Sergio Szachnowicz

Origin of adenocarcinoma in Barrett's esophagus: P53 and Ki67 expression and histopathologic background

UNLABELLED Barretts esophagus is the substitution of squamous epithelium of the distal esophagus by columnar epithelium. Intestinal metaplasia in Barretts esophagus is considered to be the main risk factor for the development of adenocarcinoma. Diffuse adenocarcinoma and Barretts esophagus without intestinal metaplasia are rare, and reports on the subject are scarce. PURPOSE AND METHOD To estimate the prevalence of adenocarcinoma in 297 patients with Barretts esophagus, during the period of 1990 to 2002, and in 13 patients undergoing surgery, to conduct detailed macroscopic and microscopic analysis, with performance of immunohistochemical tests for p53 and Ki67, correlating the type of tumor with its adjacent epithelium. RESULTS In our patients with Barretts esophagus, there was a prevalence of 5.7% of adenocarcinoma. The tumors developed only when the Barretts esophagus segment was long (>3.0 cm). Tumors were located close to the squamous-columnar junction. The histological study revealed 2 patients (15.4%) with Barretts esophagus adjacent to a tumor with gastric metaplasia without the presence of intestinal metaplasia. Tumors were classified according to Nakamuras classification (23% differentiated pattern, and 77% undifferentiated pattern) and to Laurens classification (61% intestinal and 39% diffuse). The difference is due to the migration of microtubular and foveolar tumors of undifferentiated (gastric) pattern in Nakamuras classification to the Laurens intestinal type. The immunohistochemical test for Ki67 was strongly positive in all the patients, thus evidencing intense cell proliferation in both the columnar epithelium and tumor. Expression of p53 was negative in 67% of the adjacent columnar epithelia and 42% of the tumors, without any correlation between the tissue types. CONCLUSION Adenocarcinoma develops from mixed columnar epithelium, either intestinal or gastric, showing both the gastric and the intestinal patterns; thus, tumors can also grow in columnar epithelium without intestinal metaplasia. Barretts esophagus should be followed up for the possibility of progression to malignancy, especially when the segment is longer than 3 cm.

Anatomic study of gastric vascularization and its relationship to cervical gastroplasty

The aim of this study was to perform an anatomic study of the stomach and its vascularization, evaluating the frequency of communication between the right gastroepiploic artery (RGEA) and the left gastroepiploic artery (LGEA), as well as their relationship to the length of the stomach without extramural (direct) vascularization in cervical gastroplasty. Forty-two fresh human cadaveric specimens were studied, and the presence of communication between the RGEA and the LGEA was observed in 26 of the dissected stomachs (61.9%). When communication was present (group 1), to a total length of 49.60 cm of greater curvature length, it was verified that approximately 16.48 cm of this curvature lacked direct extramural vascularization (33.20%). When there was non-communication (group 2), to a greater curvature length of approximately 45.41 cm, it was found that 18.96 cm of this curvature (gastric fundus) lacked direct extramural vascular perfusion (41.76%). Results obtained in both groups were tested for statistically significant differences by the Pearson correlation test (P < 0.05). A P value of 0.05 or less was considered statistically significant. It can be concluded that the presence of communication between the RGEA and the LGEA increases extramural vascularization in the great gastric curvature.

Mucin pattern reflects the origin of the adenocarcinoma in Barrett's esophagus: a retrospective clinical and laboratorial study

BackgroundMucin immunoexpression in adenocarcinoma arising in Barretts esophagus (BE) may indicate the carcinogenesis pathway. The aim of this study was to evaluate resected specimens of adenocarcinoma in BE for the pattern of mucins and to correlate to the histologic classification.MethodsSpecimens were retrospectively collected from thirteen patients who underwent esophageal resection due to adenocarcinoma in BE. Sections were scored for the grade of intestinal metaplasia. The tissues were examined by immunohistochemistry for MUC2 and MUC5AC antibodies.ResultsEleven patients were men. The mean age was 61 years old (varied from 40 to 75 years old). The tumor size had a mean of 4.7 ± 2.3 cm, and the extension of BE had a mean of 7.7 ± 1.5 cm. Specialized epithelium with intestinal metaplasia was present in all adjacent mucosas. Immunohistochemistry for MUC2 showed immunoreactivity in goblet cells, while MUC5AC was extensively expressed in the columnar gastric cells, localizing to the surface epithelium and extending to a variable degree into the glandular structures in BE. Tumors were classified according to the mucins in gastric type in 7/13 (MUC5AC positive) and intestinal type in 4/13 (MUC2 positive). Two tumors did not express MUC2 or MUC5AC proteins. The pattern of mucin predominantly expressed in the adjacent epithelium was associated to the mucin expression profile in the tumors, p = 0.047.ConclusionBarretts esophagus adenocarcinoma shows either gastric or intestinal type pattern of mucin expression. The two types of tumors developed in Barretts esophagus may reflect the original cell type involved in the malignant transformation.

