The 2018 ISDE achalasia guidelines.

Achalasia is a relatively rare primary motor esophageal disorder, characterized by absence of relaxations of the lower esophageal sphincter and of peristalsis along the esophageal body. As a result, patients typically present with dysphagia, regurgitation and occasionally chest pain, pulmonary complication and malnutrition. New diagnostic methodologies and therapeutic techniques have been recently added to the armamentarium for treating achalasia. With the aim to offer clinicians and patients an up-to-date framework for making informed decisions on the management of this disease, the International Society for Diseases of the Esophagus Guidelines proposed and endorsed the Esophageal Achalasia Guidelines (I-GOAL). The guidelines were prepared according the Appraisal of Guidelines for Research and Evaluation (AGREE-REX) tool, accredited for guideline production by NICE UK. A systematic literature search was performed and the quality of evidence and the strength of recommendations were graded according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Given the relative rarity of this disease and the paucity of high-level evidence in the literature, this process was integrated with a three-step process of anonymous voting on each statement (DELPHI). Only statements with an approval rate >80% were accepted in the guidelines. Fifty-one experts from 11 countries and 3 representatives from patient support associations participated to the preparations of the guidelines. These guidelines deal specifically with the following achalasia issues: Diagnostic workup, Definition of the disease, Severity of presentation, Medical treatment, Botulinum Toxin injection, Pneumatic dilatation, POEM, Other endoscopic treatments, Laparoscopic myotomy, Definition of recurrence, Follow up and risk of cancer, Management of end stage achalasia, Treatment options for failure, Achalasia in children, Achalasia secondary to Chagas' disease.

Role of nitrites in the genesis of adenocarcinoma associated with Barrett's esophagus.

BACKGROUND: Barrett's esophagus (BE) is one of the complications of gastroesophageal reflux disease (GERD) and a premalignant condition. It consists of a process of replacement of the squamous epithelium of the esophagus by intestinal columnar epithelium containing goblet cells, known as specialized intestinal metaplasia with goblet cells, and several factors have been related to its pathogenesis. The objective of this study was to evaluate an experimental model of duodenogastroesophageal reflux and the effect of ingestion of sodium nitrite solution on the genesis of adenocarcinoma associated with Barrett's esophagus. MATERIALS AND METHODS: Sixty male Wistar rats were divided into four groups. Twenty were not submitted to surgery and served as controls (10 animals ingesting only water and 10 ingesting water plus a solution of sodium nitrite), while the remaining 40 animals were submitted to side-to-side duodenogastroesophageal anastomosis (20 animals ingesting only water and 20 ingesting water plus the sodium nitrite solution). The Vienna classification for dysplasia and adenocarcinoma was used in the analysis of results. RESULTS: After 42 weeks of observation, Barrett's esophagus was found in 26.3% (5/19) of the animals submitted to surgery that had not ingested nitrites compared to 72.3% (13/18) of the animals in the group submitted to surgery and given nitrites. Six cases of adenocarcinoma (33.3%) were also found in this latter group. Barrett's esophagus was not found in any of the animals that were not submitted to surgery. Categories 2, 3 and 5 of the Vienna classification were only found in the animals submitted to surgery that also received sodium nitrite (66.7%). CONCLUSION: The ingestion of sodium nitrite associated with duodenogastroesophageal reflux plays an important role in the genesis of adenocarcinoma associated with Barrett's esophagus.

Treatment of achalasia: lessons learned with Chagas' disease.

Chagas' disease (CD) is highly prevalent in South America. Brazilian surgeons and gastroenterologists gained valuable experience in the treatment of CD esophagopathy (chagasic achalasia) due to the high number of cases treated. The authors reviewed the lessons learned with the treatment of achalasia by different centers experienced in the treatment of Chagas' disease. Preoperative evaluation, endoscopic treatment (forceful dilatation and botulinum toxin injection), Heller's myotomy, esophagectomy, conservative techniques other than myotomy, and reoperations are discussed in the light of personal experiences and review of International and Brazilian literature. Aspects not frequently adopted by North American and European surgeons are emphasized. The review shows that nonadvanced achalasia is frequently treated by Heller's myotomy. Endoscopic treatment is reserved to limited cases. Treatment for end-stage achalasia is not unanimous. Esophagectomy was a popular treatment in advanced disease; however, the morbidity/mortality associated to the procedure made some authors seek different alternatives, such as Heller's myotomy and cardioplasties. Minimally invasive approach to esophageal resection may change this concept, although few centers perform the procedure routinely.

