Necrosis esofágica aguda (esófago negro) asociado a neoplasias digestivas / Acute esophageal necrosis (black esophagus) associated with digestive neoplasms

INTRODUCCIÓN. La necrosis esofágica aguda es un síndrome raro que se caracteriza endoscópicamente por una apariencia negra circunferencial irregular o difusa de la mucosa esofágica intratorácica, la afectación es generalmente del esófago distal y la transición abrupta de mucosa normal en la unión gastroesofágica, con extensión proximal variable. CASOS. Se presentan dos casos con diferentes comorbiliades, presentación de signos y síntomas, antecedentes y tratamiento, teniendo en común el diagnóstico a través de endoscopía digestiva alta. RESULTADOS. Caso clínico 1: tratamiento clínico basado en hidratación, suspensión de vía oral, omeprazol intravenoso y sucralfato; mala evolución clínica caracterizada por: disfagia, intolerancia oral y recurrencia del sangrado digestivo alto, se realiza colocación de gastrostomía endoscópica. Caso clínico 2: esófago con mucosa con fibrina y parches de necrosis extensa, se realiza compensación tanto de foco infeccioso pulmonar como hidratación y nutrición, en estudios complementarios se observa masa colónica, con estudio histopatológico confirmatorio de adenocarcinoma de colon en estado avanzado. DISCUSIÓN. La esofagitis necrotizante aguda es una entidad inusual, de baja prevalencia e incidencia, asociada con estados de hipoperfusión sistémica y múltiples comorbilidades que favorezcan un sustrato isquémico. Al revisar los reportes de casos que hay en la literatura médica, los casos que reportamos se correlaciona con las características clínicas, epidemiológicas, endoscópicas y factores de riesgo causales de la enfermedad. La presentación clínica más frecuente es el sangrado digestivo alto, que se debe correlacionar con el hallazgo endoscópico clásico. Nuestro primer caso reportado termina con la colocación de una gastrostomía para poder alimentarse. CONCLUSIÓN. El pronóstico de la necrosis esofágica aguda es malo y se requiere un alto índice de sospecha clínica y conocimiento de esta infrecuente patología para un diagnóstico temprano y un manejo oportuno. Se requiere una evaluación por endoscopia digestiva alta. Es una causa de sangrado gastrointestinal que conlleva tasas altas de mortalidad, principalmente en adultos mayores frágiles. El reconocimiento temprano y la reanimación agresiva son los principios fundamentales para un mejor resultado de la enfermedad.

INTRODUCTION. Acute esophageal necrosis is a rare syndrome that is characterized endoscopically by an irregular or diffuse circumferential black appearance of the intrathoracic esophageal mucosa, the involvement is generally of the distal esophagus and the abrupt transition of normal mucosa at the gastroesophageal junction, with variable proximal extension. CASES. Two cases are presented with different comorbidities, presentation of signs and symptoms, history and treatment, having in common the diagnosis through upper gastrointestinal endoscopy. RESULTS. Clinical case 1: clinical treatment based on hydration, oral suspension, intravenous omeprazole and sucralfate; poor clinical evolution characterized by: dysphagia, oral intolerance and recurrence of upper digestive bleeding, endoscopic gastrostomy placement was performed. Clinical case 2: esophagus with mucosa with fibrin and patches of extensive necrosis, compensation of both the pulmonary infectious focus and hydration and nutrition is performed, in complementary studies a colonic mass is observed, with a confirmatory histopathological study of colon adenocarcinoma in an advanced state. DISCUSSION. Acute necrotizing esophagitis is an unusual entity, with low prevalence and incidence, associated with states of systemic hypoperfusion and multiple comorbidities that favor an ischemic substrate. When reviewing the case reports in the medical literature, the cases we report correlate with the clinical, epidemiological, endoscopic characteristics and causal risk factors of the disease. The most common clinical presentation is upper gastrointestinal bleeding, which must be correlated with the classic endoscopic finding. Our first reported case ends with the placement of a gastrostomy to be able to feed. CONCLUSION. The prognosis of acute esophageal necrosis is poor and a high index of clinical suspicion and knowledge of this rare pathology is required for early diagnosis and timely management. Evaluation by upper gastrointestinal endoscopy is required. It is a cause of gastrointestinal bleeding that carries high mortality rates, mainly in frail older adults. Early recognition and aggressive resuscitation are the fundamental principles for a better outcome of the disease.

