Apport de la pH-impédancemétrie au diagnostic du reflux gastro- oesophagien et de la dysphagie [Advantages of pH-impedance monitoring in gastroesophageal reflux and dysphagia investigations]

Les manifestations ORL du reflux gastro-œsophagien sont fréquentes. La pH-impédancemétrie permet d’évaluer des reflux acides ou non acides et de déterminer leur extension proximale. A la lumière de deux patients de notre collectif, nous observons une corrélation entre reflux non acide et symptômes ORL dans le premier cas et une suppression acide insuffisante dans le deuxième cas. Ces résultats nous orientent vers un traitement spécifique complémentaire aux inhibiteurs de la pompe à protons. La pH-impédancemétrie détecte les reflux aussi bien acides que non acides, et analyse la concordance entre les symptômes et les épisodes de reflux. Elle permet ainsi une meilleure compréhension des manifestations ORL du reflux gastro-œsophagien et une prise en charge thérapeutique mieux adaptée. ENT symptoms of gastro-esophageal reflux are frequent. pH-impedance can detect acid and non-acid reflux and measure their proximal extension. The technique identifies the refluxate by changes in impedance. We discuss 2 clinical situations where correlation of symptoms could be explained by a non-acid reflux in the first case, and a lack of acid suppression in the second case, respectively. These results lead to a specific additional treatment to proton pump inhibitors (PPI). This technology provides a better understanding of the pathogenesis of reflux laryngitis, and affords the prescription of PPI on a proven diagnosis. Detection of non-acid reflux leads to an optimized medical treatment.

Family history of cancer and the risk of cancer: a network of case-control studies.

BACKGROUND: The risk of many cancers is higher in subjects with a family history (FH) of cancer at a concordant site. However, few studies investigated FH of cancer at discordant sites. PATIENTS AND METHODS: This study is based on a network of Italian and Swiss case-control studies on 13 cancer sites conducted between 1991 and 2009, and including more than 12 000 cases and 11 000 controls. We collected information on history of any cancer in first degree relatives, and age at diagnosis. Odds ratios (ORs) for FH were calculated by multiple logistic regression models, adjusted for major confounding factors. RESULTS: All sites showed an excess risk in relation to FH of cancer at the same site. Increased risks were also found for oral and pharyngeal cancer and FH of laryngeal cancer (OR = 3.3), esophageal cancer and FH of oral and pharyngeal cancer (OR = 4.1), breast cancer and FH of colorectal cancer (OR = 1.5) and of hemolymphopoietic cancers (OR = 1.7), ovarian cancer and FH of breast cancer (OR = 2.3), and prostate cancer and FH of bladder cancer (OR = 3.4). For most cancer sites, the association with FH was stronger when the proband was affected at age <60 years. CONCLUSIONS: Our results point to several potential cancer syndromes that appear among close relatives and may indicate the presence of genetic factors influencing multiple cancer sites.

Pediatric and adult eosinophilic esophagitis: similarities and differences.

Early in the 1990s, several case series described adults suffering from dysphagia and children with refractory reflux symptoms, both accompanied by an eosinophil-predominant infiltration, thereby conclusively distinguishing it from gastroesophageal reflux disease. Eosinophilic esophagitis (EoE) was recognized as its own entity in the adult and in the pediatric literature. In the last decade, evidence has accumulated that EoE represents a T-helper (Th)2-type inflammatory disease. Remodeling of the esophagus is a hallmark of EoE, leading to esophageal dysfunction and bolus impaction. Familial occurrence and disease association with single-nucleotide polymorphisms underscore the influence of genetics in this disease. Eosinophilic esophagitis may affect individuals at any age, although the clinical presentation is highly age dependent. There is a significant allergic bias in the EoE population, with the majority of patients having concurrent allergic rhinitis, asthma, eczema, and/or a history of atopy. One noteworthy difference is that in children, EoE seems to be primarily a food antigen-driven disease, whereas in adults, mainly aeroallergen sensitization has been observed. Treatment modalities for EoE include the 3Ds: drugs, diet, and dilation. The crucial question of whether adult and pediatric EoE are different phenotypes of one single entity or whether we are confronted with two different diseases is still open. Here, we review similarities and differences between EoE in adults and children.