Polymorphisms of GSTP1 and GSTT1, but not of CYP2A6, CYP2E1 or GSTM1, modify the risk for esophageal cancer in a western population.

Esophageal cancer is among the most common and fatal tumors in the world. Eighty percent of esophageal tumors are esophageal squamous cell carcinoma (ESCC). Brazil is one of the high incidence areas in the West, where tobacco and alcohol consumption have been associated with ESCC. However, polymorphisms in xenobiotic metabolizing genes may also contribute to the risk. Therefore, in this study, we analyzed the risk of ESCC associated with tobacco and alcohol consumption and with polymorphisms of CYP2A6 (CYP2A6*2), CYP2E1 (CYP2E1*5B, CYP2E1*6), GSTP1 (Ile105Val), GSTM1 and GSTT1 null genotypes in 126 cases and 252 age- and gender-matched controls. Data on the amount, length and type of tobacco and alcohol consumed were collected, and DNA was extracted from blood lymphocytes from all individuals. Polymorphisms were analyzed by polymerase chain reaction (PCR)-multiplex (GSTM1 and T1), PCR-Restriction Fragment Length Polymorphism (CYP2E1*5B and *6 and GSTP1 Ile105Val) or allele-specific PCR amplification (CYP2A6*2). Risks were evaluated by multivariate conditional regression analysis. As expected, tobacco [odds ratio (OR) = 6.71, 95% confidence interval (95% CI) 3.08-14.63] and alcohol (OR = 16.98, CI 7.8-36.98) consumption, independently or together (OR = 26.91, CI 13.39-54.05) were risk factors. GSTP1 Ile105Val polymorphism was an independent risk factor (OR = 2.12, CI 1.37-3.29), whereas GSTT1 wild-type was an independent protective factor for ESCC (OR = 0.37, CI 0.16-0.79). There was approximately 80% statistical power to detect both results. There was no risk associated with CYP2A6, CYP2E1 and GSTM1 polymorphisms. In conclusion, this study suggests an opposite role of GSTP1 and GSTT1 polymorphisms for the risk for ESCC.

Arterial tissue and plasma concentration of enzymatic-driven oxysterols are associated with severe peripheral atherosclerotic disease and systemic inflammatory activity.

INTRODUCTION: Cholesterol undergoes oxidation via both enzymatic stress- and free radical-mediated mechanisms, generating a wide range of oxysterols. In contrast to oxidative stress-driven metabolites, enzymatic stress-derived oxysterols are scarcely studied in their association with atherosclerotic disease in humans. METHODS: 24S-hydroxycholesterol (24S-HC), 25-hydroxycholesterol (25-HC), and 27-hydroxycholesterol (27-HC) were assessed in plasma and arteries with atherosclerotic plaques from 10 patients (54-84 years) with severe peripheral artery disease (PAD) as well as arteries free of atherosclerotic plaques from 13 individuals (45-78 years, controls). RESULTS: Plasma 25-HC was higher in PAD individuals than in controls (6.3[2] vs. 3.9[1.9] ng/mgCol; p = 0.004). 24S-HC and 27-HC levels were, respectively, five- and 20-fold higher in the arterial tissue of PAD individuals than in those of the controls (p = 0.016 and p = 0.001). Plasma C-reactive protein correlated with plasma 24-HC (r = 0.51; p = 0.010), 25-HC (r = 0.75; p < 0.001), 27-HC (r = 0.48; p = 0.015), and with tissue 24S-HC (r = 0.4; p = 0.041) and 27-HC (r = 0.46; p = 0.023). CONCLUSION: Arterial intima accumulation of 27-HC and 24S-HC is associated with advanced atherosclerotic disease and systemic inflammatory activity in individuals with severe PAD.

Responses of the upper esophageal sphincter and esophageal body to graded intraluminal distension.