Esophageal ulcer related to zinc deficiency following a total gastrectomy.

A 76-y-old Japanese man who had undergone gastrectomy 4.5 y earlier experienced 2 wk of sore throat, heartburn, and difficulty swallowing. Endoscopy showed deep, craterlike, longitudinal ulcers in the lower and middle esophagus. Immunohistochemistry and blood tests were negative for herpes simplex virus and cytomegalovirus infections. The patient reported no other symptoms affecting the gastrointestinal tract. Although his symptoms ameliorated after initial hospitalization and treatment, they re-emerged a few days after being discharged. Fifty-one days after being first admitted, he complained of glossalgia. The serum zinc level was found to be 38 µg/dL, which was below the reference range; the patient was diagnosed with zinc deficiency. After oral zinc administration, the patient was relieved of the symptoms, and his pain was alleviated. Upper gastrointestinal endoscopy after symptom relief showed improvement in the esophageal ulcers. He has continued taking zinc supplementations, and has not developed similar symptoms in the 5 y since being treated. To the best of our knowledge, this is the first case report of esophageal ulcers related to zinc deficiency.

Effect of Delayed Endoscopy Protocol on Timing and Safety of Endoscopy for Foreign Body Ingestion and Esophageal Food Impaction.

BACKGROUND AND AIMS: Endoscopic procedures for foreign body ingestion (FBI) and esophageal food impactions (EFI) performed during on-call hours are associated with increased stress, risk, and cost. We implemented a Foreign Body Algorithm (FBA) designed to delay all but the most urgent endoscopy for EFI and FBI until regular working hours. METHODS: Using endoscopy records from multiple academic and community hospitals within a large integrated health system in the United states, we identified esophagogastroduodenoscopy (EGD) performed for food impactions and foreign body ingestions occurring between May 2011 and February 2021. RESULTS: We identified 479 EGDs performed for FBI and EFI. The introduction of the FBA was associated with a shorter length of stay (LOS) for overall cases (0.35 vs. 0.8 d P <0.001), day cases (0.16 vs. 1.0 d P <0.001), and night cases (0.40 vs. 0.6 d P =0.03). The introduction of the FBA did not change the rate of overall adverse events (AE) or night AE. AE from the entire cohort was rare (3%; 16 total). Of the AE, most were sedation related. The introduction of the FBA did not affect the overall rate of night cases or AE, but the rate of after-hours endoscopy for intentional ingestions decreased from 17.2% to 3.1% ( P =0.01). CONCLUSION: This is one of the largest studies of esophageal impactions and foreign bodies in adults in the United States, and the first to examine the effects of a protocol designed to avoid after-hours endoscopy. These results suggest that postponing after-hours EGD until the daytime is not associated with adverse safety outcomes or increased LOS.

Role of microbial dysbiosis in the pathogenesis of esophageal mucosal disease: A paradigm shift from acid to bacteria?

Genomic sequencing, bioinformatics, and initial speciation (e.g., relative abundance) of the commensal microbiome have revolutionized the way we think about the "human" body in health and disease. The interactions between the gut bacteria and the immune system of the host play a key role in the pathogenesis of gastrointestinal diseases, including those impacting the esophagus. Although relatively stable, there are a number of factors that may disrupt the delicate balance between the luminal esophageal microbiome (EM) and the host. These changes are thought to be a product of age, diet, antibiotic and other medication use, oral hygiene, smoking, and/or expression of antibiotic products (bacteriocins) by other flora. These effects may lead to persistent dysbiosis which in turn increases the risk of local inflammation, systemic inflammation, and ultimately disease progression. Research has suggested that the etiology of gastroesophageal reflux disease-related esophagitis includes a cytokine-mediated inflammatory component and is, therefore, not merely the result of esophageal mucosal exposure to corrosives (i.e., acid). Emerging evidence also suggests that the EM plays a major role in the pathogenesis of disease by inciting an immunogenic response which ultimately propagates the inflammatory cascade. Here, we discuss the potential role for manipulating the EM as a therapeutic option for treating the root cause of various esophageal disease rather than just providing symptomatic relief (i.e., acid suppression).

Curcumin: A Potent Protectant against Esophageal and Gastric Disorders.

