Rubens Sallum

Evaluation of gene amplification and protein expression of HER-2/neu in esophageal squamous cell carcinoma using Fluorescence in situ Hybridization (FISH) and immunohistochemistry

BackgroundEsophageal squamous cell carcinoma (ESCC) is the sixth most frequent neoplasia in Brazil. It is usually associated with a poor prognosis because it is often at an advanced stage when diagnosed and there is a high frequency of lymph node metastases. It is important to know what prognostic factors can facilitate diagnosis, optimize therapeutic decisions, and improve the survival of these patients. A member of the epidermal growth factor receptor (EGFR) family, c-erbB-2, has received much attention because of its therapeutic implications; however, few studies involving fluorescence in situ hybridization (FISH) analysis of HER-2/neu gene amplification and protein expression in ESCC have been conducted. The aim of this study was to verify the presence of HER-2/neu gene amplification using FISH, and to correlate the results with immunohistochemical expression and clinical-pathological findings.MethodsOne hundred and ninety-nine ESCC cases were evaluated using the Tissue Microarray (TMA) technique. A polyclonal antibody against c-erbB-2 was used for immunohistochemistry. Analyses were based on the membrane staining pattern. The results were classified according to the Herceptest criteria (DAKO): negative (0/1+), potential positive (2+) and positive (3+). The FISH reactions were performed according to the FISH HER2 PharmDx (DAKO) protocol. In each case, 100 tumor nuclei were evaluated. Cases showing a gene/CEN17 fluorescence ratio ≥ 2 were considered positive for gene amplification.ResultsThe c-erbB-2 expression was negative in 117/185 cases (63.2%) and positive in 68 (36.8%), of which 56 (30.3%) were 2+ and 12 (6.5%) were 3+. No significant associations were found among protein expression, clinicopathological data and overall survival. Among the 47 cases analyzed, 38 (80.9%) showed no gene amplification while 9 (19.1%) showed amplification, as demonstrated by FISH. Cases that were negative (0/1+) and potential positive (2+) for c-erbB-2 expression by immunohistochemistry showed no gene amplification. However, all cases with gene amplification were positive (3+) by immunohistochemistry. According to univariate analysis, there was a significant difference (p = 0.003) in survival rates when cases with and without HER-2/neu amplification were compared.ConclusionOur data demonstrate the correspondence between gene amplification and protein expression of HER-2/neu. Gene amplification is an indicator of poor prognosis in ESCC.

Expression Profile of Malignant and Nonmalignant Lesions of Esophagus and Stomach: Differential Activity of Functional Modules Related to Inflammation and Lipid Metabolism

Adenocarcinomas of stomach and esophagus are frequently associated with preceding inflammatory alterations of the normal mucosa. Whereas intestinal metaplasia of the gastric mucosa is associated with higher risk of malignization, Barretts disease is a risk factor for adenocarcinoma of the esophagus. Barretts disease is characterized by the substitution of the squamous mucosa of the esophagus by a columnar tissue classified histopathologically as intestinal metaplasia. Using cDNA microarrays, we determined the expression profile of normal gastric and esophageal mucosa as well as intestinal metaplasia and adenocarcinomas from both organs. Data were explored to define functional alterations related to the transformation from squamous to columnar epithelium and the malignant transformation from intestinal metaplasia to adenocarcinomas. Based on their expression profile, adenocarcinomas of the esophagus showed stronger correlation with intestinal metaplasia of the stomach than with Barretts mucosa. Second, we identified two functional modules, lipid metabolism and cytokine, as being altered with higher statistical significance. Whereas the lipid metabolism module is active in samples representing intestinal metaplasia and inactive in adenocarcinomas, the cytokine module is inactive in samples representing normal esophagus and esophagitis. Using the concept of relevance networks, we determined the changes in linear correlation of genes pertaining to these two functional modules. Exploitation of the data presented herein will help in the precise molecular characterization of adenocarcinoma from the distal esophagus, avoiding the topographical and descriptive classification that is currently adopted, and help with the proper management of patients with Barretts disease.

Exposure of Splenic Hilum Increases Safety of Laparoscopic Splenectomy

Laparoscopic splenectomy is becoming the gold standard technique for the treatment of hematological disorders of the spleen. Hemostasis is a fundamental step during laparoscopic splenectomy leading some authors to develop several techniques to control splenic vessels such as hand assistance, preoperative splenic artery embolization, and the use of vascular linear staplers. However, intraoperative bleeding is usually due to inadequate exposure of the hilar splenic vessels itself. The authors describe a standardized technique for the exposure of splenic pedicle using an endoscopic triangular retractor. We have been used this technique in 16 consecutive laparoscopic splenectomies with minimal blood loss. The present technique may increase the safety of laparoscopic splenectomy with adequate exposure of the splenic hilum reducing the conversion rate and intraoperative blood loss.

