Stress ulcer prophylaxis in non-critically ill patients: a prospective evaluation of current practice in a general surgery department.

RATIONALE, AIMS AND OBJECTIVES: There is little evidence regarding the benefit of stress ulcer prophylaxis (SUP) outside a critical care setting. Overprescription of SUP is not devoid of risks. This prospective study aimed to evaluate the use of proton pump inhibitors (PPIs) for SUP in a general surgery department. METHOD: Data collection was performed prospectively during an 8-week period on patients hospitalized in a general surgery department (58 beds) by pharmacists. Patients with a PPI prescription for the treatment of ulcers, gastro-oesophageal reflux disease, oesophagitis or epigastric pain were excluded. Patients admitted twice during the study period were not reincluded. The American Society of Health-System Pharmacists guidelines on SUP were used to assess the appropriateness of de novo PPI prescriptions. RESULTS: Among 255 patients in the study, 138 (54%) received a prophylaxis with PPI, of which 86 (62%) were de novo PPI prescriptions. A total of 129 patients (94%) received esomeprazole (according to the hospital drug policy). The most frequent dosage was at 40 mg once daily. Use of PPI for SUP was evaluated in 67 patients. A total of 53 patients (79%) had no risk factors for SUP. Twelve and two patients had one or two risk factors, respectively. At discharge, PPI prophylaxis was continued in 33% of patients with a de novo PPI prescription. CONCLUSIONS: This study highlights the overuse of PPIs in non-intensive care unit patients and the inappropriate continuation of PPI prescriptions at discharge. Treatment recommendations for SUP are needed to restrict PPI use for justified indications.

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.

Epigenetic alterations and constitutive Wnt signaling are early events in the progression from Barrett's esophagus to esophageal adenocarcinoma