Turmeric obtained from the rhizomes of Curcuma longa has been used in the prevention and treatment of many diseases since the ancient times. Curcumin is the principal polyphenol isolated from turmeric, which exhibits anti-inflammatory, antioxidant, antiapoptotic, antitumor, and antimetastatic activities. The existing evidence indicates that curcumin can exert a wide range of beneficial pleiotropic properties in the gastrointestinal tract, such as protection against reflux esophagitis, Barrett's esophagus, and gastric mucosal damage induced by nonsteroidal anti-inflammatory drugs (NSAIDs) and necrotizing agents. The role of curcumin as an adjuvant in the treatment of a Helicobacter pylori infection in experimental animals and humans has recently been proposed. The evidence that this turmeric derivative inhibits the invasion and proliferation of gastric cancer cells is encouraging and warrants further experimental and clinical studies with newer formulations to support the inclusion of curcumin in cancer therapy regimens. This review was designed to analyze the existing data from in vitro and in vivo animal and human studies in order to highlight the mechanisms of therapeutic efficacy of curcumin in the protection and ulcer healing of the upper gastrointestinal tract, with a major focus on addressing the protection of the esophagus and stomach by this emerging compound.

Oesophageal ulcer due to a herbal remedy.

Herbal-induced oesophageal lesions are rare. We report the case of an 85-year-old male who presented with cough and odynophagia. An upper endoscopy showed white deposit under the proximal oesophageal sphincter. Biopsy of the lesion revealed an oesophageal ulcer with adherent plant material and ruled-out candidiasis. At this point, the patient divulged self-preparation of an herbal remedy consisting of Aloe Vera pulp, whisky, honey, ginger and turmeric. Aloe Vera, ginger and turmeric are commonly used to sooth some gastroenterological symptoms in Complementary and Alternative Medicine. Incorrect extraction of Aloe Vera pulp and adding honey to it transformed the recipe into a sticky paste that may have injured the oesophageal mucosa. Follow-up showed that the cough and odynophagia subsided after discontinuing this herbal remedy.

Non-cardiac chest pain: a 2018 update.

Non-cardiac chest pain (NCCP) is defined as recurring, angina-like, chest pain of non-cardiac origin. Studies have estimated that gastroesophageal reflux disease (GERD) is the most common contributing factor for NCCP. In patients with non-GERD related NCCP, esophageal motility disorders, and functional chest pain of presumed esophageal origin are the main underlying mechanisms for symptoms. Epidemiologic studies show a high prevalence of panic disorder, anxiety and major depression in NCCP patients. The diagnostic esophageal workup starts only after that cardiac and pulmonary diseases have been ruled out. NCCP patients with typical reflux symptoms are more likely to have GERD-related NCCP than those without typical reflux symptoms. High-dose proton pump inhibitor trial (PPI test) can be used to confirm the diagnosis of GERD-related NCCP. Negative upper endoscopy is quite common. For patients unresponsive to antireflux treatment and with negative endoscopy, impedance-pH monitoring should be done. Treatment of patients with non-GERD-related NCCP has focused on esophageal (hypercontractile or spastic) motility disorders and esophageal visceral hypersensitivity. In the first case, several trials using calcium channel blockers, nitrates, anticholinergics, or botulinum toxin injection and recent trials with endoscopic myotomy have been conducted. In case of visceral hypersensitivity, studies found that the amelioration, when compared to placebo, was significant with venlafaxine, sertraline, and imipramine. In this context, also cognitive behavioral therapy has been proposed.

[A Case of Spontaneous Esophageal Rupture That Required Operation during Adjuvant Chemotherapy for Transverse Colon Cancer].

A 75-year-old male underwent adjuvant chemotherapy with tegafur uracil(UFT)plus Leucovorin(LV)after surgery for transverse colon cancer(pT3pN0M0, ly1, v2, pStageⅡ). Although he had diarrhea(Grade 3)and vomiting(Grade 2)from day 15, he continued to take the medicine at his own discretion. He visited a hospital because of acute renal failure from severe dehydration. He went into shock after evacuation, and the computed tomography(CT)finding suggested a diagnosis of spontaneous esophageal rupture at the lower esophagus. We made a diagnosis of intrathoracic perforation of the esophagus by using thoracic drainage. Then, we performed an operation for mediastinal drainage via a transabdominal approach and the lesser omentum. He started ingestion from POD36 and transferred to another hospital on POD85. He had no disease recurrence in our outpatient care. We think that the spontaneous esophageal rupture occurred because of the frequent vomiting caused by the continued chemotherapy despite the severe side effects. Treatments must be selected by considering patients' life background and medical compliance, and common guidance in taking medications must be provided to elderly patients at the start of chemotherapy.