1. The responses of the upper esophageal sphincter (UES) to graded intraluminal distension of the esophagus were examined to determine response thresholds and to define the functional relationship between the sphincter and the esophageal body. 2. Nine normal subjects underwent manometric examination using a multiluminal tube with an attached inflatable balloon located 10 cm below the UES. Sphincter and esophageal motor responses to six balloon inflation volumes (1, 2, 4, 6, 8, and 10 ml) were recorded in each subject. 3. The UES responded to distension by increasing pressure, from a median value of 42.5 mmHg with a threshold distension of 1.0 cm, to 95 mmHg at 2.2 cm. Non-swallow-related, secondary contractile waves were stimulated in the esophageal body proximal to the distension and increased in number as inflation increased. Distal propagation of this secondary activity was inhibited with increasing distension. The amplitude of the primary peristalsis increased significantly to 61.7 mmHg at 2.2 cm. 4. These data demonstrate the normal upper esophageal motor responses to distension and provide a reference for future investigations of patients showing evidence of impaired esophageal clearance and in whom standard manometry may be unhelpful.

Motor responses of the upper esophageal sphincter and body to intraluminal acid.

1. It is known that contraction of the upper esophageal sphincter (UES) and secondary peristalsis protect the airway and clear the esophagus of refluxed gastric contents. However, the exact nature of the stimulus and the role of acid remain controversial. 2. Secondary peristalsis and UES responses were measured following the intraluminal infusion of 0.1 N hydrochloric acid and equiosmolar NaCl solutions in seven normal volunteers. The protocol consisted of three phases: infusion of increasing volumes (1, 3, 5 and 7 ml per min), infusion of a given volume (7 ml per min) at different stimulation sites and balloon distension. 3. At the proximal esophagus the UES response to both solutions was similar, rising from a basal resting pressure of 30 mmHg to 70 mmHg for both HCl (range 60-85 mmHg) and NaCl (55-85 mmHg). The magnitude of the response decreased as the distance from the UES increased. The level of response decreased to 40 mmHg for both NaCl and HCl (range 30-60 mmHg) at the distal esophagus. These responses were also volume dependent. When the solutions were infused at 7 ml/min into either the proximal or distal esophagus, the sphincter pressure increased with increased volume to 65 mmHg for HCl (range 50-85 mmHg) and 60 mmHg for NaCl (range 50-80 mmHg). Secondary peristalsis was also induced by the two solutions. The level of response again decreased as the distance from the UES increased. This response was also volume dependent. Esophageal distension by a balloon positioned 10 cm below the sphincter induced secondary peristalsis and sphincter response identical to those induced by the infusion of fluid. 4. These results indicate that the principal stimulus for recruitment of the esophageal motor clearance mechanism is intraluminal distension and not necessarily the pressure of intraluminal acid.

Effect of surgical treatment on the cellular immune response of gastric cancer patients.

Patients with gastric cancer have a variety of immunological abnormalities. In the present study the lymphocytes and their subsets were determined in the peripheral blood of patients with gastric cancer (N = 41) both before and after surgical treatment. The percent of helper/inducer CD4 T cells (43.6 +/- 8.9) was not different after tumor resection (43.6 +/- 8.2). The percent of the cytotoxic CD8+ T cell population decreased significantly, whether patients were treated surgically (27.2 +/- 5.8%, N = 20) or not (27.3 +/- 7.3%, N = 20) compared to individuals with inflammatory disease (30.9 +/- 7.5%) or to healthy individuals (33.2 +/- 7.6%). The CD4/CD8 ratio consequently increased in the group of cancer patients. The peripheral blood lymphocytes of gastric cancer patients showed reduced responsiveness to mitogens. The defective blastogenic response of the lymphocytes was not associated with the production of transforming growth factor beta (TGF- ) since the patients with cancer had reduced production of TGF- Beta1 (269 +/- 239 pg/ml, N = 20) in comparison to the normal individuals (884 +/- 175 pg/ml, N = 20). These results indicate that the immune response of gastric cancer patients was not significantly modified by surgical treatment when evaluated four weeks after surgery and that the immunosuppression observed was not due to an increase in TGF- 1 production by peripheral leukocytes.

A functional study of caustic strictures of the esophagus in children.