Endobronchial Ultrasound Application for Diagnosis of Tracheobronchial Tree Invasion by Esophageal Cancer

INTRODUCTION: Esophageal cancer staging has been performed through bronchoscopy, computerized tomography (CT), positron emission tomography (PET), and endoscopic ultrasound (EUS). Whereas CT and PET scan provide assessments of distant metastasis, bronchoscopy importantly diagnoses tracheobronchial involvement, complementing chest CT findings. EUS is the most accurate examination for T and N staging but is technically limited when tumoral stenoses cannot be traversed. Endobronchial ultrasound (EBUS) appears to present greater accuracy than EUS, CT, and bronchoscopy for assessing tracheobronchial wall involvement. EBUS has been recently associated with EUS for esophageal cancer staging in our unit. OBJECTIVE: To compare EBUS findings in esophageal cancer patients without evident signs of tracheobronchial invasion on conventional bronchoscopy with EUS and CT. METHODS: Fourteen patients with esophageal cancer underwent CT, conventional bronchoscopy, EUS, and EBUS for preoperative staging. All patients underwent EBUS and EUS with an Olympus® MH-908 echoendoscope at 7.5 MHz. Seven patients were eligible for the study according to the inclusion criteria. RESULTS: The echoendoscope could not traverse tumoral esophageal stenosis to perform EUS in two patients, and invasion was effectively diagnosed by EBUS. In 4 (57%) of 7 patients EBUS revealed additional information to staging. In the remaining 3 cases the invasion findings were the same under both EUS and EBUS. CONCLUSION: EBUS showed signs of tracheobronchial invasion not observed by conventional bronchoscopy, adding information to staging in most of the cases when compared with CT and EUS.

Primary malignant melanoma of the esophagus: a rare and aggressive disease

Primary malignant melanoma of the esophagus is an uncommon tumor, with approximately 300 cases having been reported thus far. The purpose of this study was to describe a case of a 60 year-old man with a 10 month history of progressive dysphagia and thoracic pain, the investigations of which led to a diagnosis of primary malignant melanoma of the esophagus. The patient underwent a transhiatal esophagectomy with subcarinal lymphadenectomy, and isoperistaltic gastric tube replacement of the esophagus. Nine months after surgery, he developed ischemic colitis, and metastasis in the mesentery was diagnosed. His disease progressed and he died one year after the esophagectomy. A review of the literature was performed.

Endoscopic Detection of Early Esophageal Squamous Cell Carcinoma in Patients with Achalasia: Narrow-Band Imaging versus Lugol's Staining

Chromoendoscopy with Lugols staining remains the gold standard technique for detecting superficial SCC. An alternative technique, such as narrow-band imaging (NBI), for “optical staining” would be desirable, since NBI is a simpler technique and has no known complications. In this study, we compare NBI without magnification and chromoendoscopy with Lugols staining for detecting high-grade dysplasia and intramucosal esophageal squamous cell carcinoma (SCC) in patients with achalasia. This was a prospective observational study of 43 patients with achalasia referred to the Gastrointestinal Endoscopy Unit of the Hospital of Clinics, São Paulo, University Medical School, Brazil, from October 2006 to February 2007. Conventional examinations with white light, NBI, and Lugol staining were consecutively performed, and the suspected lesions were mapped, recorded, and sent for biopsy. The results of the three methods were compared regarding sensitivity, specificity, accuracy, positive predictive value, negative predictive value, positive likelihood value, and negative likelihood value. Of the 43 patients, one was diagnosed with esophageal squamous cell carcinoma, and it was detected by all of the methods. NBI technology without magnification has high sensitivity and negative predictive value for detecting superficial esophageal squamous cell carcinoma, and it has comparable results with those obtained with Lugols staining.

