the images obtained. RESULTS: Twenty-one patients were included in the study (mean age 62, mean Model for End-Stage Liver Disease score 10.5, mean Child-Pugh score 7.3). The procedure was safe. One patient was unable to swallow the capsule. The mean recording time was 213 s (range 6 - 1200 s); the procedure accurately assessed the presence or absence of esophageal varices in 16 of 19 patients (84.2 %); and it correctly indicated a need for primary prophylaxis (esophageal varices of grade 2 or more and/or red signs) in 100 % of cases. The tolerability of the capsule endoscopy examination was significantly better, and all of the patients preferred capsule endoscopy to EGD (which was transnasal in 11 patients). CONCLUSIONS: Capsule endoscopy was feasible, safe, accurate, highly acceptable, and preferred by cirrhotic patients undergoing screening for portal hypertension. This new technique requires further and more extensive evaluation, as well as assessment of its cost-effectiveness.