The objective of the present study was to assess esophageal motor function in 21 children (7.5 +/- 2.9 years) with caustic strictures. Esophageal manometry was performed using a water-infusion system interfaced with a polygraph and displayed on a computer screen. The data were compared with those obtained from 9 healthy children. Radionuclide transit was determined by studying deglutition of a single bolus of 99mTc pertechnetate in 10 ml of water. Non-peristaltic low-amplitude and long-duration waves were the most common findings detected in patients with strictures longer than 20% of esophageal length (N = 11). Compared with the control group, these patients presented lower mean amplitude and longer mean duration of waves (24.4 +/- 11.2 vs 97.9 +/- 23.7 mmHg, P < 0.05, and 6.7 +/- 2.4 vs 1.6 +/- 0.1 s, P < 0.05, respectively). Six patients presented low-amplitude waves just below the constricted site. Ten children presented delayed esophageal transit. There was an association between dysphagia and abnormalities on manometry (P = 0.02) and between symptoms and scintigraphy data (P = 0.01). Dysphagia in caustic strictures is due to esophageal motility abnormalities, which are closely related to the scarred segment.

[Importance of upper digestive endoscopy using lugol dye solution for the diagnosis of superficial esophageal cancer and dysplasia in patients with head and neck neoplasms]. / A importância da endoscopia digestiva alta com solução de lugol no diagnóstico de câncer superficial e displasia em esôfago de doentes com neoplasias de cabeça e pescoço.

Head and neck cancer has a high incidence in Brazil, with cancer of the oral cavity being one of the five most common cancers among Brazilians. Alcohol and tobacco consumption may contribute to synchronous or metachronous head and neck cancer and esophageal cancer. A prospective study involving 60 patients with head and neck cancer was carried out at the State University of Campinas--UNICAMP, Campinas, SP, Brazil to screen for superficial esophageal cancer and dysplasia using endoscopy and a 2% lugol dye solution followed by biopsy of the suspicious areas. Five patients (8.3%) had superficial esophageal cancer, which was diagnosed as intraepithelial carcinoma in three of them (5.0%). In four patients, the superficial esophageal cancer was synchronous and in one it was metachronous to head and neck cancer. Five patients (8.3%) had dysplasias in the esophageal epithelium (three were classified as mild and two as moderate). These results demonstrate the value of endoscopic screening of the esophagus using lugol dye in patients with head and neck cancer, particularly since superficial esophageal cancer is extremely difficult to detect by conventional methods in asymptomatic patients.

[Association of gastroduodenal mucosa lesions and varices as a cause of upper digestive hemorrhage. Retrospective study at a university hospital]. / Associação entre lesões de mucosa gastroduodenal e varizes como causa de hemorragia digestiva alta. Estudo retrospectivo em hospital universitário.

During the period from August 1st, 1990 to June 15, 1992, 117 patients with portal hypertension and upper gastrointestinal bleeding were examined at the "GASTROCENTRO"--State University of Campinas--UNICAMP, Campinas, SP, Brazil few hours after hospital admission. The objectives were to study the association of gastroduodenal acute lesions and esophageal varices. The predominant ages were thirties and sixties years (83.76%), being 70.08% of males. The hematemesis occurred in 94.02% of the cases. The etiologies of the bleeding were: esophageal varices, 47.87%; gastroduodenal acute mucosal lesions, 34.19%; gastric varices, 9.4%; gastric ulcers, 5.98% and duodenal ulcers, 2.56%. The authors concluded that exists a significant association of acute gastroduodenal lesions and esophageal varices causing upper gastrointestinal bleeding. It is essential to examine early and in detail the gastroduodenal mucosa during upper digestive endoscopy in the patient with portal hypertension and esophageal varices to diagnose the etiology of the bleeding. It is advisable to perform endoscopic examination twice a year when the dyspeptic symptoms are constant, with previous treatment for gastroduodenal acute mucosal lesions or peptic ulcers, and annual in the others.

[Incidence and epidemiology of Barrett's epithelium at the Gastrocentro-UNICAMP]. / Incidência e epidemiologia do epitélio de Barrett no gastrocentro-UNICAMP.

It is very important in the clinical practice to identify the individuals with Barrett's esophagus, because they are at risk to develop adenocarcinoma in the columnar epithelium. The objective of this research is to verify the incidence of this specific kind of epithelium at the "Gastrocentro", at State University of Campinas-UNICAMP, Campinas, SP, Brazil, among the total of 15,976 upper digestive endoscopies, performed from january of 1992 to December of 1995. From the total examinations performed were identified 2,381 patients (14.9%) presenting reflux esophagitis (grades I-IV, Savary-Miller). Among this group of patients, the endoscopist suspected of Barrett's esophagus in 110 cases (4.6%) and biopsed the distal esophagus. However, only in 85 cases (77.3%) the pathologist confirmed the diagnosis of Barrett's epithelium. The patients with Barrett's esophagus were 53 males (62.3%), presenting the mean age of 52.2 years and the following grades of esophagitis: grade I-33 cases (38.8%); grade II-15 cases (17.7%); grade III-15 cases (17.7%), grade IV-12 cases (14.1%) and without esophagitis-10 cases (11.7%). The incidence of Barrett's esophagus among the patients with reflux esophagitis was 3.57%, and among the total of examinations performed at the "Gastrocentro" during the period of four years was 0.53%, totalizing 22,4 cases/100,000 habitants.