Comparative study of two modes of gastroesophageal reflux measuring: conventional esophageal pH monitoring and wireless pH monitoring

CONTEXT Esophageal pH monitoring is considered to be the gold standard for the diagnosis of gastroesophageal acid reflux. However, this method is very troublesome and considerably limits the patients routine activities. Wireless pH monitoring was developed to avoid these restrictions. OBJECTIVE To compare the first 24 hours of the conventional and wireless pH monitoring, positioned 3 cm above the lower esophageal sphincter, in relation to: the occurrence of relevant technical failures, the ability to detect reflux and the ability to correlate the clinical symptoms to reflux. METHODS Twenty-five patients referred for esophageal pH monitoring and with typical symptoms of gastroesophageal reflux disease were studied prospectively, underwent clinical interview, endoscopy, esophageal manometry and were submitted, with a simultaneous initial period, to 24-hour catheter pH monitoring and 48-hour wireless pH monitoring. RESULTS Early capsule detachment occurred in one (4%) case and there were no technical failures with the catheter pH monitoring (P = 0.463). Percentages of reflux time (total, upright and supine) were higher with the wireless pH monitoring (P < 0.05). Pathological gastroesophageal reflux occurred in 16 (64%) patients submitted to catheter and in 19 (76%) to the capsule (P = 0.355). The symptom index was positive in 12 (48%) patients with catheter pH monitoring and in 13 (52%) with wireless pH monitoring (P = 0.777). CONCLUSIONS 1) No significant differences were reported between the two methods of pH monitoring (capsule vs catheter), in regard to relevant technical failures; 2) Wireless pH monitoring detected higher percentages of reflux time than the conventional pH-metry; 3) The two methods of pH monitoring were comparable in diagnosis of pathological gastroesophageal reflux and comparable in correlating the clinical symptoms with the gastroesophageal reflux.

Pancreatectomia distal videolaparoscópica em pacientes com cistadenoma de pâncreas

BACKGROUND Cystic neoplasms are an uncommon group among pancreatic tumors. These lesions are seen more frequently in recent surgical practice, probably because of advances in diagnostic and surgical techniques. Total tumor resection provides the best chance of cure and may remove the risk of malignant transformation of the cystadenomas, particularly of the mucinous type. Minimally invasive techniques have been revolutionary and provide clinical evidence of decreased morbidity and comparable efficacy to traditional, open surgery. However, laparoscopic pancreatic resection is not an established treatment for tumors of the pancreas. AIM The authors present their initial experience with laparoscopic distal pancreatectomy for pancreatic cystadenomas. MATERIAL AND METHODS Three female patients (mean age, 55 years) underwent laparoscopic pancreatic resection between September 2001 and December 2003. RESULTS Laparoscopic pancreatic resection was successfully performed in all patients. Operative time varied between 4 and 6 hours. Intraoperative bleeding was minimal. Due to a thick pancreas, the application of vascular endoscopic stapler was difficult in one patient. Two patients presented postoperative pancreatic leakage with spontaneous resolution. CONCLUSIONS Resection of the pancreas can be safely performed via the laparoscopic approach with all the potential benefits to the patients of minimally invasive surgery.

Squamous cell carcinoma and neuroendocrine carcinoma colliding in the esophagus.

A collision tumor consists of two independent neoplasms growing in close proximity until they become juxtaposed, appearing as one lesion. This is a very rare situation with unclear physiopathology. Collision tumors should be distinguished from composite tumors, which consist of one neoplastic clone that diverges into two cell lineages. Collisions located in the esophagus are particularly uncommon.

Use of multiple channel pH monitoring for evaluation of ultra-distal reflux in patients after fundoplication for treatment of Barrett's esophagus.

Dysplasia and esophageal adenocarcinoma may arise in patients with Barretts esophagus after fundoplication esophageal pH monitoring showing no acid in esophagus. This suggests the need to develop methodology to evaluate the occurrence of ultra-distal reflux (1cm above the LES). The objective of the study was to compare acid exposition in three different levels: 5cm above the upper border of the LES, 1cm above the LES and in the intrasphincteric region. Eleven patients with Barretts esophagus after Nissen fundoplication with no clinical, endoscopic and radiologic evidence of reflux were selected. Four-channel pH monitoring took place: channel A, 5cm above the upper border of the LES; channel B, 1cm above the LES; channel C, intrasphincteric; channel D, intragastric. The results of channels A, B and C were compared. There was significant increase in number of reflux episodes and a higher fraction of time with pH <4.0 in channel B compared to channel A. There was significant decrease in fraction of time with pH <4.0 in channel B compared to channel C. Two cases of esophageal adenocarcinoma were diagnosed in the studied patients. The region 1cm above the upper border of the LES is more exposed to acid than the region 5cm above the upper border of the LES, although this exposure occurred in reduced levels. The region 1cm above the upper border of the LES is less exposed to acid than the intrasphincteric region.