Hiccups. Attitude in Otorhinolaryngology Towards Consulting Patients. A Diagnostic and Therapeutic Approach. / Hipo. Actitud en otorrinolaringología en pacientes que consultan. Aproximación diagnóstica y terapéutica.

INTRODUCTION: Hiccup crises are generally benign and self-limiting, but longer episodes affect quality of life and must be treated. There are recognisable causes that otorhinolaryngologists must know and be aware for diagnosis and therapeutic alternatives. The main expression is a spasmodic glottic noise with characteristic neck alterations. PATIENTS AND METHODS: This was a retrospective study from 1979 with patients suffering persistent or recurrent hiccups. Chronobiology, comorbidity, findings from explorations, therapies and outcomes were noted. Thirty-seven patients were studied (mean age, 45.5±13.5 years; 30 males), with persistent hiccups in 23 (62%). RESULTS: A potential associated aetiology was observed in 24 cases (65%): oesophageal disorders -mainly gastroesophageal reflux- were detected in 14 cases and concomitant oncological disease was found in 8. Only 3 cases were admitted for surgery due to these findings. Therapeutic strategies with metoclopramide were used in 18 subjects, chlorpromazine in 17 and baclofen in 13, while carbamazepine or haloperidol were used in a minority. Phrenic nerve stimulation was employed in 6 patients. Hiccups disappeared in 32 cases. Out of 22 cases for which follow-up was possible, the hiccups recurred in 5 subjects (the subjects requiring new therapies) and 11 patients died. CONCLUSIONS: Chronic hiccup represents a multidisciplinary challenge that includes potential head and neck affection, a diagnostic schedule for ruling out causes, frequent base oesophageal alterations and high incidence of malignant neoplasm. Prokinetic and neuroleptic agents with antidopaminergic and anticholinergic effects are the pillars of its treatment.

Esophageal stenting for benign and malignant disease: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline

This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE), endorsed by the European Society for Radiotherapy and Oncology (ESTRO), the European Society of Digestive Endoscopy (ESDO), and the European Society for Clinical Nutrition and Metabolism (ESPEN). The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was adopted to define the strength of recommendations and the quality of evidence. Main recommendations for malignant disease 1 ESGE recommends placement of partially or fully covered self-expandable metal stents (SEMSs) for palliative treatment of malignant dysphagia over laser therapy, photodynamic therapy, and esophageal bypass (strong recommendation, high quality evidence). 2 For patients with longer life expectancy, ESGE recommends brachytherapy as a valid alternative or in addition to stenting in esophageal cancer patients with malignant dysphagia. Brachytherapy may provide a survival advantage and possibly a better quality of life compared to SEMS placement alone. (Strong recommendation, high quality evidence.) 3 ESGE recommends esophageal SEMS placement as the preferred treatment for sealing malignant tracheoesophageal or bronchoesophageal fistula (strong recommendation, low quality evidence). 4 ESGE does not recommend the use of concurrent external radiotherapy and esophageal stent treatment. SEMS placement is also not recommended as a bridge to surgery or prior to preoperative chemoradiotherapy. It is associated with a high incidence of adverse events and alternative satisfactory options such as placement of a feeding tube are available. (Strong recommendation, low quality evidence.) Main recommendations for benign disease 1 ESGE recommends against the use of self-expandable stents (SEMSs) as first-line therapy for the management of benign esophageal strictures because of the potential for adverse events, the availability of alternative therapies, and costs (strong recommendation, low quality evidence). 2 ESGE suggests consideration of temporary placement of SEMSs as therapy for refractory benign esophageal strictures (weak recommendation, moderate evidence). Stents should usually be removed at a maximum of 3 months (strong recommendation, weak quality evidence). 3 ESGE suggests that fully covered SEMSs be preferred over partially covered SEMSs for the treatment of refractory benign esophageal strictures, because of their lack of embedment and ease of removability (weak recommendation, low quality evidence). 4 For the removal of partially covered esophageal SEMSs that are embedded, ESGE recommends the stent-in-stent technique (strong recommendation, low quality evidence). 5 ESGE recommends that temporary stent placement can be considered for treating esophageal leaks, fistulas, and perforations. The optimal stenting duration remains unclear and should be individualized. (Strong recommendation, low quality evidence.) 6 ESGE recommends placement of a SEMS for the treatment of esophageal variceal bleeding refractory to medical, endoscopic, and/or radiological therapy, or as initial therapy for patients with massive esophageal variceal bleeding (strong recommendation, moderate quality evidence).