[Conservative treatment of benign esophageal strictures using dilation. Analysis of 500 cases]. / Tratamento conservador das estenoses benignas do esôfago através de dilatações. Análise de 500 casos.

UNLABELLED: The benign esophageal stenoses (BES) are common complications owing to many etiologies: gastroesophageal reflux, ingestion of corrosive agents, esophageal surgery, radiotherapy, postendoscopic variceal sclerotherapy, drug ingestion, prolonged nasogastric intubation, extrinsic compression and esophageal webs. Esophageal dilatations are worldwide recommended to treat this complication, employing dilators of many types and diameters and facilitating the food ingestion. PURPOSE: Evaluation of the results and advantages of the conservative treatment of the BES using esophageal dilatations, in outpatient service of upper digestive endoscopy. METHODS: During the period from 1981 to 1999, 500 patients with BES were treated and followed up at the Gastrocenter - UNICAMP, in an individually Program of Esophageal Dilatation for each case. The highest number of cases was under ages from 31 to 60 years old (52,8%), and males (59,2%). The most predominant etiologies were: peptic stenosis (30,4%), caustic ingestion (23,6%), anastomosis (23,2%), megaesophagus (8,0%) and prolonged nasogastric ingestion entubation (6,4%), totalizing 91,6% of the BES. Most of patients (94,2%) were submitted to the maximum of 25 dilations. Dilators from 10,5 to 16 mm were employed in 95,6% of the cases. The duration of the treatment was 24 months in 76,2% of the BES. Esophageal perforations occurred in 6 patients (1,2%), without mortality. RESULTS: Were considered excellent, good and bad results, respectively in 76,2%, 18,2% and 5,6% of the cases. On the other hand, excellent results were recorded in 81,0% of the peptic stenosis, 66,1% of the caustic stenosis and 82,7% of the anastomotic stenosis. The conservative treatment failed in 9,3% of the caustic stenosis, 4,3% of the anastomotic stenosis and 3,9% of the peptic stenosis. Thus, the caustic stenosis were unsuccessfull in the highest percentage of unsuccessful. CONCLUSION: The conservative treatment using guidewire dilators (Savary-Gilliard and Eder-Puestow) is the first choice in the BES, is effective for long time, with short complications and the surgical treatment is indicated only when the dilatations failed.

[Videolaparoscopic surgical treatment of gastroesophageal reflux disease: modified Nissen technique - clinical and functional results]. / Tratamento cirúrgico videolaparoscópico da doença do refluxo gastroesofagiano: técnica de Nissen modificada - resultados clínicos e funcionais.

BACKGROUND: Gastroesophageal reflux disease is highly common worldwide and surgical treatment is being indicated more frequently. Currently, laparoscopic is the access of choice and several antireflux techniques may be used. We prefer a modified Nissen technique. PURPOSE: To analyze preoperative clinical and functional parameters and compare with postoperative outcome of a modified valve technique performed by laparoscopy. METHODS: A group of 59 patients underwent laparoscopic modified Nissen valve. Preoperative diagnosis was made by radiological contrast exams and endoscopy in all patients. Esophagus manometry was performed in 35 patients and scintigraphy scan in 15 patients. Complicated esophagitis occurred in 54.2%, with 21 (35.6%) patients presenting a Barrett's epithelium. Laparoscopic surgery was performed in all patients with no conversion to open surgery, with an average time of 123.9 minutes. RESULTS: There were no intraoperative complications. Hospital discharge occurred in an average of 47.6 hours. Symptoms as dysphagia, pain, regurgitation and flatus occurred in 48.1% of the patients in the first thirty days. Average follow-up was 20.8 months. Postoperative radiological, endoscopic, manometric and scintigrafic scan exams showed a significant improvement, as well as clinical assessment using Visick's classification, which showed excellent and good results in 93.1% of the patients. CONCLUSION: Comparative analysis of clinical assessment and exam results lad us to conclude that modified Nissen surgery by laparoscopic access corrects gastroesophageal reflux in most patients followed-up.

