Recurrent acute thermal lesion induces esophageal hyperproliferative premalignant lesions in mice esophagus.

Hot beverage consumption is a risk factor for esophageal squamous cell carcinoma, but the underlying mechanisms are still unknown. We developed an experimental mouse model to understand the mechanism of thermal lesion to esophageal carcinogenesis. Female BALB/c mice were treated by gavage with water at different temperatures three times a week and nitrosamines in the drinking water. Water at 70°C, but not at lower temperatures, initially induced an esophageal necrosis that healed and became resistant to necrosis after further administrations. However, when 70°C water was associated with N-nitrosodiethylamine at doses above 1 ppm, there was interference in epithelial regeneration, allowing recurrent thermal injury and inflammation. Recurrent thermal injury resulted in hyper proliferative premalignant lesions being induced earlier (at 4 weeks) and at a higher frequency (4-fold increase at 16 weeks) when compared to mice treated with NDEA only. Ki-67 immunostaining revealed that recurrent thermal injury induced basal cell proliferation resulting in the expansion of epithelial basal cells, confirmed by the increase in cytokeratin 14 positive cells with concomitant reduction of differentiated cytokeratin 5 positive cells. We conclude that recurrent thermal lesion may act as a tumor promoter though a strong proliferation stimulus of esophageal epithelial basal cells.

Kidney transplantation in children weighing less than 15 kg: extraperitoneal surgical access-experience with 62 cases.

Small children are a challenging group in whom to perform KT. This retrospective study analyzed the results of 62 KTs in children weighing <15 kg, performed between 1998 and 2010, using extraperitoneal access and anastomosis of the renal vessels of donors to the aorta and IVC or iliac vessels of the recipients. Thirty-two (51.6%) grafts were LRDTs and 30 (48.4%) were DDRTs-28 of them pediatric. The mean age at KT was 3.7 ± 2.2 yr (1-12), and the mean weight was 12.3 ± 2.1 kg (5.6-14.9). Ten children weighed <10 kg, and five (8.1%) children presented previous thrombosis of the venous system. At one and five yr, patient survival was 93.2% and 84.2%, and graft survival was 85.2% and 72.7%. There were no differences between the rates for LRDT and DDRT. There were six vascular complications (four vascular thromboses, one laceration, and one renal artery stenosis) and two perirenal collections. Extraperitoneal access is a valid KT technique in children weighing <15 kg.

Fructose 1-6 bisphosphate versus University of Wisconsin solution for rat liver preservation: does FBP prevent early mitochondrial injury?

BACKGROUND: Fructose 1,6-biphosphate (FBP) has been shown to exert therapeutic effects in models of ischemia-reperfusion in organs other than the liver. This study compared FBP and University of Wisconsin (UW) solution during cold storage and reperfusion, among mitochondria of adult male Wistar rat livers. METHODS: Adult male Wistar rats were assigned to two groups according to the preservation solution used; UW or FBP Aspartate transaminase (AST), alanine transferase (ALT); and lactic dehydrogenase (LDH) were measured in samples of the storage solution obtained at 2, 4 and 6 hours of preservation. After 6 hours of cold storage, we reperfused the liver, taking blood samples to measure AST, ALT, LDH, and throbarbituric acid reactive substances (TBARS). Hepatic fragments were processed for histologic analysis; for determinations of TBARS, catalase, and nitric oxide as well as for mitochondrial evaluation by infrared spectroscopy. RESULTS: During cold preservation, levels of AST and LDH in the storage solution were lower among the FBP group, but after reperfusion, serum levels of AST, ALT, and LDH were higher in this group, as was catalase activity. TBARS and nitric oxide were comparable between the groups. In the UW group there was a higher amide I/amide II ratio than in the FBP group, suggesting an abnormal protein structure of the mitochondrial membrane. No signs of preservation injury were observed in any liver biopsy, but sinusoidal congestion was present in livers preserved with FBP. CONCLUSION: FBP showed a protective effect for preservation during cold storage seeming to protect the mitochondrial membrane although it did not prevent reperfusion injury.

Endoscopic implantation of polymethylmethacrylate augments the gastroesophageal antireflux barrier: a short-term study in a porcine model.