SUMMARY Barrett's esophagus (BE) is an acquired condition in which the normal squamous epithelium in the distal esophagus is replaced by a metaplastic columnar epithelium, as a complication of chronic gastroesophageal reflux. The clinical significance of this disease is its associated predisposition to esophageal adenocarcinoma (EAC). EAC is a highly lethal disease. Better understanding of the pathogenesis of columnar metaplasia and its progression to cancer might allow the identification of biomarkers that can be used for early diagnosis, which will improve the patient survival. In this study, an improved protocol for methylation-sensitive single-strand conformation analysis, which is used to analyze promoter methylation, is proposed and a methylation-sensitive dot blot assay is described, which allows a rapid, easy, and sensitive detection of promoter methylation. Both methods were applied to study the methylation pattern of the APC promoter in histologically normal appearing gastric mucosa. The APC promoter showed monoallelic methylation, and because the methylated allele differed between the different gastric cell types, this corresponded to allelic exclusion. The APC methylation pattern was frequently altered in noimal gastric mucosa associated with neoplastic lesions, indicating that changes in the pattern of promoter methylation might precede the development of neoplasia, without accompanying histological manifestations. An epigenetic profile of 10 genes important in EAC was obtained in this study; 5 promoter genes (APC, TIMP3, TERT, CDKN2A and SFRP1) were found to be hypermethylated in the tumors. Furthermore, the promoter of APC, TIMP3 and TERT was frequently methylated in BE samples from EAC patients, but rarely in BE samples that did not progress to EAC. These three biomarkers might therefore be considered as potential predictive markers for increased EAC risk. Analysis of Wnt pathway alterations indicated that WNT2 ligand is overexpressed as early as the low-grade dysplastic stage and downregulation by promoter methylation of the SFRP1 gene occurrs already in the metaplastic lesions. Moreover, loss of APC expression is not the only factor involved in the activation of the Wnt pathway. These results indicate that a variety of biologic, mostly epigenetic events occurs very early in the carcinogenesis of BE. This new information might lead to improved early diagnosis of EAC and thus open the way to a possible application of these biomarkers in the prediction of increased EAC risk progression. RESUME L'oesophage de Barrett est une lésion métaplasique définie par le remplacement de la muqueuse malpighienne du bas oesophage par une muqueuse cylindrique glandulaire, suite à une agression chronique par du reflux gastro-esophagien. La plus importante signification clinique de cette maladie est sa prédisposition au développement d'un adénocarcinome. Le pronostic de l'adénocarcinome sur oesophage de Barrett est sombre. Seule une meilleure compréhension de la pathogenèse de l'épithélium métaplasique et de sa progression néoplasique permettrait l'identification de biomarqueurs pouvant être utilisés pour un diagnostic précoce ; la survie du patient serait ainsi augmentée. Dans cette étude, un protocole amélioré pour l'analyse de la méthylation par conformation simple brin est proposé. De plus, une technique d'analyse par dot blot permettant une détection rapide, facile et sensible de la méthylation d'un promoteur est décrite. Les deux méthodes ont été appliquées à l'étude de la méthylation du promoteur du gène APC dans des muqueuses gastriques histologiquement normales. Le promoteur APC a montré une méthylation monoallélique et, parce que les allèles méthylés différaient entre les différents types de cellules gastriques, celle-ci correspondait à une méthylation allélique exclusive. La méthylation d'APC a été trouvée fréquemment altérée dans la muqueuse gastrique normale associée à des lésions néoplasiques. Ceci indique que des changements dans la méthylation d'un promoteur peuvent précéder le développement d'une tumeur, et cela sans modification histologique. Un profil épigénétique des adénocarcinomes sur oesophage de Barrett a été obtenu dans cette étude. Cinq promoteurs (APC, TIMP3, TERT, CDKN2A et SFRP1) ont été trouvés hyperméthylés dans les tumeurs. Les promoteurs d'APC, TIMP3 et TERT étaient fréquemment méthylés dans l'épithélium métaplasique proche d'un adénocarcinome et rarement dans l'épithélium sans évolution néoplasique. Ces trois biomarkers pourraient par conséquent être considérés comme marqueur prédicatif d'un risque accru de développer une tumeur. L'analyse des altérations de la voie Wnt a montré que WNT2 est surexprimé déjà dans des dysplasies de bas-grade et que la dérégulation de SFRP1 par méthylation de son promoteur intervenait dans les lésions métaplasiques. Une perte d'expression d'APC n'est pas le seul facteur impliqué dans l'activation de cette voie. Ces résultats montrent qu'une grande diversité d'événements biologiques, principalement épigénétiques, surviennent très tôt lors de la carcinogenèse de l'oesophage de Barrett. Ces nouveaux éléments pourraient améliorer le diagnostic précoce et rendre possible l'application de ces biomarqueurs dans la prédiction d'un risque accru de développer un adénocarcinome sur un oesophage de Barrett.