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.

Esophageal achalasia: a risk factor for carcinoma. A systematic review and meta-analysis

Achalasia of the cardia is associated with an increased risk of esophageal carcinoma. The real burden of achalasia at the malignancy genesis is still a controversial issue. Therefore, there are no generally accepted recommendations on follow-up evaluation for achalasia patients. This study aims to estimate the risk of esophageal adenocarcinoma and squamous cell carcinoma in achalasia patients. We searched for association between carcinoma and esophageal achalasia in databases up to January 2017 to perform a systematic review and meta-analysis. A total of 1,046 studies were identified from search strategy, of which 40 were selected for meta-analysis. A cumulative number of 11,978 esophageal achalasia patients were evaluated. The incidence of squamous cell carcinoma was 312.4 (StDev 429.16) cases per 100,000 patient-years at risk. The incidence of adenocarcinoma was 21.23 (StDev 31.6) cases per 100,000 patient-years at risk. The prevalence for esophageal carcinoma was 28 carcinoma cases in 1,000 esophageal achalasia patients (CI 95% 2, 39). The prevalence for squamous cell carcinoma was 26 cases in 1,000 achalasia patients (CI 95% 18, 39) and for adenocarcinoma was 4 cases in 1,000 achalasia patients (CI 95% 3, 6).The absolute risk increase for squamous cell carcinoma was 308.1 and for adenocarcinoma was 18.03 cases per 100,000 patients per year. To the best of our knowledge, this is the first meta-analysis estimating the burden of achalasia as an esophageal cancer risk factor. The high increased risk rate for cancer in achalasia patients points to a strict endoscopic surveillance for these patients. Also, the increased risk for developing adenocarcinoma in achalasia patients suggests fundoplication after myotomy, to avoid esophageal reflux and Barret esophagus, a known risk factor for adenocarcinoma.

Prevalence of gallstones in 1,229 patients submitted to surgical laparoscopic treatment of GERD and esophageal achalasia: associated cholecystectomy was a safe procedure

Background Association between esophageal achalasia/ gastroesophageal reflux disease (GERD) and cholelithiasis is not clear. Epidemiological data are controversial due to different methodologies applied, the regional differences and the number of patients involved. Results of concomitant cholecistectomy associated to surgical treatment of both diseases regarding safety is poorly understood. Aim To analyze the prevalence of cholelithiasis in patients with esophageal achalasia and gastroesophageal reflux submitted to cardiomyotomy or fundoplication. Also, to evaluate the safety of concomitant cholecistectomy. Methods Retrospective analysis of 1410 patients operated from 2000 to 2013. They were divided into two groups: patients with GERD submitted to laparocopic hiatoplasty plus Nissen fundoplication and patients with esophageal achalasia to laparoscopic cardiomyotomy plus partial fundoplication. It was collected epidemiological data, specific diagnosis and subgroups, the presence or absence of gallstones, surgical procedure, operative and clinical complications and mortality. All groups/subgroups were compared. Results From 1,229 patients with GERD or esophageal achalasia, submitted to laparoscopic cardiomyotomy or fundoplication, 138 (11.43%) had cholelitiasis, occurring more in females (2.38:1) with mean age of 50,27 years old. In 604 patients with GERD, 79 (13,08%) had cholelitiasis. Lower prevalence occurred in Barretts esophagus patients 7/105 (6.67%) (p=0.037). In 625 with esophageal achalasia, 59 (9.44%) had cholelitiasis, with no difference between chagasic and idiopathic forms (p=0.677). Complications of patients with or without cholecystectomy were similar in fundoplication and cardiomyotomy (p=0.78 and p=1.00).There was no mortality or complications related to cholecystectomy in this series. Conclusions Prevalence of cholelithiasis was higher in patients submitted to fundoplication (GERD). Patients with chagasic or idiopatic forms of achalasia had the same prevalence of cholelithiasis. Gallstones occurred more in GERD patients without Barretts esophagus. Simultaneous laparoscopic cholecystectomy was proved safe.

Adenocarcinoma of transposed colon: first case of synchronous tumor

Woman with 53-years-old diagnosed with congenital esophageal atresia, underwent to several surgical procedures in childhood, the latest was a cervical retrosternal esophagocoloplasty at 11 years old. After 42 years she was evolved with cervical dysphagia, and an initial diagnosis of stenosis of the esophagocolic anastomosis was performed, treated with endoscopic dilation without improvement. Later, biopsies were performed in the area of stenosis in proximal colonic segment (Figure 1) and polypectomy of sessile polyp of 10 mm, 5 cm distal to the stenosis (Figure 2). The pathological assessment showed tubular-villous intramucosal adenocarcinoma at the resected polyp and the area of stenosis was a invasive adenocarcinoma in colonic mucosa. Colonoscopy of remained colon was normal. Staging performed with CT scan showed an eccentric wall thickening of proximal colon transposed with luminal reduction target of left innominate vein; densification of mediastinal fat plane adjacent and regional lymph nodes up to 1.9 cm.