Esophageal stenting for benign and malignant disease: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline.

This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE), endorsed by the European Society for Radiotherapy and Oncology (ESTRO), the European Society of Digestive Endoscopy (ESDO), and the European Society for Clinical Nutrition and Metabolism (ESPEN). The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was adopted to define the strength of recommendations and the quality of evidence. Main recommendations for malignant disease 1 ESGE recommends placement of partially or fully covered self-expandable metal stents (SEMSs) for palliative treatment of malignant dysphagia over laser therapy, photodynamic therapy, and esophageal bypass (strong recommendation, high quality evidence). 2 For patients with longer life expectancy, ESGE recommends brachytherapy as a valid alternative or in addition to stenting in esophageal cancer patients with malignant dysphagia. Brachytherapy may provide a survival advantage and possibly a better quality of life compared to SEMS placement alone. (Strong recommendation, high quality evidence.) 3 ESGE recommends esophageal SEMS placement as the preferred treatment for sealing malignant tracheoesophageal or bronchoesophageal fistula (strong recommendation, low quality evidence). 4 ESGE does not recommend the use of concurrent external radiotherapy and esophageal stent treatment. SEMS placement is also not recommended as a bridge to surgery or prior to preoperative chemoradiotherapy. It is associated with a high incidence of adverse events and alternative satisfactory options such as placement of a feeding tube are available. (Strong recommendation, low quality evidence.) Main recommendations for benign disease 1 ESGE recommends against the use of self-expandable stents (SEMSs) as first-line therapy for the management of benign esophageal strictures because of the potential for adverse events, the availability of alternative therapies, and costs (strong recommendation, low quality evidence). 2 ESGE suggests consideration of temporary placement of SEMSs as therapy for refractory benign esophageal strictures (weak recommendation, moderate evidence). Stents should usually be removed at a maximum of 3 months (strong recommendation, weak quality evidence). 3 ESGE suggests that fully covered SEMSs be preferred over partially covered SEMSs for the treatment of refractory benign esophageal strictures, because of their lack of embedment and ease of removability (weak recommendation, low quality evidence). 4 For the removal of partially covered esophageal SEMSs that are embedded, ESGE recommends the stent-in-stent technique (strong recommendation, low quality evidence). 5 ESGE recommends that temporary stent placement can be considered for treating esophageal leaks, fistulas, and perforations. The optimal stenting duration remains unclear and should be individualized. (Strong recommendation, low quality evidence.) 6 ESGE recommends placement of a SEMS for the treatment of esophageal variceal bleeding refractory to medical, endoscopic, and/or radiological therapy, or as initial therapy for patients with massive esophageal variceal bleeding (strong recommendation, moderate quality evidence).

Long-Term Loss of Response in Proton Pump Inhibitor-Responsive Esophageal Eosinophilia Is Uncommon and Influenced by CYP2C19 Genotype and Rhinoconjunctivitis.

OBJECTIVES: Proton pump inhibitor-responsive esophageal eosinophilia (PPI-REE) is diagnosed in at least one-third of patients with suspected eosinophilic esophagitis (EoE). We aimed to evaluate the durability and factors influencing long-term efficacy of PPI therapy. METHODS: Retrospective multicenter cohort study of patients with PPI-REE who had at least 12 months of follow-up. PPI therapy was tapered to the lowest dose, which maintained clinical remission. Primary outcomes were the proportion of patients with loss of histological response (<15 eos/HPF) and predictors of loss of response. CYP2C19 polymorphisms were determined from blood samples in a subset of patients. RESULTS: Seventy-five PPI-REE patients were included (mean follow-up 26 months (12-85)), of whom fifty-five (73%) had sustained histological remission on low-dose PPI therapy. Loss of response was significantly higher in those patients with a CYP2C19 rapid metabolizer genotype (36% vs. 6%, P = 0.01) and with rhinoconjunctivitis (40% vs. 13%, P = 0.007). On the multivariate analysis, a CYP2C19 rapid metabolizer genotype (odds ratio (OR) 12.5; 95% confidence interval (CI): 1.3-115.9) and rhinoconjunctivitis (OR 8.6; 95% CI: 1.5-48.7) were independent predictors of loss of response. Among relapsing patients, eosinophilia was limited to the distal esophagus in 14/20 (70%). Nine of ten relapsers, with distal eosinophilia, all showing a CYP2C19 rapid metabolizer genotype, regained histological remission after PPI dose intensification. CONCLUSIONS: Most PPI-REE patients remain in long-term remission on low-dose PPI therapy. CYP2C19 rapid metabolizer genotypes and rhinoconjunctivitis were independent predictors of loss of response to PPI, but patients frequently responded to PPI dose escalation.