Gastrostomies endoscopiques percutanées chez l'enfant

RESUME Une gastrostomie est un montage chirurgical d'ouverture d'un orifice cutané donnant un accès direct à l'estomac pour permettre l'alimentation et la décompression gastrique. La gastrostomie est indiquée au cours de certaines maladies chroniques de patients ayant un tube digestif fonctionnel. La gastrostomie percutanée par endoscopie (Percutaneous Endoscopie Gastrostomy PEG) a été décrite en 1977 par Michael W. Gauderer. La méthode est sûre et rapide. Peuvent en bénéficier les patients très affaiblis par leur maladie, pour lesquels une longue anesthésie est à éviter. La réalisation d'une PEG nécessite la collaboration d'un chirurgien, d'un gastro- entérologue et d'un anesthésiste, tous trois spécialisés en pédiatrie. La partie théorique de cette thèse est consacrée à l'historique des gastrostomies et aux diverses techniques de nutrition entérale. La partie pratique de la PEG est étudiée avec ses variantes, ses indications, contre-indications et complications. Cette partie pratique est basée sur 12 ans d'expérience du Service de Chirurgie Pédiatrique du CHUV. Il s'agit d'une étude rétrospective de dossiers, associée à un questionnaire adressé aux patients en mars 2000. 55 PEG ont été posées selon la technique de Gauderer entre 1989 et 2000. Les indications sont les maladies oncologiques (13), neurologiques (13), la mucoviscidose (12), les maladies métaboliques (6) et d'autres indications variées (11). Le bénéfice nutritionnel est étudié pour chaque type d'indications par l'évolution du gain pondéral après la PEG. Les problèmes rencontrés sont principalement des complications mineures de type inflammation de l'orifice. Nous avons observé 2 complications majeures, en ce que leurs conséquences auraient pu être graves. Le respect strict des contre-indications est nécessaire : 3 cas ont été récusés pour raison de sécurité. Le reflux gastro-oesophagien reste une affection concomitante, principalement chez les patients dont la maladie de base est d'origine neurologique. La qualité de vie de l'enfant et de sa famille est investiguée par des questions précises combinées à des plages de commentaires. Nous avons ainsi évalué le degré de satisfaction des enfants et de leur entourage. En conclusion la gastrostomie endoscopique percutanée est une opération simple, rapide et sûre, susceptible d'apporter un gain pondéral. Son utilisation pourrait être plus répandue. Elle apporte aussi une meilleure qualité de vie aux enfants qui en bénéficient, avec une amélioration de leurs performances et une diminution des conflits associés à des repas laborieux.

Fungus ball in the urinary tract: A rare entity.

A fungal mass in the urinary tract (fungus ball), mainly occurring in compromised patients, is a rare and dangerous complication of candiduria. We report 2 cases of fungus ball associated with hydronephrosis and sepsis. As reported in the literature, we treated the first patient by prompt relief of obstruction by nephrostomy and local and systemic antifungal agent. The second patient failed to respond to this treatment due to a distal ureteral stenosis and required open surgery with fungus ball removal and ureteral reimplantation. Despite a large success in urinary tract drainage with antifungal treatments, some cases need a modified approach due to anatomical modification.

O valor da tomografia computadorizada helicoidal sem contraste na avaliação de pacientes com dor no flanco

Os nossos objetivos foram estabelecer a eficácia da tomografia computadorizada sem contraste em diagnosticar a ureterolitíase, calcular a freqüência dos principais sinais tomográficos e medir a concordância interobservador, comparando-a com os resultados obtidos na urografia excretora, realizando estudo prospectivo duplo-cego em 25 pacientes com cólica nefrética. Em ambos os procedimentos avaliamos a existência de aumento renal, hidronefrose e cálculo ureteral. Deste último, descrevemos a sua localização e dimensão. Nos exames de tomografia computadorizada sem contraste procuramos também por estrias perirrenais, edema periureteral e o sinal do halo. Em 23 dos 25 exames de tomografia computadorizada sem contraste (92%) e em 17 das 25 urografias excretoras (68%) houve concordância dos resultados entre os dois observadores. Em 21 dos 25 pacientes os resultados dos dois métodos foram concordantes. Concluímos que a tomografia computadorizada sem contraste apresenta eficácia superponível à urografia excretora na avaliação de pacientes com cólica nefrética, sendo um método reprodutível e sem promover o desconforto do uso do contraste endovenoso.

Tumor de pequenas células redondas desmoplásico intra-abdominal: relato de caso

Os autores relatam um caso de tumor de pequenas células redondas desmoplásico intra-abdominal acometendo paciente do sexo masculino, de 21 anos de idade, atendido com quadro de dor abdominal, trombose do membro inferior direito e perda da função renal, de causa obstrutiva. A investigação demonstrou volumosa lesão abdominopélvica, sólida, bocelada, com áreas císticas internas, situada posteriormente à bexiga, causando obstrução ureteral, compressão da veia ilíaca direita e oclusão parcial do reto, além de acometimento de linfonodos intra e retroperitoneais. São descritos os achados cirúrgicos, de ultra-sonografia, tomografia computadorizada e ressonância magnética, bem como aqueles do estudo macroscópico, microscopia e imuno-histoquímica.