Successful bilateral lung transplantation after previous pneumonectomy

Objective: To present the feasibility of bilateral lung transplantation after previously performed pneumonectomy.Methods: A 32 years old women underwent right pneumonectomy for bronchiectasis-related destroyed lung. Eight months later, she developed a vascular post-pneumonectomy syndrome and underwent realigning of the mediastinum by an intrathoracic expander that was complicated by an adult respiratory distress syndrome of the left lung requiring mechanical ventilation, arterio-venous CO2 removal (Novalung) and finally bilateral lung transplantation. Via clamshell incision, the post-pneumonectomy cavity was dissected and the superior vena cava (SVC) and carina were exposed. The pulmonary vessel stumps were dissected intrapericardically after realization of a right-sided hemi-pericardectomy. Extracorporeal circulation was started after central cannulation of the aorta and the inferior vena cava. A right upper lobe sleeve resection of the donor lung was performed. The intermediate bronchus was then implanted in the dissected recipient carina after realization of a hilar release maneuver. The right pulmonary artery was clamped between SVC andthe ascending aorta followed by end -to-end anastomosis of the donor and recipient artery and left atrial cuffs, respectively. Satisfactory graft function allowed decanulation and standard transplantation of the left lung without extracorporeal circulation.Results: Bronchoscopy and trans-esophageal echocardiography demonstrated a patent airway and vascular anastomoses without stenosis. Follow-up revealed excellent gas exchanges, no airway complications and well-functioning grafts on both sides with right-sided ventilation and perfusion two months after transplantation of 37% and 22%, respectively.Conclusion: This is to our knowledge the first report of successful bilateral lung transplantation after previous pneumonectomy unrelated to transplantation.

What is the Omega-Loop Gastric Bypass and Why is it Criticized?

The omega-loop gastric bypass (OLGBP), also called "mini-gastric bypass" or "single-anastomosis" gastric bypass is a form of gastric bypass where a long, narrow gastric pouch is created and anastomosed to the jejunum about 200- 250 cm from the angle of Treitz in an omega loop fashion, thereby avoiding a jejuno-jejunostomy.Proponents of the OLGBP claim that it is a safer and simpler operation than the traditional Roux-en-Y gastric bypass (RYGBP), easier to teach, that gives the same results in terms of weight loss than the RYGBP. One randomized study comparing the two techniques showed similar results after five years.The OLGBP is criticized because it creates an anastomosis between the gastric pouch and the jejunum where a large amount of biliopancreatic juices travel, thereby creating a situation where reflux of the latter into the stomach and distal esophagus is likely to develop. Such a situation has clearly been associated, in several animal studies, with an increased incidence of gastric cancer, especially at or close to the gastro-jejunostomy, and with an increased risk of lower esophageal cancer. In clinical practice, omega-loop gastrojejunostomies such as those used for reconstruction after gastric resection for benign disease or distal gastric cancer have been associated with the so called classical anastomotic cancer, linked to biliary reflux into the stomach, despite the fact that epidemiological studies about this do not show uniform results. Although no evidence at the present time links OLGBP to an increased risk of gastric cancer in the human, this possibility raises a concern among many bariatric surgeons, especially in the view that bariatric surgery is performed in relatively young patients with a long life expectancy, hence prone to develop cancer if indeed the risk is increased. Another arguments used against the OLGBP is that the jejuno-jejunostomy in the traditional RYGBP is easy to perform and associated with virtually no complication.Supporters of the OLGBP claim that the liquid that refluxes into the stomach after their procedure is not pure bile and pancreatic juice, but a combination of those with jejunal secretions, and that the latter is not as harmful. We would urge the proponents of the OLGBP to undertake the necessary animal studies to show that their assumption is indeed true before the procedure is performed widely, possibly leading to the development of hundreds of late gastric or esophageal carcinoma in the bariatric population. In the meantime, we strongly believe that RYGBP should remain the gold standard in gastric bypass surgery for morbid obesity.

Preoperative upper gastrointestinal testing can help predicting long-term outcome after gastric banding for morbid obesity.