Hypnotherapy for Esophageal Disorders.

Hypnotherapy is an evidence based intervention for the treatment of functional bowel disorders, particularly irritable bowel syndrome. While similar in pathophysiology, less is known about the utility of hypnotherapy in the upper gastrointestinal tract. Esophageal disorders, most of which are functional in nature, cause painful and uncomfortable symptoms that impact patient quality of life and are difficult to treat from a medical perspective. After a thorough medical workup and a failed trial of proton pump inhibitor therapy, options for treatment are significantly limited. While the pathophysiology is likely multifactorial, two critical factors are believed to drive esophageal symptoms--visceral hypersensitivity and symptom hypervigilance. The goal of esophageal directed hypnotherapy is to promote a deep state of relaxation with focused attention allowing the patient to learn to modulate physiological sensations and symptoms that are not easily addressed with conventional medical intervention. Currently, the use of hypnosis is suitable for dysphagia, globus, functional chest pain/non-cardiac chest pain, dyspepsia, and functional heartburn. In this article the authors will provide a rationale for the use of hypnosis in these disorders, presenting the science whenever available, describing their approach with these patients, and sharing a case study representing a successful outcome.

[Changes in Wnt pathway inhibiting factors in nitrosamine-induced esophageal precancerosis lesions and effect of gexia zhuyu decoction].

OBJECTIVE: To discuss the changes in Wnt pathway inhibiting factors in esophageal precancerosis lesions induced by methyl benzyl nitrosamine (MBNA) and the effect of Gexia Zhuyu decoction. METHOD: Wistar rats were subcutaneously injected with MBNA (3.5 mg x kg(-1) for twice per week to establish the model. Since the 1st day after the model establishment, they were orally administered with Gexia Zhuyu decoction (16, 8 mg x kg(-1)). At the 10th week, esophageal tissues were collected to observe the pathological changes of esophageal mucosa, detect SFRP1, sFRP4, Axin1, Axin2 and GSK-3ß mRNA levels.by fluorescent quantitation PCR analysis and ß-catenin protein level by Western blotting. RESULT: Being induced by MBNA, rats in the model group showed slight atypical hyperplasia in the histopathological examination. Compared with the normal group, Gexia Zhuyu decoction dose high and low groups showed no significant pathomorphological and histological changes. The model group showed lower gene transcription levels of esophageal tissues sFRP1, sFRP4, Axin1 and Axin2 (P < 0.05 or P < 0.01) and higher ß-catenin protein expression level (P < 0.01) than the normal control group. The Gexia Zhuyu decoction low dose group showed higher gene transcription levels of esophageal tissues sFRP1, sFRP4, Axin1 and Axin2 (P < 0.05 or P < 0.01) and lower ß-catenin protein expression level (P < 0.01) than the normal control group. CONCLUSION: Up-regulated ß-catenin protein level and down-regulated Wnt pathway could enhance Wnt pathway activity of MBNA-induced esophageal precancerous lesions. Gexia Zhuyu decoction could down-regulate the ß-catenin protein level and up-regulate the transcription level of Wnt pathway inhibiting factors, but could not block MBNA-induced esophageal precancerosis lesions.

Characterization of digestive involvement in patients with chronic T. cruzi infection in Barcelona, Spain.