Incidence and Risk Factors of Abdominal Complications After Lung Transplantation.

BACKGROUND: Due to the underlying diseases and the need for immunosuppression, patients after lung transplantation are particularly at risk for gastrointestinal (GI) complications that may negatively influence long-term outcome. The present study assessed the incidences and impact of GI complications after lung transplantation and aimed to identify risk factors. METHODS: Retrospective analysis of all 227 consecutively performed single- and double-lung transplantations at the University hospitals of Lausanne and Geneva was performed between January 1993 and December 2010. Logistic regressions were used to test the effect of potentially influencing variables on the binary outcomes overall, severe, and surgery-requiring complications, followed by a multiple logistic regression model. RESULTS: Final analysis included 205 patients for the purpose of the present study, and 22 patients were excluded due to re-transplantation, multiorgan transplantation, or incomplete datasets. GI complications were observed in 127 patients (62 %). Gastro-esophageal reflux disease was the most commonly observed complication (22.9 %), followed by inflammatory or infectious colitis (20.5 %) and gastroparesis (10.7 %). Major GI complications (Dindo/Clavien III-V) were observed in 83 (40.5 %) patients and were fatal in 4 patients (2.0 %). Multivariate analysis identified double-lung transplantation (p = 0.012) and early (1993-1998) transplantation period (p = 0.008) as independent risk factors for developing major GI complications. Forty-three (21 %) patients required surgery such as colectomy, cholecystectomy, and fundoplication in 6.8, 6.3, and 3.9 % of the patients, respectively. Multivariate analysis identified Charlson comorbidity index of ≥3 as an independent risk factor for developing GI complications requiring surgery (p = 0.015). CONCLUSION: GI complications after lung transplantation are common. Outcome was rather encouraging in the setting of our transplant center.

Sinais de uretelolitíase na tomografia computadorizada helicoidal sem contraste: ensaio iconográfico e revisão de literatura

O principal sinal diagnóstico de ureterolitíase na tomografia computadorizada é a visualização direta do cálculo no interior do ureter. Todavia, a sua caracterização pode ser prejudicada devido a suas pequenas dimensões, variação da respiração entre a aquisição dos cortes tomográficos, escassez de gordura retroperitoneal ou eliminação recente do cálculo. Neste contexto, foram descritos diversos sinais secundários de obstrução ureteral, observados na tomografia computadorizada, que podem auxiliar no diagnóstico de casos duvidosos, além de quantificar o grau de obstrução urinária.

Avaliação da concordância interobservador na análise da tomografia computadorizada sem contraste no diagnóstico da urolitíase em pacientes com cólica renal aguda

OBJETIVO: Avaliar a reprodutibilidade da tomografia computadorizada sem contraste na avaliação da litíase ureteral e os sinais secundários de obstrução do sistema coletor em pacientes com cólica renal aguda. MATERIAIS E MÉTODOS: Estudo prospectivo de 52 pacientes com diagnóstico clínico de cólica renal aguda submetidos a exame de tomografia computadorizada de abdome sem contraste. Os exames foram realizados com técnica helicoidal e posteriormente analisados por três observadores independentes, com a concordância interobservador avaliada pelo método estatístico kappa (kapa). Foram analisados os parâmetros: a) presença, localização e mensuração dos cálculos ureterais; b) dilatação do sistema coletor intra-renal; c) heterogeneidade da gordura perirrenal; d) dilatação ureteral; e) edema da parede ureteral (sinal do halo). RESULTADOS: Foram encontrados 40 cálculos ureterais na tomografia computadorizada (77%). A concordância interobservador para a identificação do cálculo ureteral e da dilatação ureteral foi quase perfeita (kapa = 0,89 e kapa = 0,87, respectivamente), substancial para dilatação do sistema coletor intra-renal (kapa = 0,77) e moderada para heterogeneidade da gordura perirrenal e para edema da parede ureteral (kapa = 0,55 e kapa = 0,56, respectivamente). CONCLUSÃO: A tomografia computadorizada de abdome sem contraste apresenta elevada reprodutibilidade na avaliação da litíase ureteral e dos sinais secundários de obstrução do sistema coletor.