BACKGROUND: Gastric banding (GB) is one of the most popular bariatric procedures for morbid obesity. Apart from causing weight loss by alimentary restriction, it can interfere with functions of the esophagus and upper stomach. The aim of this study was to evaluate if the results of extensive preoperative upper GI testing were correlated with long-term outcome and complications after GB. METHODS: Using a prospectively maintained computerized database including all the patients undergoing bariatric operations in both our hospitals, we performed a retrospective analysis of the patients who underwent complete upper gastrointestinal (GI) testing (endoscopy, pH monitoring, and manometry) before GB. RESULTS: One hundred thirty-four patients underwent complete testing before GB. Abnormal pH monitoring (increased total reflux time, increased diurnal reflux time, increased number of reflux episodes) predicted the development of complications and especially pouch dilatation and food intolerance. The mean De Meester score was higher among patients who developed complications than in the remaining ones (25.4 vs 17.7, P=0.03). High lower esophageal sphincter pressure also predicted progressive long-term food intolerance. Endoscopic findings were not predictive of the long-term outcome. CONCLUSIONS: There is some association between the function of the upper digestive tract and long-term complications after gastric banding. Abnormal pH monitoring predicts overall long-term complications, especially food intolerance with or without reflux, and pouch dilatation, and a high lower esophageal sphincter pressure predicts long-term food intolerance. Extended upper gastrointestinal testing with endoscopy, 24-h pH monitoring, and esophageal manometry is probably worthwhile in selecting patients for gastric banding.

Epigenetic alteration of the Wnt inhibitory factor-1 promoter occurs early in the carcinogenesis of Barrett's esophagus.

The role of Wnt antagonists in the carcinogenesis of esophageal adenocarcinoma (EAC) remains unclear. We hypothesized that downregulation of the Wnt inhibitory factor-1 (WIF-1) might be involved in the neoplastic progression of Barrett's esophagus (BE). We analyzed the DNA methylation status of the WIF-1 promoter in normal, preneoplastic, and neoplastic samples from BE patients and in EAC cell lines. We investigated the role of WIF-1 on EAC cell growth and the chemosensitization of the cells to cisplatin. We found that silencing of WIF-1 correlated with promoter hypermethylation. EAC tissue samples showed higher levels of WIF-1 methylation compared to the matched normal epithelium. In addition, we found that WIF-1 hypermethylation was more frequent in BE samples from patients with EAC than in BE samples from patients who had not progressed to EAC. Restoration of WIF-1 in cell lines where WIF-1 was methylation-silenced resulted in growth suppression. Restoration of WIF-1 could sensitize the EAC cells to the chemotherapy drug cisplatin. Our results suggest that silencing of WIF-1 through promoter hypermethylation is an early and common event in the carcinogenesis of BE. Restoring functional WIF-1 might be used as a new targeted therapy for the treatment of this malignancy.

Traitement par radiofréquence de l'oesophage de Barrett [Radiofrequency ablation for Barret's esophagus].

Barrett's esophagus consists of the replacement of normal squamous epithelium by a specialised columnar lined epithelium referred to as intestinal metaplasia in the esophagus. It represents a premalignant lesion. The prevalence of Barrett's esophagus is around 1.6%. Esophageal adenocarcinoma results from the development of dysplasia progressing from low to high grade dysplasia and finally adenocarcinoma. Radiofrequency ablation currently represents the treatment of choice in eradicating Barrett's esophagus with associated dysplasia. The technique is based on the application of a radiofrequency current that enables the destruction of the superficial modified epithelium. This new approach presents a good security profile and, compared to other ablative techniques, shows superior results regarding Barrett's eradication.

Systematic surgical closure of patent foramen ovale in selected patients with cerebrovascular events due to paradoxical embolism. Early results of a preliminary study.