BACKGROUND: Digestive damage due to Chagas disease (CD) occurs in 15-20% of patients diagnosed as a result of peristaltic dysfunction in some endemic areas. The symptoms of chronic digestive CD are non-specific, and there are numerous confounders. Diagnosis of CD may easily be missed if symptoms are not evaluated by a well trained physician. Regular tests, as barium contrast examinations, probably lack the necessary sensitivity to detect early digestive damage. METHODS: 71 individuals with T. cruzi infection (G1) and 18 without (G2) coming from Latin American countries were analyzed. They were asked for clinical and epidemiological data, changes in dietary habits, and history targeting digestive and cardiac CD symptoms. Serological tests for T. cruzi, barium swallow, barium enema, an urea breath test, and esophageal manometry were requested for all patients. PRINCIPAL FINDINGS: G1 and G2 patients did not show differences in lifestyle and past history. Fifteen (21.1%) of G1 had digestive involvement. Following Rezende criteria, esophagopathy was observed in 8 patients in G1 (11.3%) and in none of those in G2. Manometry disorders were recorded in 34 G1 patients and in six in G2. Isolated hypotensive lower esophageal sphincter (LES) was found in sixteen G1 patients (23.9%) and four G2 patients (28.8%). Achalasia was observed in two G1 patients. Among G1 patients, ineffective esophageal motility was seen in six (five with symptoms), diffuse esophageal spasm in two (one with dysphagia and regurgitation), and nutcracker esophagus in three (all with symptoms). There were six patients with hypertonic upper esophageal sphincter (UES) among G1. Following Ximenes criteria, megacolon was found in ten G1 patients (13.9%), and in none of the G2 patients. CONCLUSIONS: The prevalence of digestive chronic CD in our series was 21.1%. Dysphagia is a non-pathognomonic symptom of CD, but a good marker of early esophageal involvement. Manometry could be a useful diagnostic test in selected cases, mainly in patients with T. cruzi infection and dysphagia in whose situation barium swallow does not evidence alterations. Constipation is a common but non-specific symptom that can be easily managed. Testing for CD is mandatory in a patient from Latin America with constipation or dysphagia, and if diagnosis is confirmed, megacolon and esophageal involvement should be investigated.

Support for the EUCAST and revised CLSI fluconazole clinical breakpoints by Sensititre® YeastOne® for Candida albicans: a prospective observational cohort study.

OBJECTIVES: Species-specific clinical breakpoints (CBPs) for Candida spp. were established following consideration of clinical outcomes in patients with oesophageal candidiasis. We sought to further determine the validity of the current CBPs based on data from a prospective candidaemia study. PATIENTS AND METHODS: All Candida albicans candidaemia episodes in patients enrolled in the Australian Candidaemia Study and who were treated with fluconazole monotherapy were included. Fluconazole MICs were established using Sensititre(®) YeastOne(®). RESULTS: Two hundred and seventeen evaluable episodes were identified, 93.5% of which occurred in adult patients. Fluconazole was commenced within 72 h of blood culture positivity in 96.3% (209/217) of episodes. Fluconazole doses were appropriate in 89.9% (195/217) of episodes and the median duration of therapy was 14 days (IQR 8-21 days) for the whole cohort. The all-cause 30 day mortality was 19.8% (43/217), with 37.2% (16/43) of deaths attributed to candidaemia. Classification and regression tree (CART) analysis identified a fluconazole MIC target of ≥2 mg/L for infection-related mortality and ≥4 mg/L for overall 30 day mortality. Overall mortality was no different in episodes with isolates above or below the identified MIC target, although there was a trend towards significance (P = 0.051). On univariate analysis, infection-related mortality was significantly increased in C. albicans episodes with an MIC ≥2 mg/L compared with those below this MIC target (20.6% versus 4.9%; P = 0.001). This target remained an independent predictor of infection-related mortality (OR 8.2; 95% CI 2.3-29.7; P = 0.001). CONCLUSIONS: We observed a direct relationship between infection-related mortality and rising fluconazole MIC for C. albicans candidaemia; overall, the data support the EUCAST and revised CLSI fluconazole clinical breakpoints.

