Antônio Atalíbio Hartmann

p53 Immunohistochemical expression in Barrett's esophagus before and after endoscopic ablation by argon plasma coagulation

Objective. Few studies have evaluated p53 accumulation in the squamous mucosa contiguous (SMC) to Barretts esophagus (BE) and in the new squamous epithelium after endoscopic ablation. We evaluated the p53 expression in BE, in the SMC, and in the new squamous mucosa generated after ablation by argon plasma coagulation (APC). Material and methods. Endoscopic biopsy specimens from 37 BE patients, before and after ablation by APC, were analyzed. The p53 immunostaining criterion used was the staining of at least half of the nuclei. Results. p53 was detected in BE in 5 (13.5%) cases. In all these cases, SMC was p53(+). In addition, SMC was p53(–) in all cases of p53(–) BE (p<0.001). In the 5 cases with p53(+) BE and SMC, the new squamous mucosa continued to be p53(+). However, in the 32 cases with p53(–) SMC, the new squamous mucosa was also p53(–) (p<0.001). No case with p53(+) SMC turned out to be p53(–) after ablation. Similarly, no case with p53(–) BE and SMC before eradication became p53(+) after ablation (p<0.001). Conclusions. p53 was highly prevalent in the contiguous squamous mucosa when it is present in BE. After ablation, none of the cases lost p53 expression, and none of the negative cases turned out to be positive.

Cited Brazilian papers in general surgery between 1970 and 2009

OBJECTIVES To identify the most cited articles in general surgery published by Brazilian authors. INTRODUCTION There are several ways for the international community to recognize the quality of a scientific article. Although controversial, the most widely used and reliable methodology to identify the importance of an article is citation analysis. METHODS A search using the Institute for Scientific Information citation database (Science Citation Index Expanded) was performed to identify highly cited Brazilian papers published in twenty-six highly cited general surgery journals, selected based on their elevated impact factors, from 1970 to 2009. Further analysis was done on the 65 most-cited papers. RESULTS We identified 1,713 Brazilian articles, from which nine papers emerged as classics (more than 100 citations received). For the Brazilian contributions, a total increase of about 21-fold was evident between 1970 and 2009. Although several topics were covered, articles covering trauma, oncology and organ transplantation were the most cited. The majority of classic studies were done with international cooperation. CONCLUSIONS This study identified the most influential Brazilian articles published in internationally renowned general surgery journals.

Displasia no esôfago de Barrett - concordância intra e interobservador no diagnóstico histopatológico

BACKGROUNDnBarretts esophagus is a well-known pre-malignant condition. Pathologic interpretation of biopsy specimens guides endoscopic surveillance as well as the therapeutic approach that will be carried out. However, the predictive value of histopathologic diagnosis can be questioned due to its poor intra- and interobserver reproducibility.nnnAIMSnTo assess intra- and interobserver variability in the diagnosis of Barretts dysplasia.nnnMATERIAL AND METHODSnThree-micrometer thick sections from biopsy specimens from 42 patients with Barretts esophagus were stained with hematoxylin-eosin and PAS-alcian blue. The reading of the slides was carried out blindly in a light microscope. Intra and interobserver variability in the interpretation of the slides was determined by kappa statistics.nnnRESULTSnThe number of tissue specimens was 229, with average of 5.45 (1 to 18) fragments for patient. Low grade dysplasia was diagnosed by pathologists in 21.4% to 52.4% of the cases. The intra-observer agreement for the diagnosis of low grade dysplasia was slight (kappa = 0.30). The interobserver agreement for the diagnosis of low grade dysplasia was poor, with kappa scores between 0.05 and 0.16. The diagnosis of dysplasia, with agreement for all pathologists examining the same set of slides, was 14.3%.nnnCONCLUSIONSnPathologic interpretation of Barretts dysplasia may be subject to marked intra- and interobserver variabiliaty. Interpretation of low grade dysplasia, as high grade dysplasia, should also be considered for review by two or more pathologists.