OBJECTIVE: To define therapeutic strategy for management of patients with ischemic stroke due to a high probability of paradoxical embolism through a Patent Foramen Ovale (PFO). METHODS: Since 1988 all consecutive patients with cerebrovascular events and PFO from the Stroke Registry of our population-based primary-care center are prospectively studied and followed. Since 1992, among 118 patients with cryptogenic embolic brain infarct or transient ischemic attack (TIA) and PFO, 32 consecutive patients younger than 60 years who presented at least two of the following criteria were admitted for surgery: history of Valsalva strain before stroke (11); multiple clinical events (13); multiple infarcts on brain Magnetic Resonance Imaging (MRI) (15); atrial septal aneurysm (ASA) (16); large right-to-left shunt (> 50 microbubbles) (12). RESULTS: Operative time 135' +/- 33'. CPB time 34' +/- 14'. Aortic crossclamping time 16' +/- 6'. Post-operative bleeding 485 +/- 170 ml. No homologous blood transfusion required. No neurological, cardiac or renal complications. All patients were followed-up corresponding to a cumulative time of 601 patient-months. This revealed no recurrent vascular events nor silent new brain lesions on brain MRI. Systematic simultaneous contrast Trans Esophageal Echocardiography (TEE)-Trans Cranial Doppler showed a small residual interatrial shunt in two patients. CONCLUSION: Surgical closure of a patent foramen ovale can be accomplished with very low morbidity and reduce efficiently the risk of stroke recurrence. It seems to be the option of choice in selected patients with a higher (> 1.5%/year) risk of stroke recurrence.

Wireless capsule pH monitoring: does it fulfil all expectations?

pH monitoring has been used as a diagnostic tool in gastro-oesophageal reflux disease (GERD) for many years. Recent studies have shown that wireless capsule pH monitoring is better tolerated and interferes less with daily activities as compared to traditional catheter-based pH monitoring. Moreover, prolonged recording time (48 h instead of 24 h) is possible with wireless pH monitoring. The main secondary effect of wireless capsule pH monitoring is induction of thoracic discomfort in 10-65% of the patients, which can vary from mild foreign body sensation to severe chest pain. Sensitivity and specificity of wireless capsule monitoring is comparable to that of traditional pH monitoring. It has not been proven yet that better tolerability and a longer recording time increases the diagnostic yield of wireless capsule monitoring in GERD.

History of cholelithiasis and cancer risk in a network of case-control studies.

Background We analyzed the relationship between cholelithiasis and cancer risk in a network of case-control studies conducted in Italy and Switzerland in 1982-2009. Methods The analyses included 1997 oropharyngeal, 917 esophageal, 999 gastric, 23 small intestinal, 3726 colorectal, 684 liver, 688 pancreatic, 1240 laryngeal, 6447 breast, 1458 endometrial, 2002 ovarian, 1582 prostate, 1125 renal cell, 741 bladder cancers, and 21 284 controls. The odds ratios (ORs) were estimated by multiple logistic regression models. Results The ORs for subjects with history of cholelithiasis compared with those without were significantly elevated for small intestinal (OR = 3.96), prostate (OR = 1.36), and kidney cancers (OR = 1.57). These positive associations were observed ≥10 years after diagnosis of cholelithiasis and were consistent across strata of age, sex, and body mass index. No relation was found with the other selected cancers. A meta-analysis including this and three other studies on the relation of cholelithiasis with small intestinal cancer gave a pooled relative risk of 2.35 [95% confidence interval (CI) 1.82-3.03]. Conclusion In subjects with cholelithiasis, we showed an appreciably increased risk of small intestinal cancer and suggested a moderate increased risk of prostate and kidney cancers. We found no material association with the other cancers considered.

Clinical relevance of L-carnitine-supplemented total parenteral nutrition in postoperative trauma. Metabolic effects of continuous or acute carnitine administration with special reference to fat oxidation and nitrogen utilization.

Carnitine-free total parenteral nutrition (TPN) is claimed to result in a carnitine deficiency with subsequent impairment of fat oxidation. The present study was designed to evaluate the possible benefit of carnitine supplementation on postoperative fat and nitrogen utilization. Sixteen patients undergoing total esophagectomy were evenly randomized and received TPN without or with L-carnitine supplementation (74 mumol.kg-1.d-1) during 11 postoperative days. On day 11, a 4-h infusion of L-carnitine (125 mumol/kg) was performed in both groups. The effect of supplementation was evaluated by indirect calorimetry, N balance, and repeated measurements of plasma lipids and ketone bodies. Irrespective of continuous or acute supplementation, respiratory quotient and fat oxidation were similarly maintained throughout the study in both groups whereas N balance appeared to be more favorable without carnitine. We conclude that carnitine-supplemented TPN does not improve fat oxidation or promote N utilization in the postoperative phase.