[Laparoscopy in the diagnosis of intra-abdominal diseases. Analysis of 168 cases]. / A laparoscopia no diagnóstico das doenças intra-abdominais. Análise de 168 casos.

UNLABELLED: The laparoscopy has been more and more frequently indicated in the last years, for the complementary diagnosis of intraabdominal diseases and abdominal repercussion of systemic diseases. Modern equipaments including videolaparoscopy and the use of either forceps or biopsy needle permit higher safety and significant diagnostic capacity. PURPOSE: To perform laparoscopy for the diagnosis of intraabdominal and sistemic diseases. METHODS: During the last 9 years 168 patients were submitted to laparoscopy and the main indications were: ascites--43 cases (25.5%); liver diseases--42 cases (25%); gastric cancer--37 cases (22%); lymphoma--17 cases (10.1%); abdominal tumour--9 cases (5.4%); peritoneal tuberculosis--8 cases (4.8%); liver tumour--6 cases (3.6%); mesenteric cyst--1 case (0.6%) and other diseases--5 cases (3.0%). Ninety nine patients were male (58.9%) aging from 9 to 78 years old (median 47.6 years). Liver biopsies were performed in 92 cases (54.7%) and other tumour biopsies in 26 cases (15.4%). RESULTS: The diagnosis of the diseases were established or confirmed by laparoscopy in 145 patients (86.3%). In 25 cases of gastric cancer (67.5%) laparoscopy contraindicated the laparotomy, owing to advanced disease. Two patients presented bleeding (1.2%) after liver biopsies and laparotomy was immediately indicated. One of them, whose diagnosis was systemic lupus, presented abdominal abscess, bronchopneumony and died (0.6%). CONCLUSION: Laparoscopy has small number of complications, and when employed as a diagnostic complementary method therapeutic procedures, avoids laparotomies and accelerate therapeutic procedures.

Heller's myotomy for achalasia: is an added anti-reflux procedure necessary?

Literature review (1970-85) indicates excellent or good results following Heller's operation in 89 per cent of 5002 patients. The overall mortality was 2.8 per cent with a reoperation rate of 2.8 per cent. When the operation was done through an abdominal incision, gastro-oesophageal reflux was almost twice as common as when it was done through a thoracic incision, regardless of whether an anti-reflux procedure was performed.

Functional relationships between cricopharyngeal sphincter and oesophageal body in response to graded intraluminal distension.

Responses of the cricopharyngeal sphincter to graded intraluminal distension were studied in order to determine its response threshold and to define the functional relationship between the sphincter and oesophageal body. Nine normal subjects underwent manometric study using a multilumen tube with an attached inflatable balloon sited 10 cm below the sphincter. Sphincteric and oesophageal motor responses to six graded balloon inflations were recorded in each subject. The sphincter responded to distension with increasing rise in pressure, from a median value of 42.5 mmHg at lowest levels of distension to 95 mmHg at maximal tolerated distension. Non-swallow related contractile activity was stimulated in the oesophageal body proximal to the distension and increased in quantity as inflation progressed. Distal propagation of this secondary activity was progressively inhibited with increasing distension. These interrelated changes thus show the normal upper oesophageal clearance responses to intraluminal distension. It is suggested that their more widespread application, in addition to standard manometric techniques, might provide a more rational evaluation of those patients suspected to have impaired oesophageal clearance, but in whom standard manometry is non-diagnostic.

Studies of the oesophageal clearance responses to intraluminal acid.