Correlation between Alcian blue–periodic acid–Schiff stain and immunohistochemical expression of mucin 2 in Barrett's oesophagus

Sir: Barrett’s oesophagus (BO) is an acquired condition in which a length of the oesophageal squamous epithelium is replaced by a columnar epithelium containing goblet cells. It appears in up to 2% of the general population submitted to oesophagogastroduodenoscopy and 10% of patients with chronic symptoms of gastro-oesophageal reflux. The annual incidence of adenocarcinoma in this epithelium ranges between 0.2% and 2.1% in patients without dysplasia and up to 70% in those with high-grade dysplasia with a follow-up of 1–9 years. Therefore, an adequate diagnosis of BO is very important. In this regard, the Alcian blue– periodic acid–Schiff (AB–PAS) stain is helpful in the identification of intestinal metaplasia. Despite its usefulness, however, this technique is labourious, time-consuming, and more expensive than haematoxylin and eosin (H–E) staining. Indeed, AB–PAS may present difficulties of interpretation due to its heterogeneous staining. The biochemical marker of cellular differentiation mucin 2 (MUC-2) is able to identify intestinal metaplasia and represents a promising method for correlation with histopathological findings. We investigated whether MUC-2 is a good substitute for AB–PAS in the detection of goblet cells. Biopsy specimens from 40 BO patients were stained with H–E and AB–PAS. The expression of MUC-2 was evaluated by streptavidin–biotin peroxidase technique. The primary antibody was the mouse monoclonal antibody against MUC-2 (Ccp58; Novocastra Laboratories, Newcastle, UK). The secondary antibody was the antimouse rabbit of Dako LSAB 2 System kit (K0675; Dako Corp., Carpinteria, CA, USA). The chromogen used was DAB. Slide interpretation was carried out blindly by two examiners using a light microscope. The intraand interobserver agreements on the expression of MUC-2 in AB–PAS+ cases were determined by j statistics. MUC-2 showed expression in goblet cells and occasional expression in columnar cells, but was not expressed in either cardiac mucosa or in submucosal glands (Figure 1). There was full agreement between MUC-2 expression and staining of goblet cells by AB–PAS (Figure 2), with all patients showing a positive reaction with the use of either technique. In conclusion, MUC-2 expression turned out to be a helpful tool for the correct identification of intestinal metaplasia, avoiding any false-negatives or even false-positive results that may occur with the use of AB–PAS staining. These findings warrant the use of MUC-2 in the histopathological diagnosis of Barrett’s oesophagus.

O critério de positividade para a análise imunoistoquímica da p53 na confirmação da displasia do esôfago de Barrett faz diferença

BACKGROUNDnBarretts esophagus is the most serious complication of the gastroesophageal reflux disease and presents a malignant potential. The expression of the tumoral marker p53 increases with the dysplasia-adenocarcinoma sequence.nnnAIMSnTo evaluate the p53 expression in Barretts esophagus with or without dysplasia according to the two positive immunostaining criteria.nnnMATERIALS AND METHODSnThe material was constituted by endoscopic biopsy specimens from 42 patients with Barretts esophagus. Section of formalin-fixed and paraffin-embedded biopsies were stained with hematoxylin-eosin, PAS-alcian blue and evaluated the p53 immunohistochemical expression. Two p53 immunostaining criteria were utilized: 1. The staining of, at least, half of the nuclei, and 2. The staining of any nucleus. The diagnosis of dysplasia was confirmed by the agreement between three pathologists.nnnRESULTSnThe total number of tissue specimens was 229, with an average of 5.4 specimens per patient. Dysplasia, with agreement for all pathologists examining the same set of slides, was detected in six (14.3%) cases. According to the two different p53 immunostaining criteria, the protein was detected in non-dysplastic Barretts metaplasia, respectively, in 5 (13.9%) and 14 (38.9%) patients. Specifically in the six dysplastic cases, p53 was detected, according to the immunostaining criteria, in one (16.7%) and four (66.7%) cases, respectively.nnnCONCLUSIONSnIn this group, p53 immunohistochemical expression, regardless of positive criteria take into account, was not useful for detecting dysplasia in Barretts esophagus.BACKGROUND: Barretts esophagus is the most serious complication of the gastroesophageal reflux disease and presents a malignant potential. The expression of the tumoral marker p53 increases with the dysplasia-adenocarcinoma sequence. AIMS: To evaluate the p53 expression in Barretts esophagus with or without dysplasia according to the two positive immunostaining criteria. MATERIALS AND METHODS: The material was constituted by endoscopic biopsy specimens from 42 patients with Barretts esophagus. Section ectionss of formalinof formalin-fixed and paraffin-embedded biopsies were stained with hematoxylin-eosin, PAS-alcian blue and evaluated the p53 immunohistochemical expression. Two p53 immunostaining criteria were utilized: 1. the staining of, at least, half of the nuclei, and 2. the staining of any nucleus. The diagnosis of dysplasia was confirmed by the agreement between three pathologists. RESULTS: The total number of tissue specimens was 229, with an average of 5.4 specimens per patient. Dysplasia, with agreement for all pathologists examining the same set of slides, was detected in six (14.3%) cases. According to the two different p53 immunostaining criteria, the protein was detected in non-dysplastic Barretts metaplasia, respectively, in 5 (13.9%) and 14 (38.9%) patients. Specificaly in the six dysplastic cases, p53 was detected, according to the immunostaining criteria, in one (16.7%) and four (66.7%) cases, respectively. CONCLUSIONS: In this group, p53 immunohistochemical expression, regardless of positive criteria take into account, was not useful for detecting dysplasia in Barretts esophagus.

