P53 and Ki-67 overexpression in gastroesophageal reflux disease--Barrett's esophagus and adenocarcinoma sequence.

Gastroesophageal reflux disease (GERD) is a major risk factor for the development of esophageal adenocarcinoma (ACE). Many molecular alterations occur in esophageal carcinogenesis, yet the exact mechanism of ACE development remains unknown. This study aims to determine p53 protein and Ki-67 expression in esophageal mucosa of patients with GERD and study the correlation between these markers and the progression from normal squamous epithelium to esophagitis, columnar epithelium with or without intestinal metaplasia and ACE. We analyzed p53 protein and Ki-67 expression in biopsies of 200 patients with GERD and 35 patients with ACE. Those biopsies were classified into five groups: (i) G1 normal squamous epithelium (58); (ii) G2 esophagitis (80); (iii) G3 columnar epitheliums without intestinal metaplasia (30); (iv) G4, columnar epitheliums with intestinal metaplasia (32); and (v) G5 ACEs (35). p53 protein overexpression was found in 7% (4) of G1, 37.5% (30) of G2, 30% (9) of G3, 62.5% (20) of G4, and 71.4% (25) of G5 (p < 0.001). Ki-67 index increased according to the severity of histopathological diagnoses. Ki67 index was 21.3 +/- 19.5% in G1, 38.8 +/- 24.9% in G2, 37.7 +/- 26.3% in G3, 52.8 +/- 24.6% in G4, and 57.1 +/- 25.1% in G5 (P < 0.001). Linear correlation between p53/Ki67 expression and the multistep progression from squamous epithelium to ACE was observed (P < 0.001 and P < 0.05). Our results indicate that overexpression of p53 and increased Ki-67 could be associated with the development and progression to ACE in patients with GERD.

Heartburn during sleep: a clinical marker of gastro-oesophageal reflux disease in morbidly obese patients.

Gastro-oesophageal reflux disease (GORD) and morbid obesity are entities with increasing prevalence. New clinical strategies are cornerstones for their management. The aim of this study was to assess the prevalence of heartburn during sleep (HDS) and whether this symptom predicts the presence of objective GORD parameters and increased heartburn perception in morbidly obese patients. Ninety-one consecutive morbidly obese patients underwent clinical evaluation, upper gastrointestinal endoscopy and oesophageal pH monitoring. HDS was characterized when patients replied positively to the question, 'Does heartburn wake you from sleep?'. A General Score for Heartburn (GSH) ranging between 0 and 5 was assessed with the question 'How bad is your heartburn?'. HDS was reported by 33 patients (36%). More patients with HDS had abnormal acid contact time or reflux oesophagitis than patients without HDS (94%vs 57%, P < 0.001). HDS had a positive predictive value of 94% (0.95 CI 82-98), sensitivity of 48% (0.95 CI 37-60%) and specificity of 93% (0.95 CI 77-98%) for detection of GORD. A higher proportion of patients with HDS perceived heartburn preceded by acid reflux in diurnal (39%vs 9%; P < 0.001) periods during pH-metry. HDS patients showed higher GSH (2.4 +/- 0.5 vs 1.7 +/- 0.4; P < 0.0001) compared with patients who denied HDS but reported diurnal heartburn. HDS occurs in a significant minority of patients with morbid obesity and has high positive predictive value for GORD. Symptomatic reflux during the sleep seems to be a marker of increased heartburn perception in this population.

c-Myc overexpression is strongly associated with metaplasia-dysplasia-adenocarcinoma sequence in the esophagus.

We aim to determine the expression of the proto-oncogene c-Myc in patients with Barrett's esophagus (BE) and esophageal adenocarcinoma, and to evaluate the prevalence of such expression in relation to the metaplasia-dysplasia-adenocarcinoma sequence. BE develops as a result of a severe esophageal mucosa injury from gastroesophageal reflux. BE is a premalignant lesion and plays an important role in the development of esophageal adenocarcinoma. Several genetic alterations have been identified in the process that transforms a normal cell into a tumorous one. In the development of human tumors, one of the most important genes is the proto-oncogene c-Myc. The c-Myc protein expression was determined by immunohistochemical analysis in four different groups: 31 patients with normal tissue, 43 patients with BE without dysplasia, 11 patients with dysplasia in BE and 37 patients with esophageal adenocarcinoma. The material was obtained from esophageal biopsies or the dissection of patient esophagectomy specimens. Demographic and endoscopic data (sex, age, race and intestinal metaplasia extension), and morphologic and histopathologic tumor characteristics (deep tumor invasion, lymph node status, and tumor differentiation) were analyzed. The c-Myc expression was assessed using the Immunoreactive Scoring System (IRS). Overexpression of c-Myc was found in only 9.6% of normal tissue specimens, 37.2% of Barrett's esophagus, 45.5% of BE patients with dysplasia and 73% of adenocarcinoma samples, with significant statistical difference among these groups. No correlation was identified when the c-Myc expression was compared with morphologic and histologic tumor features or endoscopic data. However, linear correlation of c-Myc overexpression along the metaplasia-dysplasia-adenocarcinoma sequence was observed. This study demonstrates a significant increase in the expression of c-Myc in Barrett's esophagus, dysplasia and adenocarcinoma in relation to the control group, as well as a linear progression of this gene expression in this sequence. These results point out the importance of this marker in the development of esophageal adenocarcinoma from BE.