Definição do nível da junção ureterovesical pela tomografia computadorizada

OBJETIVO: Definir o nível da implantação ureteral na bexiga através da tomografia computadorizada. MATERIAIS E MÉTODOS: Através de tomografia computadorizada da pelve com contraste endovenoso de 46 pacientes (31 homens e 15 mulheres) com idade entre 18 e 45 anos, com pelo menos um dos ureteres contrastado pelo contraste excretado, medimos as distâncias do meato ureteral até o teto acetabular e a borda superior da sínfise púbica, além do volume da bexiga. Utilizamos o teste t de Student para avaliar se houve diferenças estatísticas entre grupos. RESULTADOS: O nível da implantação ureteral na bexiga foi, em média, 10,6 ± 8,1 mm abaixo do teto acetabular e, em média, 29,7 ± 9,5 mm acima da borda superior da sínfise púbica. Nos pacientes com volume de repleção vesical menor que 200 ml e maior ou igual a 200 ml os níveis da implantação ureteral na bexiga foram, em média, 11,6 ± 7,3 mm e 10,2 ± 8,4 mm abaixo do teto acetabular (p = 0,61) e, em média, 28,3 ± 7,3 mm e 30,3 ± 10,2 mm acima da borda superior da sínfise púbica (p = 0,52), respectivamente, e nos pacientes do sexo masculino e feminino foram, em média, 11,8 ± 8,0 mm e 8,3 ± 8,0 mm abaixo do teto acetabular (p = 0,17) e, em média, 27,7 ± 9,2 mm e 33,9 ± 8,8 mm acima da borda superior da sínfise púbica (p = 0,34), respectivamente. CONCLUSÃO: Calcificações localizadas abaixo de 3 cm do teto acetabular e abaixo de 1,5 cm acima da borda superior da sínfise púbica provavelmente não representam cálculos ureterais. O grau de repleção vesical e o sexo não interferem significativamente na posição do meato ureteral.

Estudo do jato urinário intravesical com Doppler colorido em pacientes com e sem refluxo vesicoureteral

OBJETIVO: O presente estudo teve como objetivo comparar os achados da uretrocistografia miccional com o ultra-som Doppler duplex colorido, em pacientes com suspeita de refluxo vesicoureteral. MATERIAIS E MÉTODOS: A pesquisa foi realizada através do estudo dos ângulos dos jatos urinários intravesicais, nos planos axial e longitudinal. Foi analisada, também, a distância (em centímetros) entre os meatos ureterais. RESULTADOS: Do total de 32 pacientes estudados (com média de idade de 5 anos e 2 meses), 18 pacientes apresentaram refluxo vesicoureteral (10 com refluxo unilateral, sendo 4 no lado direito e 6 no lado esquerdo, e 8 com refluxo bilateral) e 14 pacientes não apresentaram refluxo. Os valores angulares dos jatos urinários intravesicais e as distâncias entre os meatos ureterais foram obtidos para todos os pacientes e foram calculados a média, o desvio-padrão e o coeficiente de variação. CONCLUSÃO: Os dados evidenciaram tendência de que a lateralização do meato ureteral seja sinal de predisposição ao refluxo vesicoureteral. A análise estatística não-paramétrica de Mann-Whitney não evidenciou diferenças significativas (p > 0,05) entre os grupos (ângulos de inclinação dos jatos urinários intravesicais e distância entre os meatos ureterais).