EUS-FNA WITH 19 OR 22 GAUGES NEEDLES FOR GASTRIC SUBEPITHELIAL LESIONS OF THE MUSCLE LAYER

ABSTRACT Background: Tissue diagnosis is required for gastric subepithelial lesions for differential diagnosis of GISTs. However, there has not been consensus about the best needle for EUS-guided sampling of these lesions. Aim: To evaluate the diagnostic yield of EUS-FNA for gastric subepithelial lesions of the proper muscle layer with large-bore 19 gauge needles. Methods: A prospectively maintained database was retrospectively reviewed to identify consecutive patients who underwent EUS-FNA with 19 and 22 gauge needles for gastric subepithelial lesions of the fourth endosonographic layer in a tertiary care referral center. EUS-FNA was performed by the same endosonographer, using the fanning technique, without on-site cytopathologist. Specimens were analysed through cell blocks by the same pathologist. Procedure results were categorized into diagnostic, defined as enough material for histopathology and immunohistochemistry, or nondiagnostic. Results: Eighty-nine patients (mean age: 59 years, 77% women) underwent 92 EUS-FNA with 19 (75) or 22 (17) gauge needles. Mean lesion size was 22.6 mm. Overall diagnostic yield was 88%. The diagnostic yield of 19 gauge was higher than that of 22 gauge needle (92%x70.6%; p=0.0410), and similar for lesions >2 cm and <2 cm (93.7%x90.7%; p=0.9563). The best performance for 19 gauge needles was obtained performing <3 needle passes. Complication rate was 2.8%. Conclusions: Diagnostic yield of EUS-FNA with 19 gauge needles is 92% for gastric subepithelial lesions of the proper muscle layer. It is safe and highly valuable for differentiation between GIST and leiomyoma, no matter the size of the lesion.

A relação do uso crônico de fenobarbital com áreas potencialmente pré-neoplásicas em fígado de ratos

BACKGROUNDnPhenobarbital has been used in experimental models because it is an important agent of carcinogenesis promotion in the liver of rats, and it is also non-genotoxic, organ-specific and dose-dependent.nnnAIMnTo evaluate the effects of the daily administration of phenobarbital in old rats treated with phenobarbital since their birth up to 24 months of age, in the absence of concomitant administration of chemical agents, which initiate carcinogenesis.nnnPATIENTS AND METHODSnA control group of male Wistar rats was fed with a basic diet and a second group was fed with the same basic diet added of 0.05% of phenobarbital, for a period of 24 months. Medium and right liver fragments were submitted to the histological processing and they were stained by hematoxiciline and eosin and were immunohystochemically colored to glutathione S-transferase placentary form.nnnRESULTSnGlutathione S-transferase placentary positive zones were detected in both groups and the images were analyzed concerning their number and surface extension through the technique of histometry analyses.nnnCONCLUSIONnChronic use of phenobarbital did not modify the number of glutathione S-transferase placentary form positive areas. Although, data indicates that glutathione S-transferase placentary form positive areas media size are increased, probably because there are an increase in their evolution capacity and irreversibility.

