Antonio de Barros Lopes

Esophageal squamous cell carcinoma - precursor lesions and early diagnosis.

Squamous cell carcinoma of the esophagus (SCCE) carries a poor prognosis due to late diagnosis. Early detection is highly desirable, since surgical and endoscopic resection offers the only possible cure for esophageal cancer. Population screening should be undertaken in high risk areas, and in low or moderate risk areas for people with risk factors (alcoholics, smokers, mate drinkers, history of head and neck cancer, achalasia and lye stricture of the esophagus). Esophageal balloon cytology is an easy and inexpensive sampling technique, but the current methods are insufficient for primary screening due to sampling errors. Conventional endoscopy with biopsy remains the standard procedure for the identification of pre-malignant and early malignant changes in esophageal mucosa and endoscopic detection. It may be enhanced by several techniques such as dye and optic chromoendoscopy, magnifying endoscopy, and optical-based spectroscopic and imaging modalities. Since more than 80% of SCCE deaths occur in developing countries, where expensive techniques such as narrow band imaging (NBI) and autofluorescence imaging are unavailable, the most cost-effective tool for targeting biopsies may be Lugol dye chromoendoscopy, since it is easy, accurate, inexpensive and available worldwide. In ideal conditions, or in developed countries, is it reasonable to think that optimal detection will require a combination of techniques, such as the combination of Lugols chromoendoscopy and NBI to identify esophageal areas that require further characterization by a high resolution technique. The efficacy and cost-effectiveness will determine whether these modalities will become part of standard endoscopy practice.

Low-dose albumin in the treatment of spontaneous bacterial peritonitis: should we change the standard treatment?

We read with interest the recent paper published on the management of patients awaiting liver transplant.1 The authors carried out a comprehensive review of liver complications, including spontaneous bacterial peritonitis (SBP). They stated that intravenous albumin (IV-A) at a dose of 1.5 g/kg at diagnosis and 1 g/kg 48 h later has been shown to prevent renal impairment and reduces mortality. We would like to address this point as this benefit has only been demonstrated in one clinical trial in which an arbitrary dose of albumin was used.2 …

No evidence of HPV DNA in esophageal squamous cell carcinoma in a population of Southern Brazil

AIM To investigate the association between human papillomavirus (HPV) and esophageal squamous cell carcinoma (ESCC) in southern Brazil. METHODS We studied 189 esophageal samples from 125 patients from three different groups: (1) 102 biopsies from 51 patients with ESCC, with one sample from the tumor and another from normal esophageal mucosa distant from the tumor; (2) 50 esophageal biopsies from 37 patients with a previous diagnosis of head and neck squamous cell carcinoma (HNSCC); and (3) 37 biopsies from esophageal mucosa with normal appearance from 37 dyspeptic patients, not exposed to smoking or alcohol consumption. Nested-polymerase chain reaction (PCR) with the MY09/11 and GP5/6 L1 primers was used to detect HPV L1 in samples fixed in formalin and stored in paraffin blocks. All PCR reactions were performed with a positive control (cervicovaginal samples), with a negative control (Human Genomic DNA) and with a blank reaction containing all reagents except DNA. We took extreme care to prevent DNA contamination in sample collection, processing, and testing. RESULTS The histological biopsies confirmed the diagnosis of ESCC in 52 samples (51 from ESCC group and 1 from the HNSCC group) and classified as well differentiated (12/52, 23.1%), moderately differentiated (27/52, 51.9%) or poorly differentiated (7/52, 13.5%). One hundred twenty-eight esophageal biopsies were considered normal (51 from the ESCC group, 42 from the HNSCC group and 35 from dyspeptic patients). Nine had esophagitis (7 from the HNSCC and 2 from dyspeptic patients). Of a total of 189 samples, only 6 samples had insufficient material for PCR analysis: 1 from mucosa distant from the tumor in a patient with ESCC, 3 from patients with HNSCC and 2 from patients without cancer. In 183 samples (96.8%) GAPDH, G3PDH and/or β-globin were amplified, thus indicating the adequacy of the DNA in those samples. HPV DNA was negative in all the 183 samples tested: 52 with ESCC, 9 with esophagitis and 122 with normal esophageal mucosa. CONCLUSION There was no evidence of HPV infection in different ESCC from southern Brazil.