BACKGROUND AND AIMS: Endoscopic injection of filler agents into the esophagogastric junction has been developed to augment the antireflux barrier and decrease gastroesophageal reflux (GER). However, evidence of efficacy is lacking and serious complications have been reported in humans. The aim of this study was to assess whether endoscopic implantation of polymethylmethacrylate augments the antireflux barrier in a porcine model for GER. METHODS: Large White pigs underwent esophageal manometry, gastric yield pressure (GYP), and gastric yield volume (GYV) measurements and implantation of PMMA in the distal esophagus under general anesthesia. After follow-up of 28 days, esophageal manometry and gastric yield measurements were repeated and animals sacrificed. RESULTS: Implantation of PMMA was performed in 18 animals, and 14 animals survived 28 days. There was a significant increase in GYP (10.7 mmHg versus 8.1 mmHg; p = 0.017) and GYV (997 ml versus 393 ml; p < 0.001) after PMMA implantation, whereas resting LES pressure did not change significantly. Acute inflammatory changes and fibrous tissue deposits were found surrounding the PMMA implants during histology. One animal died after esophageal perforation and three others due to pneumonia (two) and colon perforation (one) in the postoperative period. CONCLUSIONS: Endoscopic implantation of PMMA in the distal esophagus augments the antireflux barrier 28 days after the procedure. However, esophageal perforation points to the need for technical refinements to make the procedure safer.

Hepatic reperfusion in rats: a new model with portal arterialization in studying early ischemia-reperfusion injury.

Isolated liver perfusion has been used to evaluate the beneficial effects of several agents. In the present study, we developed a model using a recipient rat to reperfuse harvested livers in an ex situ, in vivo recirculating system. A total of 25 reperfusion procedures using adult male Wistar rats as donors and recipients were done. The preservation of the livers was performed with University of Wisconsin solution for 6 hours. Thereafter, the liver was reperfused with blood from another rat. We believe that the model presented herein offers an alternative method to evaluate early hepatocellular damage or hepatic microcirculation.

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.

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.

Monitor de pressão e volume gástricos: estudo experimental em suínos / Monitor pressure and gastric volume: an experimental study in pigs

The gastric pressure monitor was developed by the Biomedical Engineering Div. of the HCPA. It helps to evaluate Gastric Yield Pressure (GYP) in a swine model for gastroesophageal reflux (GER). A dual lumen 20 Fr Foley catheter is passed through a gastrostomy into the swine stomach...

Fish Balistes capriscus skin extract-induced relaxation in mesenteric arterial bed of rat.

The vasorelaxing activity of the aqueous extract of fish Balistes capriscus skin (AEBc) on mesenteric arterial bed (MAB) of rats was studied. The bolus injections of AEBc (bolus of 5.1, 10.2, 20.5, and 41.1mg) significantly inhibited, in a concentration-dependent manner, the maximal contractile response induced by methoxamine (30 microM) in MAB. The vasodilatation action of AEBc is not mediated through beta-adrenoceptors or cyclo-oxigenase, since it was not affected by propranolol (20 microM) or diclofenac sodium (3 microM). The vasodilator response induced by subsequent addition of AEBc Balistes capriscus in bolus was significantly reduced in water infusion for endothelium removal. Treatment with an inhibitor of NO synthase (L-NAME, 10 microM) decreased AEBc effect. The guanylate cyclase inhibitor methylene blue (MB, 100 microM) had no significant effect on AEBc-induced vasodilatation. These results suggest that the vasorelaxing effect of AEBc is mediated by endothelium-dependent (NO/EDRF) and endothelium-independent neurally induced vasorelaxation from nonadrenergic and noncholinergic nerves (NO).

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.

[High temperature "matè" infusion drinking in a population at risk for squamous cell carcinoma of the esophagus]. / Mate (chimarrão) é consumido em alta temperatura por população sob risco para o carcinoma epidermóide de esôfago.

UNLABELLED: "Matè", a popular hot infusion of a herb (Ilex paraguayensis) drunk in large volumes, is a known risk factor for squamous cell carcinoma of the esophagus and there is a suspicion that high temperature of boiled water used for the infusion may contribute for carcinogenesis. METHODS: We measured the temperature of "matè" infusion drunk by a sample of the population at risk for this carcinoma in Taquara, southern Brazil. We interviewed inhabitants for drinking habits and the temperature of the infusion was measured with high precision thermometers. Temperature of the infusion was asked to consumers and their estimate compared to our measurements. We considered 60 degrees C or higher as "hot". RESULTS: In 36 residencies, 107 individuals were drinking "matè". Most individuals drank it daily (97.2%), and the medium daily volume was 1,265 ml (SD +/- 1,132 mL) ranging from 250 to 6,000 mL. The measured temperature was 60 degrees C or higher in 72% of residencies with medium of 63.4 degrees C (51-78 degrees C) and median 64.4 degrees C. CONCLUSION: In this study, "matè" was consumed in large volumes at high temperature and individuals did not estimate correctly the temperature of infusion. High temperatures of "matè" may contribute to carcinogenesis in this population.