Contraction of the upper oesophageal sphincter combined with secondary peristalsis clears the oesophagus of refluxed gastric contents and protects the trachea, but the nature of these reflex stimuli remains controversial. Secondary peristaltic and sphincteric responses were measured during intraluminal infusion of 0.1 N hydrochloric acid and equiosmolar saline solutions in seven normal volunteers. Responses to a single volume infused at varying sites in the oesophagus and to progressively increasing volumes of test solution were measured. In addition oesophageal responses to similar degrees of distension induced by inflation of an intraluminal balloon were also recorded. The sphincteric responses to both stimuli were similar, decreasing in value with distance from the sphincter from values of 70 (68-85) mmHg (median (range] for HCl; and 70 (55-85) mmHg for NaCl at 5 cm below the sphincter to 40 (30-60) mmHg for both HCl and NaCl at 20 cm. As the volume of the solution infused into the proximal oesophagus was increased, the sphincter pressure also rose from a median basal value of 30 (25-50) mmHg to 40 (30-50) mmHg for HCl and NaCl after 1 ml, while after 7 ml infusion, the responses were greater, 65 (45-85) mmHg for HCl, and 60 (45-80) mmHg for NaCl. In the more distal oesophagus, responses were qualitatively similar but quantitatively smaller than proximally, being 30 (25-40) mmHg for HCl and 30 (25-50) mmHg for NaCl following 1 ml and 45 (40-55) mmHg for HCl and NaCl after 7 ml. Secondary peristalsis was also induced equally by both solutions and varied with volumes infused and site of infusion in a manner similar to the sphincter responses. After a 7 ml/min acid infusion 14 (1- 40) secondary contractions/three min were recorded at 5 cm and eight (2 - 18)/three min were recorded at 20 cm. Values for saline were similar, 13 (1- 38)/three min at 5 cm and eight (4 - 25)/three min at 20 cm. Oesophageal distension by a balloon positioned 10 cm below the sphincter induced identical clearance responses to those seen after similar volumes of either acid or saline infused at the same site. These results suggest that the principal stimulus for upper oesophageal clearance is intraluminal distension and do not support the idea that the oesophagus is pH sensitive.

Experimental esophageal carcinogenesis: technical standardization and results.

The aim of this research was to determine the occurrence of epidermoid carcinoma of the esophagus induced by diethylnitrosamine (DEN) in Wistar rats. DEN was administered (250-300 g) in drinking water (10 mg/kg body weight) to four groups of rats for 72 h/week, for a duration of 90, 120, 150, or 200 days (groups T90, T120, T150, and T200). Ten animals whose drinking water did not contain DEN constituted the control group. All rats were sacrificed and their esophaguses studied macro- and microscopically. The control group did not exhibit either carcinomas or preneoplasic lesions. The T120 and T200 groups presented, respectively, 47 and 58 in situ carcinomas; 1 and 20 submucosal carcinomas (P < 0.05); 4 and 17 microinvasive carcinomas (P < 0.05); 4 and 11 advanced carcinomas (P < 0.05); and 1 and 1 cases of benign hyperplasia. Pulmonary and liver carcinomas were also found in the T200 group. The majority of advanced macroscopic lesions in the T200 group were polypoid, exophytic, and not microscopically invasive in the esophageal wall. This research confirms the effectiveness of the DEN in bringing about carcinogenesis in the Wistar rat esophagus and also shows that the lesions are dosage dependent.

[The gastroduodenal mucosa in patients with portal hypertension: correlation with blood gastrin]. / A mucosa gastroduodenal em doentes com hipertensão portal: correlação com a gastrinemia.

PURPOSE: gastroduodenal mucosa of two groups of patients with chronic liver disease was studied: schistosomotic mansoni patients (SH) and non-schistosomic patients (NSH). Results were compared to serum-gastrin levels. TYPE: prospective study. PLACE: Unicamp University Hospital (Hospital das Clínicas), Campinas, São Paulo, Brazil. PATIENTS: 24 patients were included in the results, out of 26 patients studied. Two groups of study: 12 patients with schistosomiasis and liver fibrosis (SH), and 12 patients with liver cirrhosis (NSH) secondary to alcoholism or to hepatitis. PROCEDURES: esophagogastroduodenoscopies and biopsies of gastric antrum and duodenum. Function tests of the liver were also studied. RESULTS: results of gastrinemia were found within normal ranges in both groups. Student test ("t") did not show differences between groups at the 5% level. However, patients with chronic liver cirrhosis had more significant and severe endoscopic findings and chronic inflammatory processes of the gastroduodenal mucosa (acute gastritis, duodenitis and ulcers) than patients with liver fibrosis. CONCLUSIONS: patients with liver cirrhosis due to high risk of gastroduodenal bleeding should be maintained under continuous vigilance, appropriate diet and mucosa cytoprotectors. Furthermore, more research is required to study the etiology of gastroduodenal lesions in these specific groups of patients.