Is there yet any place for reagent strips in diagnosing spontaneous bacterial peritonitis in cirrhotic patients? An accuracy and cost-effectiveness study in Brazil

Background:  Diagnosis of spontaneous bacterial peritonitis (SBP) is currently based on ascitic cell counting, but there is a need for a more simple and rapid diagnostic tool. The objectives of this study are to evaluate the accuracy of reagent strips in diagnosing SBP and compare their costs with total and differential cell counts.

Stepwise expression of CDKN2A and RB1 proteins in esophageal mucosa from patients at high risk for squamous cell carcinoma.

Squamous cell carcinoma of the esophagus is a lethal cancer and carries a poor prognosis because of late diagnosis. Identification of molecular markers may aid early diagnosis. We assessed the expression of CDKN2A/RB1 in the esophageal mucosa and its association with the histology. Esophageal biopsies were collected from 38 patients with no esophageal lesion (group 1), from iodine-negative areas of 108 alcoholics/smokers (group 2), and from tumor and nontumor areas in 41 patients with squamous cell carcinoma (group 3). The histologic diagnosis was compared with immunoexpression of CDKN2A/RB1. In group 1, histology showed normal mucosa/mild esophagitis and no expression of CDKN2A/RB1. In groups 2 and 3, the diagnosis was: normal mucosa (38.4%), esophagitis (44.4%), dysplasia and carcinoma in situ (2.8%), and carcinoma (14.3%). The immunoexpression of CDKN2A/RB1 increased in a stepwise manner from the normal mucosa, to esophagitis, dysplasia/carcinoma in situ, and carcinoma (P<0.01). CDKN2A/RB1 was not expressed in the esophageal mucosa of patients without risk factors. p16/pRb expression increased in a stepwise manner, according to the severity of histologic lesions, in biopsies from patients exposed to risk factors or with carcinoma. Esophageal mucosa exposed to risk factors with the expression of those proteins may be at risk for malignant transformation.

Detecting p53 immunoexpression in esophageal mucosa with exfoliative cytology in individuals at risk for squamous cell carcinoma of the esophagus.

OBJECTIVE To determine the prevalence of p53 expression in cytologic smear collected by the RS Balloon in high-risk individuals, and test its yield in the cytologic screening of squamous cell carcinoma of the esophagus (SCCE). STUDY DESIGN Asymptomatic individuals at risk for SCCE underwent esophageal exfoliative cytology with the RS Balloon immediately followed by upper gastrointestinal endoscopy with biopsies of unstained areas after iodine mucosal staining of the esophagus. For each patient, cytologic expression of p53 was compared with the worst endoscopic biopsy diagnosis and the histologic expression of p53. RESULTS One hundred seventy-one individuals were submitted to the studys protocol. There were 8 lost cases (4.7%) due to inadequate cytologic samples. The final sample consisted of 163 individuals where 150 were male (92%), mean age of 52.6 +/- 12.0 years old. There were 3 cases of dysplasia/SCCE. Immunohistochemical expression of p53 protein was positive in 38 patients (23.6%), with basal layer expression in 29 (76.3%), middle layer expression in 8 (21.1%) and superficial layer in 1 (2.6%). All patients with dysplasia/SCCE had positive immunohistochemical expression of p53 protein. Immunocytochemical expression of p53 protein in cytologic smear was negative in all cytology samples. CONCLUSION The negative results of immunocytochemical expression of p53 protein suggest that its use does not contribute to improving the performance of conventional cytology of the esophagus in the screening for SCCE and its precursor lesions.

Lower cutoff values for dipsticks may improve their accuracy in rapid diagnosis of spontanous bacterial peritonitis

1996;24(Suppl):445A.5. Jeffries MA, Stern MA, Gunaratnam NT, Fontana RS. Unsuspected in-fection is infrequent in asymptomatic outpatients with refractory ascitesundergoing therapeutic paracentesis. Am J Gastroenterol 1999;94:2972-2976.6. RomneyR,MathurinP,Ganne-Carrie´ N,HalimiCH,MediniA,LematreP, et al. Usefulness of routine analysis of ascitic fluid at the time of thera-peutic paracentesis in asymptomatic outpatients. Gastroenterol Clin Biol2005;29:275-279.7. Castellote J, Girbau A, Maisterra S, Charhi N, Ballester R, Xiol X. Spon-taneous bacterial peritonitis and bacterascites prevalence in asymptomaticcirrhotic outpatients undergoing large-volume paracentesis. J Gastroen-terol Hepatol, in press.