[Prevalence of adenocarcinoma of the esophagus and esophagogastric junction in a 10 year period at a cancer referral center in southern Brazil]. / Prevalência de adenocarcinoma do esôfago e da junção esofagogástrica durante 10 anos num centro de referência para câncer no sul do Brasil.

UNLABELLED: There is increasing incidence of adenocarcinoma of the esophagus and esophagogastric junction in the USA and Europe, however, data in Brazil are scanty. OBJECTIVE AND METHODS: We reviewed all histology confirmed esophageal and esophagogastric junction cancer reports during a 10-year period (1987-1996) obtained by upper digestive endoscopy biopsies at a cancer referral center in Southern Brazil. Cancer cases were classified in three categories: adenocarcinoma, squamous cell carcinoma, and others. RESULTS: Among 349 cases, adenocarcinoma was found in 53 (15.2%), squamous cell carcinoma in 283 (81.1%) and others in 13 (3.7%). CONCLUSIONS: In this study, the prevalence of adenocarcinoma was 15%.

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.

Influence of surgically induced gastric and gastroduodenal content reflux on esophageal carcinogenesis--experimental model in Wistar female rats.

Studies in human beings and animals have shown that esophageal exposure to duodenal and gastric contents may be important for the development of Barrett's esophagus and its complications, including adenocarcinoma and epidermoid carcinoma. Diethylnitrosamine (DEN) is a carcinogen that stimulates the development of epidermoid carcinoma in the esophagus of mice. The aim of this study was to evaluate the effect of gastroduodenal and gastric content reflux on induction of esophageal carcinogenesis. Gastroesophageal reflux (GER) and gastroduodenoesophageal reflux (GDER) were produced by cardioplasty and esophagoduodenostomy. The chosen carcinogen was DEN, diluted in drinking water, given 3 days a week for 20 consecutive weeks. One hundred Wistar female rats were divided into six groups, as follows: group 1 (18 rats), cardioplasty without DEN; group 2 (18 rats), cardioplasty with DEN; group 3 (10 rats), only water; group 4 (17 rats), cardioplasty with DEN; group 5 (17 rats), esophagoduodenostomy with DEN; group 6 (20 rats), only DEN. GER in isolation induced papillomatosis or ulceration in 22.2% of rats and, when associated with DEN, induced papillomatosis in 61.1% of rats. GDER in isolation induced marked esophagitis in 61.1% of rats, Barrett's esophagus in 16.7% and esophageal adenocarcinoma in 16.7%; when associated with DEN, 23.5% of rats presented marked esophagitis, papillomatosis or ulceration, whereas 76.5% had esophageal carcinoma, with 70.6% epidermoid carcinoma and 5.9% adenocarcinoma. Rats treated with water alone did not show histologic abnormalities of the esophageal mucosa. Rats treated with DEN alone developed papillomas in 50.0% of the cases and remained histologically unchanged in 50.0%. There was no development of low- or high-grade dysplasia in any group. The conclusions are that (1) GDER is significantly more deleterious to esophageal mucosa than GER; (2) in this study, GER did not present carcinogenic potential in relation to the esophagus; (3) GDER in isolation is an esophageal carcinogen, producing Barrett's esophagus and esophageal adenocarcinoma; (4) esophageal oncogenesis caused by GDER is potentiated by DEN, inducing esophageal epidermoid carcinoma; (5) in this study, DEN in isolation did not generate tumors in the esophagus of rats.

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.

Esophageal dysplasias are detected by endoscopy with Lugol in patients at risk for squamous cell carcinoma in southern Brazil.

Diagnosis of squamous cell carcinoma of the esophagus is usually late. Staining of the mucosa with Lugol's solution during endoscopy has been suggested to identify early cancer/dysplasia and may improve prognosis. Lugol was tested during endoscopy in 96 asymptomatic subjects at risk for this tumor, who were found to have atypias after exfoliative cytology in southern Brazil. Biopsies were obtained in Lugol's 'stained' and 'unstained' areas in the esophageal mucosa and the histologic results were compared. 'Unstained' areas were present in 64 (66.7%) instances: 44 'unstained' areas over mucosa with normal appearance revealed seven dysplasias (four high and three low grade), whereas 20 'unstained' areas with visible lesions contained only one dysplasia (low grade). 'Stained' areas in 96 (100%) subjects showed two additional dysplasias (one high and one low grade). In this study, Lugol 'unstained' areas were of great value for detection of dysplasias (sensitivity = 80%; specificity = 63%; p = 0.01, Fisher's exact test; CI = 95%; odds ratio = 6.7).

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.