The nitric oxide pathway in pig isolated calyceal smooth muscle.

In pig and humans, whose kidneys have a multi-calyceal collecting system, the initiation of ureteral peristalsis takes place in the renal calyces. In the pig and human ureter, recent evidence suggests that nitric oxide (NO) is an inhibitory mediator that may be involved in the regulation of peristalsis. This study was designed to assess whether the NO synthase/NO/cyclic GMP pathway modulates the motility of pig isolated calyceal smooth muscle. Immunohistochemistry revealed a moderate overall innervation of the smooth muscle layer, and no neuronal or inducible NO synthase (NOS) immunoreactivities. Endothelial NOS immunoreactivities were observed in the urothelium and vascular endothelium, and numerous cyclic GMP-immunoreactive (-IR) calyceal smooth muscle cells were found. As measured by monitoring the conversion of L-arginine to L-citrulline, Ca(2+)-dependent NOS activity was moderate. Assessment of functional effects was performed in tissue baths and showed that NO and SIN-1 decreased spontaneous and induced contractions of isolated preparations in a concentration-dependent manner. In strips exposed to NO, there was a 10-fold increase of the cyclic GMP levels compared with control preparations (P < 0.01). It is concluded that a non-neuronal NOS/NO/cyclic GMP pathway is present in pig calyces, where it may influence motility. The demonstration of cyclic GMP-IR smooth muscle cells suggests that NO acts directly on these cells. This NOS/NO/cyclic GMP pathway may be a target for drugs inhibiting peristalsis of mammalian upper urinary tract. Neurourol. Urodynam. 18:673-685, 1999.

Traitements chirurgicaux des maladies fonctionnelles oesogastriques [Surgical treatment of gastroesophageal diseases].

Les pathologies fonctionnelles oesogastriques regroupent plusieurs maladies touchant la fonction digestive haute : la maladie de reflux, les hernies hiatales, l'oesophage court et l'achalasie. Leur mode de présentation est parfois similaire, mais leur traitement diffère sur de nombreux points. L'approche initiale passe souvent par une modification de l'hygiène de vie et une prise en charge médicale. Mais une prise en charge chirurgicale est parfois nécessaire. Une sélection très stricte des patients permet de garantir un bon résultat à long terme, tout en limitant le risque de complications. Elle repose sur un bilan fonctionnel précis et une prise en charge dans le cadre de discussions multidisciplinaires. Cette revue fait un point actuel sur la prise en charge générale, les bilans nécessaires et les traitements chirurgicaux disponibles. Gastroesophageal functional diseases comprise several pathologies impending upper gastrointestinal function: reflux disease, hiatal hernias, short esophagus and achalasia. Their presentation may be similar, but their treatment differs on many points. The initial approach consists of lifestyle changes and medical management. However, surgical treatment is sometimes necessary. Strict patient selection ensures good long-term results, while limiting the risk of complications. This selection is based on precise functional assessment and management in the context of multidisciplinary discussions. This article aims to discuss current aspects on general management, functional investigations and surgical treatments available.

Diagnostic approach to eosinophilic oesophagitis: Pearls and pitfalls.

Eosinophilic oesophagitis (EoE) has first been described a little over 20 years ago. EoE has been defined by a panel of international experts as a "chronic, immune/antigen-mediated, oesophageal disease, characterized clinically by symptoms related to oesophageal dysfunction and histologically by eosinophil-predominant inflammation". A value of ≥ 15 eosinophils has been defined as histologic diagnostic cutoff. Other conditions associated with oesophageal eosinophilia, such as gastro-oesophageal reflux disease (GERD), PPI-responsive oesophageal eosinophilia, or Crohn's disease should be excluded before EoE can be diagnosed. This review highlights the latest insights regarding the diagnosis and differential diagnosis of EoE.