Differential diagnosis of mesenchymal neoplasms of the digestive tract by cell block and immunohistochemistry

To evaluate the diagnostic yield of the cell block (CB) technique with immunohistochemistry in patients with mesenchymal neoplasms of the gastrointestinal tract collected by endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA).

The role of linear endosonography for the diagnosis of acute pancreatitis when other methods failed

BACKGROUND AND STUDY AIMSnAcute pancreatitis has no obvious cause after clinical, laboratory and radiologic investigation in 10%-30% of patients, and the diagnosis of idiopathic pancreatitis is given. This study investigated the role of linear EUS for identification of possible causes for acute pancreatitis when other investigative methods failed.nnnPATIENTS AND METHODSnBetween June 2012 and March 2017, 35 patients [25 women; mean age: 51.9u2009+u200917.8 years] with idiopathic acute pancreatitis underwent linear EUS for investigation. All of these cases were contacted for a follow-up telephone interview to compare the EUS findings with the final diagnosis and outcome.nnnRESULTSnPancreaticobiliary abnormalities were identified in 19 of 35 (54.3%) patients. Ten (28.6%) patients had microlithiasis or biliary sludge. Microlithiasis and choledocholithiasis were identified in 8 (22.8%) and a single (2.8%) patient, respectively. Two patients presented gallbladder biliary sludge, one of them with microlithiasis. Chronic pancreatitis was found on EUS in 6 (17.1%) patients, and pseudotumoral masses confirmed by EUS-FNA as autoimmune pancreatitis were detected in other 3 (8.6%) cases. Linear EUS was normal in 13 (37.1%) patients, and demonstrated findings of recent acute pancreatitis but no other etiological factor in 3 (8.6%) cases. After a mean follow-up of 33.3 months, no case with a normal EUS evaluation presented a new episode of pancreatitis, 1 of 9 cases with microlithiasis presented an episode of recurrent pancreatitis due to choledocolithiasis after cholecystectomy, and 3 of 9 cases with chronic pancreatitis presented recurrent episodes, including the 2 cases of autoimmune pancreatitis.nnnCONCLUSIONSnLinear EUS provides diagnostic information in approximately a half of patients with idiopathic acute pancreatitis. Exclusion of pancreaticobiliary abnormalities on EUS has an important prognostic value for absence of new episodes of acute pancreatitis.

Bouveret syndrome and pancreatic acinar cell carcinoma

Bouveret syndrome and pancreatic acinar cell carcinoma are two rare conditions of the gastrointestinal tract [1–4]. Herein, we present a case in which both conditions occurred in the same patient. A 77-year-old man with diabetes and a history of cholelithiasis with recurrent episodes of biliary pain was referred for evaluation of epigastric pain, anorexia, nausea, bloating, and weight loss during the previous 6 weeks. Results of laboratory tests were normal. Magnetic resonance imaging demonstrated a solid lesion in the pancreatic head, and the patient was sent for evaluation with endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). Unexpectedly, at the beginning of the procedure, a huge hard gallstone was found to be completely obstructing the pylorus, and was impacted in the first portion of the duodenum. The stone was pulled back into the stomach using a polypectomy snare, and was broken into small fragments with a metal lithotriptor. The small fragments were still too large to be removed via the mouth, as they impacted below the cardia, and were therefore left in the stomach. The patient was asymptomatic, and a small-bowel contrast radiogram some days later confirmed the elimination of the stones. After the removal of the pyloric gallstone, EUS-FNA was performed through de duodenum. A nodule with regular margins and some small cystic areas, measuring 2.4 ×1.8 cm, was found in the head of the pancreas. FNA was performed using a 22-gauge needle, with a total of four passes, and the aspirated material was prepared as cell blocks. Histopathological evaluation and immunohistochemical panel for acinar-specific markers confirmed the diagnosis of an acinar cell carcinoma of the pancreas. Immunohistochemistry was positive for alpha-1-antichymotrypsin, alpha-1-trypsin, and CKM (AE1/AE3/PCK26). In addition, Ki-67 revealed a proliferation index of 70%. VIDEO 1