The potential impact of new effervescent alendronate formulation on compliance and persistence in osteoporosis treatment.

Osteoporotic fractures are a public health problem and their incidence and subsequent economic and social costs are expected to rise in the next future. Different drugs have been developed to reduce osteoporosis and the risk of osteoporotic fractures, and among them, antiresorptive agents, and in particular oral alendronate, are the most widely utilized. However, one of the most common problems with antiresorptive drugs is poor adherence to treatment, which is associated with a high fracture incidence and with an increase in hospitalization costs. One of the main reasons of poor adherence to these treatments is the occurrence of adverse events, mainly at gastrointestinal (GI) level, including dyspepsia, dysphagia, and esophageal ulcers. In light of these considerations the aim of this paper is to perform a literature review to show the pathophysiologic bases of GI alendronate-induced adverse events and how new bisphosphonate formulations like effervescent alendronate can improve compliance and persistence to treatment and decrease the fracture rate incidence in osteoporotic patients.

Incidence, prevalence and clinical significance of abnormal hematological indices in compensated cirrhosis.

Background & Aims: Patients with cirrhosis develop abnormal hematologic indices (HI) from multiple factors, including hypersplenism. We aimed to analyze the sequence of events and determine whether abnormal HI has prog-nostic significance. Methods: We analyzed a database of 213 subjects with compensated cirrhosis without esopha-geal varices. Subjects were followed for approximately 9 years until the development of varices or variceal bleeding or completion of the study; 84 subjects developed varices. Abnormal HI was defined as anemia at baseline (hemoglo-bin,<13.5 g/dL for men and 11.5 g/dL for women), leuko-penia (white blood cell counts,<4000/mm 3 ), or thrombo-cytopenia (platelet counts, < 150,000/mm 3 ). The primary end points were death or transplant surgery. Results: Most subjects had thrombocytopenia at baseline. Kaplan-Meier analysis showed that leukopenia occurred by 30 months (95% confidence interval, 18.5-53.6), and anemia occurred by 39.6 months (95% confidence interval, 24.1-49.9). Baseline thrombocytopenia (P .0191) and leukope-nia (P.0383) were predictors of death or transplant, after adjusting for baseline hepatic venous pressure gradient (HVPG), and Child-Pugh scores. After a median of 5 years,a significant difference in death or transplant, mortality,and clinical decompensation was observed in patients who had leukopenia combined with thrombocytopenia at base- line compared with patients with normal HI (P < .0001). HVPG correlated with hemoglobin and white blood cell count (hemoglobin, r 0.35, P < .0001; white blood cell count, r 0.31, P < .0001). Conclusions: Thrombocy-topenia is the most common and first abnormal HI to occurin patients with cirrhosis, followed by leukopenia and anemia. A combination of leukopenia and thrombocytopenia at baselin predicted increased morbidity and mortality.

Non-invasive diagnostic and prognostic evaluation of liver cirrhosis and portal hypertension.

Cirrhosis is the final stage of most of chronic liver diseases, and is almost invariably complicated by portal hypertension, which is the most important cause of morbidity and mortality in these patients. This review will focus on the non-invasive methods currently used in clinical practice for diagnosing liver cirrhosis and portal hypertension. The first-line techniques include physical examination, laboratory parameters, transient elastography and Doppler-US. More sophisticated imaging methods which are less commonly employed are CT scan and MRI, and new technologies which are currently under evaluation are MR elastography and acoustic radiation force imaging (ARFI). Even if none of them can replace the invasive measurement of hepatic venous pressure gradient and the endoscopic screening of gastroesophageal varices, they notably facilitate the clinical management of patients with cirrhosis and portal hypertension, and provide valuable prognostic information.