Changes in Wnt pathway inhibiting factors in nitrosamine-induced esophageal precancerosis lesions and effect of gexia zhuyu decoction / 中国中药杂志

<p><b>OBJECTIVE</b>To discuss the changes in Wnt pathway inhibiting factors in esophageal precancerosis lesions induced by methyl benzyl nitrosamine (MBNA) and the effect of Gexia Zhuyu decoction.</p><p><b>METHOD</b>Wistar rats were subcutaneously injected with MBNA (3.5 mg x kg(-1) for twice per week to establish the model. Since the 1st day after the model establishment, they were orally administered with Gexia Zhuyu decoction (16, 8 mg x kg(-1)). At the 10th week, esophageal tissues were collected to observe the pathological changes of esophageal mucosa, detect SFRP1, sFRP4, Axin1, Axin2 and GSK-3β mRNA levels.by fluorescent quantitation PCR analysis and β-catenin protein level by Western blotting.</p><p><b>RESULT</b>Being induced by MBNA, rats in the model group showed slight atypical hyperplasia in the histopathological examination. Compared with the normal group, Gexia Zhuyu decoction dose high and low groups showed no significant pathomorphological and histological changes. The model group showed lower gene transcription levels of esophageal tissues sFRP1, sFRP4, Axin1 and Axin2 (P < 0.05 or P < 0.01) and higher β-catenin protein expression level (P < 0.01) than the normal control group. The Gexia Zhuyu decoction low dose group showed higher gene transcription levels of esophageal tissues sFRP1, sFRP4, Axin1 and Axin2 (P < 0.05 or P < 0.01) and lower β-catenin protein expression level (P < 0.01) than the normal control group.</p><p><b>CONCLUSION</b>Up-regulated β-catenin protein level and down-regulated Wnt pathway could enhance Wnt pathway activity of MBNA-induced esophageal precancerous lesions. Gexia Zhuyu decoction could down-regulate the β-catenin protein level and up-regulate the transcription level of Wnt pathway inhibiting factors, but could not block MBNA-induced esophageal precancerosis lesions.</p>

Systemic complications of esophageal lichen planus.

Lichen planus is an uncommon inflammatory mucocutaneous disorder affecting the skin and its appendages, as well as oral and genital mucosa. Involvement of the esophageal mucosa is rare and causes significant morbidity, with dysphagia and risk of long-term complications, such as esophageal strictures and stenosis. Esophageal lichen planus is an underreported condition in the spectrum of lichenoid tissue reactions, presenting the risk of systemic manifestations. We describe a patient with severe, long-standing esophageal lichen planus, which had led to marked weight-loss, malnutrition syndrome and chronic respiratory distress due to recurrent aspiration pneumonia. Diagnosis was confirmed by the presence of concomitant muco-cutaneous lesions and characteristic endoscopic and histological findings. Systemic therapy with cyclosporine A and micronutrient supplementation led to rapid clinical improvement. Early diagnosis of esophageal lichen planus as well as effective systemic immunosuppressive treatment is crucial in order to prevent short- and long-term complications.

Luminal esophageal temperature predicts esophageal lesions after second-generation cryoballoon pulmonary vein isolation.

BACKGROUND: The novel second-generation cryoballoon (CB) facilitates pulmonary vein isolation (PVI) by improved surface cooling. The impact of this redesign on collateral damage is unknown. OBJECTIVE: To investigate the incidence of esophageal lesions after PVI using the second-generation CB and the role of luminal esophageal temperature (LET) measurement as a predictor of lesion formation. METHODS: Thirty-two consecutive patients underwent PVI using the second-generation 28 mm CB. Target application time was 2 × 240 seconds. Ninety-two percent of the PVs were isolated after 1 cryoenergy application. Complete PVI was achieved in all patients. LET with 3 thermocouples was continuously measured during cryoenergy application. Freezing was interrupted only if weakening/loss of phrenic nerve function or low LET (<5 °C) was observed. RESULTS: The lowest measured LET was-12 °C (despite cryoapplication interruption). Postprocedural gastroesophagoscopy was performed after 1-3 days in all patients and showed lesions in 6 of 32 (19%) patients. A minimum LET of≤12 °C predicted esophageal lesions with 100% sensitivity and 92% specificity (area under the receiver-operator characteristic curve 0.97; 95% CI 0.93-1.02; P = .001). Persistent phrenic nerve palsy occurred in 2 (6%) patients during ablation at the right inferior pulmonary vein. Repeat gastroesophagoscopy confirmed healing of lesions after 16 ± 14 days. CONCLUSIONS: Second-generation 28 mm CB PVI is associated with significant esophageal cooling, resulting in lesion formation in 19% of the patients. LET measurement accurately predicts lesion formation and may enhance the safety of the novel device.