Urinary Concentrations of Polycyclic Aromatic Hydrocarbon Metabolites in Maté Drinkers in Rio Grande do Sul, Brazil

Background: Consumption of maté, an infusion of the herb Ilex paraguariensis (yerba maté), is associated with increased risk of esophageal squamous cell carcinoma (ESCC), but the carcinogenic mechanism is unclear. Commercial brands of yerba maté contain high levels of carcinogenic polycyclic aromatic hydrocarbons (PAHs), which are acquired during the traditional drying process. The purpose of this study was to characterize exposure to PAHs in maté drinkers over a wide range of maté consumption. Methods: We recruited 244 adults who answered a questionnaire and collected a fasting spot urine specimen. We quantified urinary concentrations of seven PAH metabolites and assessed associations between self-reported recent maté consumption and urinary PAH metabolites by multivariate regression. Results: Recent maté consumption showed a significant dose–response association with 6 of 7 PAH metabolites in unadjusted models (Ptrend < 0.05). After adjustment for creatinine and potential confounders, concentrations of 2-naphthol, 1-hydroxyphenanthrene, and the sum of 2- and 3-hydroxyphenanthrene remained significantly associated with recent maté intake. The sum of the urinary concentrations of the phenanthrene metabolites was similar or higher among maté drinkers who did not smoke than among smokers who did not drink maté. Conclusions: Urinary concentrations of PAH metabolites were significantly associated with self-reported amounts of recent maté intake, and drinking maté increased urinary concentrations of some PAH metabolites as much as smoking cigarettes. Impact: Drinking maté is a source of exposure to potentially carcinogenic PAHs, consistent with the hypothesis that the PAH content of maté may contribute to the increased risk of ESCC in maté drinkers. Cancer Epidemiol Biomarkers Prev; 27(3); 331–7. ©2017 AACR.

3549 Recurrence of esophageal varices after outpatient endoscopic variceal ligation.

Objective:This study developed EVL as an outpatient technique and assessed recurrence of esophageal varices 12 months after initial eradication. Frequency of complications, rebleeding, hepatic transplantation and death were also studied. Methods:The population included patients with portal hypertension and esophageal varices, with endoscopy documented bleeding and not submitted to sclerotherapy. Eradication was defined as absence of varices upon insuflation of the esophagus or presence of grade I varices without red color sign. Recurrence was defined as the appearance of grade II or III varices in patients whose varices had been eradicated. An association with the following was searched: sex; age; etiology; Child-Pugh classification; variceal grading (I- IV); banding system; number of endoscopic sessions and number of rings. The associations between factors and outcomes were analyzed in terms of relative risk. Significance was determined using the chi-square or Fisher s exact test. Additional comparisons between quantitative variables were made using Student s t-test and Mann-Whitneys U-test. The effect of all factors under study was simultaneously evaluated by Cox s regression models.We also calculated Kaplan-Meyer s curves for variceal recurrence. Results:Fifty-five patients were studied (males = 41 or 74.5% ; medium age = 53.1 ± 13.44, range = 24-81 years) being 51 cirrhotics (Child-Pugh grade A = 22 or 43.1 %, grade B = 23 or 45.1 % and grade C = 6 or 11.7 % ) and 4 subjects with portal thrombosis without cirrhosis. Varices were invariably grade II or III and 48/55 (87%) had eradication after an average of 4.1 ± 1.88 sessions/per patient. Transitory complications (mild dysphagia and/or odynophagia) occurred in 16 individuals (29.1 %) but 1 had an esophageal perforation attributed to the endoscopic overtube. This patient recovered well after esophagorraphy. Rebleeding occurred in 5/55 (9.1 %) and hepatic transplant was carried on in 6/55 subjects(10.9%). Medium follow-up was 478 ± 347.85 days. In the 25 patients who had a followup greater than or equal to 12 months after eradication, esophageal varices recurred in eight (8/25 or 32 %). Mortality caused by EVL was zero but ten patients died of cirrhosis complications, without detectable digestive hemorrhage. Conclusions:Recurrence of varices after initial eradication is frequent after a follow-up period greater than or equal to 12 months.