Prognostic value of p53 protein expression and vascular endothelial growth factor expression in resected squamous cell carcinoma of the esophagus.

The most common genetic alterations found in a wide variety of cancers are p53 tumor suppressor gene mutations. p53 appears to be a nuclear transcription factor that plays a role in the control of cell proliferation, apoptosis, and the maintenance of genetic stability. Angiogenesis is a critical process in solid tumor growth and metastasis. Vascular endothelial growth factor (VEGF), a recently identified growth factor with significant angiogenic properties, may be a major tumor angiogenesis regulator. Few studies have investigated the association between p53 and VEGF expressions and prognosis in esophageal carcinoma. Forty-seven specimens resected from patients with stage II and III squamous cell carcinoma (SCC) of the esophagus were studied using immunohistochemical staining. VEGF and p53 expressions were observed in 40% and 53% of the tumors, respectively. The p53 and VEGF staining statuses were coincident in only 21% of the tumors, and no significant correlation was found between p53 and VEGF statuses. No clinicopathologic factors were significantly correlated with p53 or VEGF expression. No significant association between p53 and VEGF expressions and poor prognosis was found. In conclusion, p53 and VEGF were not correlated with prognosis in patients with stage II and III SCC of the esophagus.

Survival and prognostic factors in patients with resected epidermoid oesophageal carcinoma.

To determine long-term survival of patients with thoracic oesophageal tumor who underwent resection, and to identify possible associated prognostic factors, 58 patients underwent oesophagectomy alone (group A) and 16 combined with neo-adjuvant chemoradiotherapy (group B). Univariate and multivariate analysis of prognostic factors were performed for age, depth of oesophageal wall tumour penetration, node involvement, type of resection, TNM stage and degree of tumour differentiation. Long-term survival rates at 1-5 years were 81% versus 89%; 56% versus 67%; 30% versus 67%; 12% versus 44%; and 0% versus 33% for group A and B, respectively (P = 0.0543, NS). Univariate analysis revealed only depth of invasion (P = 0.0076) and TNM stage (P = 0.0452) as isolated prognostic factors for long-term survival and multivariate analysis did not demonstrate any independent factor. Despite the small number of cases, neoadjuvant chemoradiotherapy seems to improve prognosis as well as to allow resection in a greater number of cases due to tumor downstaging.

Induction of esophageal carcinogenesis by diethylnitrosamine and assessment of the promoting effect of ethanol and N-nitrosonornicotine: experimental model in mice.

It is known that some nitrosamines preferably affect particular organs because of their organospecificity. Diethylnitrosamine (DEN) is one of the most powerful nitrosamines for experimentally inducing esophagus cancer. The present study aimed to evaluate the rate and type of epithelial lesions induced by DEN in mice. We also assessed the role of alcohol and N-nitrosonornicotine (NNN) as promoters of this carcinogenesis. A total of 208 female mice (Mus musculus) were allocated to five experimental groups: group 1, water only (controls); group 2, DEN + water; group 3, DEN + NNN; group 4, DEN + 6% alcohol solution; group 5, DEN + NNN + 6% alcohol solution. Animals in groups 2, 3, 4 and 5 received DEN (0.04 ml/l) three times per week, and during the following 4 days they received the other solutions. NNN was provided at a final concentration of 30 mg/l. The overall experimental period was 180 days. At the end of this time, the animals were killed and their esophagus was dissected for macro- and microscopic analysis. There was no significant difference in relation to the size of the esophagus and to the average DEN intake by the animals (p > 0.05). A statistically significant difference (p < 0.0001) was observed between controls and all other experimental groups. There was no significant difference among experimental groups treated with carcinogens (p > 0.05). The average incidence of cancer was 85.4%. The experimental model used in the present study is a very potent indicator of esophagus cancer. Owing to the high incidence for cancer observed in the present study, it was not possible to assess the effect of alcohol and NNN as inducers for the development of esophageal cancer.