Heller-Pinotti, a modified partial fundoplication associated with myotomy to treat achalasia: technical and final results from 445 patients

Aim: The need for an antireflux procedure after myotomy is no longer as controversial as it used to be. However, the choice of the best fundoplication after myotomy is still controversial. The authors present the results of laparoscopic myotomies associated with postero-latero-anterior fundoplications (Heller-Pinotti). Methods: Medical records and endoscopic findings were reviewed for achalasia patients that had submitted to the procedure following 5 years of followup. Results: In total, 445 patients were enrolled: 39 (8.7%) presented erosive esophagitis, the Los Angeles classification being A-21, B-12, C-2 and D-4 (2 with peptic substenosis and 2 Barret); 41 (9.2%) patients had dysphagia, 4 needed reinterventions; 49 (11%) presented a migration of the fundoplication wrap to the thorax due to hiatal hernia, this was correlated with a higher risk of present erosive esophagitis (P = 0.047) and dysphagia (P < 0.001). Conclusion: Laparoscopy myotomy postero-latero-anterior fundoplication (Heller-Pinotti) produces a good long-term outcome for dealing with dysphagia and in terms of reflux prevention.

Avaliação de refluxo ultra-distal com pHmetria de múltiplos canais

RACIONAL: Displasia e adenocarcinoma esofagico surge em pacientes com esofago de Barrett submetidos a tratamento cirurgico (fundoplicatura) com pHmetria esofagica sem evidencia de acidez, o que sugere existir refluxo distal ao cateter de pHmetria convencional. OBJETIVO: Desenvolver metodologia para avaliar refluxo ultra-distal (1 cm acima da borda superior de esfincter inferior do esofago). METODO: Foram selecionados 11 pacientes com esofago de Barrett previamente submetidos a fundoplicatura a Nissen, sem sintomas de refluxo, com endoscopia e estudo contrastado de esofago sem sinais de recidiva. Foi realizada manometria esofagica para avaliar a localizacao e a extensao do esfincter esofagico inferior (EIE). Realizou-se entao pHmetria esofagica com quatro canais: canal A a 5 cm acima da borda superior do EIE; canal B a 1 cm acima; canal C intraesfincteriano; canal D intragastrico. Avaliou-se o escore de DeMeester no canal A. Comparou-se o numero de episodios de refluxo acido, o numero de episodios de refluxo prolongado e a fracao de tempo com pH<4,0 nos canais A e B. Comparou-se a fracao de tempo de pH<4,0 nos canais B e C. A fracao de tempo com pH<4,0 acima de 50% no canal D foi usada como parâmetro para nao migracao proximal do cateter. RESULTADOS: Houve aumento significativo do numero de episodios de refluxo e da fracao de tempo com pH<4,0 no canal B em relacao ao canal A. Houve reducao do tempo de pH<4,0 no canal B em comparacao ao canal C. Dois casos de adenocarcinoma esofagico foram diagnosticados nos pacientes do grupo estudado. CONCLUSOES: A regiao 1 cm acima da borda superior do EIE esta mais exposta a acidez do que a regiao 5 cm acima, embora em niveis reduzidos. A regiao 1 cm acima da borda superior do EIE esta menos exposta a acidez do que a regiao intraesfincteriana, demonstrando eficacia da fundoplicatura.

Novas perspectivas no estadiamento e tratamento do câncer de esôfago

BACKGROUND: The esophageal cancer presents as one of the most frequent and lethal neoplasia. Lymphatic involvement appears to be the principal individual factor for poor prognosis, thus esophagectomy with extensive lymphadenectomy still is the choice treatment. Thoracotomy for extensive resection is related to higher survival rate, as well as higher morbid-mortality rates. Micrometastasis concept involves a more accurate staging method for resected tumors, using immunohistochemistry or polymerase chain reaction techniques, which were not diagnosed by conventional methods. METHODS: A literature review was made over scientific articles published and available at PubMed site (www.pubmed.gov), crossing the following headings: esophageal neoplasm, molecular biology, neoplasm staging, sentinel lymph node, lymphatic metastasis. LITERATURE REVIEW: Sentinel lymph node concept consist of intraoperative identification of possible primary dissemination metastasis sites, thus guiding to a more complete and not so extensively lymphatic resection, decreasing morbid-mortality and restraining an over-dimensioned procedure that may not benefit the patient. CONCLUSION: Accurate staging by micrometastasis identification and precise treatment using sentinel lymph node method may bring new perspectives in the esophageal cancer treatment, especially on early-stages tumors.