Alternative surgical treatment for complex enterocutaneous fistula.

A retrospective analysis on the clinical-surgical handling of patients with enterocutaneous fistula (ECF) was performed, where an alternative surgical technique was discussed: intestinal bypass. Fistula with draining over 500 ml/24 h, which were present in 13 patients, were classified as high debit. We defined as complex, the fistula with multiple orifices, high defect of the abdominal wall or through the mesh. The population studied consisted of 25 patients, 11 male, in a total of 34 ECF and mean age of 41.9 years. At clinical treatment with TPN for high debit ECF, 2 patients (16.6%) were cured, another 2 died and 8 (66.8%) needed surgical treatment. The surgery cured 7 patients (77.7%) with high debit ECF but 2 (22.3%) died. In the patients with low debit ECF, TPN cured 2 patients (40%) but failed in another 3 (60%). All patients with low debit ECF resolved with surgical treatment.

Efficacy of computed axial tomography in the evaluation of the involvement of the respiratory tract in patients with squamous cell carcinoma of esophagus.

Squamous cell carcinoma of the esophagus is endemic in Rio Grande do Sul, the most southern state of Brazil, where the incidence reaches 27 out of 100,000 inhabitants per year. Palliative treatments, surgical or nonsurgical, impose lower mortality and lower costs. The choice of the best treatment for each patient depends on the neoplasia staging, and the local involvement of the tracheobronchial tree by tumor characterizes incurability. Computed axial tomography (CAT) is indicated, but remarkable contradictions were found in the literature. We studied 134 patients, diagnosed with esophageal squamous cell carcinoma, who underwent computed tomography and fiberoptic bronchoscopy (gold standard) performed with an uniform technique. An accuracy of 85.1% was obtained when computed tomography was compared with bronchoscopy with regard to impingement, displacement and invasion of trachea and bronchi. In conclusion, there is no statistically significant difference between computed tomography and fiberoptic bronchoscopy in the evaluation of tracheobronchial involvement by squamous cell carcinoma of the esophagus (p < 0.05).

Laparoscopic approach to wandering spleen: a case report and an update to the question.

Wandering spleen is seldom seen in everyday situations, and its prevalence is not well defined in the literature. Its causes are not precisely known, and there is controversy over its management. A 34-year-old woman experienced low-intensity abdominal pain associated with a palpable hypogastric mass, which was confirmed by imaging studies to be a wandering spleen. Because of ureteral compression, a surgical approach was decided upon, and videolaparoscopic splenectomy was chosen. This technique, comments about specific technical issues, and other treatment options presented in the literature are discussed. Videolaparoscopic splenectomy has excellent surgical results, both functional and aesthetic.

The influence of reperitonization on the induction of formation of intraperitoneal adhesions by a polypropylene mesh prosthesis. An experimental study in rats.

The correction of groin hernias has increasingly been performed by transperitoneal videolaparoscopic methods, using a polypropylene mesh. This could lead to an increased incidence of adhesion formation. The incidence of adhesions induced by mesh placement and the influence of reperitonization was observed on 40 male adult Wistar rats. Adhesions were significantly more common on the groups in which the prosthesis was placed (59% vs 95%; p = 0.01), as well as on the groups in which reperitonization was performed (58% vs 100%; p = 0.03). The results suggest that polypropylene mesh placement and reperitonization are each independent factors in the induction of adhesions formation.

Delayed cervical anastomosis of the esophagus for esophageal carcinoma.

BACKGROUND: The surgical approach for patients with advanced epidermoid esophageal carcinoma should provide an effective palliative effect with morbidity ratio as low as possible. Anastomotic leakage is a frequent complication and may be responsible for both early and late morbidity and, therefore, we assessed the role of delayed cervical esophagovisceral anastomosis technique in relation to the incidence of anastomotic complications. METHODS: Eight patients (Group 1) and 12 patients (Group 2) submitted to one-stage or two-stage operation, respectively, were selected by an intraoperative assessment by the surgeon, considering mainly tissue blood flow of the replacement organ after its placement in the cervical region. RESULTS: In Group 1 anastomotic dehiscence was observed in 37.5% of patients, while in Group 2 no cases of dehiscence occurred (p = 0.049). However, the postoperative mortality rate did not differ between the two groups (12.5% versus 0%, NS). CONCLUSION: When organ viability is uncertain, esophagovisceral anastomosis is best done by two-stage operation, since it decreases the incidence of anastomotic leak.