Esophageal achalasia secondary to mesothelioma

Summary Achalasia secondary to malignancy is rare, with most cases associated with gastric adenocarcinoma of the gastroesophageal junction. This report describes the clinicopathologic features of a 64-year-old man found to have mesothelioma as the cause of secondary achalasia. To our knowledge, this is the first case of secondary achalasia produced by a mesothelioma. We reviewed the English literature in regard to achalasia induced by tumors.This work was supported by the Veterans Administration.     

Esophageal adenocarcinoma developing above an Angelchik prosthesis

The Angelchik device is a horseshoe-shaped prosthesis made of silicone elastomer; it was inserted by the trans-abdominal route to encircle the lower esophagus and was used in the treatment of gastro-esophageal reflux disease. Over 25 000 were inserted worldwide, with acceptable symptom control in between 54% and 95% of patients. However, they were associated with a wide variety of complications, including intractable dysphagia, prosthesis migration and erosion into the stomach, and a significant proportion had to be removed. This article details the cases of three patients in our institution who underwent the insertion of an Angelchik prosthesis and who subsequently developed adenocarcinoma of the esophagus. It is suggested that the Angelchik prosthesis does not effectively prevent acid reflux and thus has no effect in preventing the dysplasia-metaplasia-adenocarcinoma sequence in the lower esophagus.     

Barrett食管与贲门癌

贲门癌的发病率逐年升高.由于贲门癌与食管腺癌流行病学特征相似,且Barrett食管已证实是食管腺癌的癌前病变,所以贲门癌的发生是否与Barrett食管有关成为目前研究的热点.本文就贲门癌研究现状及其与Barrett食管的相关性作一述评.     

Gastric and intestinal differentiation in Barrett''s metaplasia and associated adenocarcinoma

Intestinal metaplasia is a prerequisite criterion for the diagnosis of Barrett's metaplasia and the sole columnar esophageal lining associated with malignancy. It is recognized by the presence of goblet cells, but columnar non-goblet elements, producing gastric or intestinal proteins, are the prevalent cell population. The cellular heterogeneity of Barrett's metaplasia is well documented but the relationship between the distinct cell subtypes and neoplasia is unclear. Our aim was to clarify the relationship between the different metaplastic populations and malignancy in order to investigate putative markers for risk stratification of Barrett's patients. We studied 46 columnar-lined esophageal segments, 15 with associated adenocarcinoma. The presence of the gastric, MUC5AC and MUC6, and the intestinal, MUC2, proteins was evaluated in metaplastic (columnar and goblet) and neoplastic cells. In neoplasia MUC5AC and MUC6 were detected in 100% and 86.6% of the cases, respectively. In metaplasia there were no differences in MUC5AC and MUC6 immunoreactivity, between cases with and without associated neoplasia, except for goblet elements producing MUC6 that were exclusive of metaplasia adjacent to adenocarcinoma (P < 0.05). MUC2 was present in 86.6% of the neoplasia. In metaplasia it was restricted to Barrett's cases and was more frequent in areas with intestinal metaplasia. Columnar-lined esophagus without intestinal metaplasia did not express MUC2. Our study suggests a relationship between the metaplastic population with gastric phenotype and malignancy, and points to the involvement of columnar as well as goblet elements in tumorigenesis. The association between goblet cells aberrantly producing MUC6 and the presence of neoplasia suggests they may be useful for risk stratification.     

Barrett's esophagus: Macroscopic markers and the prediction of dysplasia and adenocarcinoma

BACKGROUND AND AIMS: Surveillance endoscopy has been advocated for patients with Barrett's esophagus but the cost-effectiveness of this has been questioned. The aim of this study is to identify an optimum surveillance protocol by examining if macroscopic markers at diagnosis predict the development of dysplasia. METHODS: The sample was 353 patients with Barrett's esophagus undergoing surveillance by a community-based group of gastroenterologists between 1981 and 2001. At diagnosis the presence of macroscopic and microscopic markers was noted. The presence and pattern of dysplasia and development of adenocarcinoma was documented during subsequent surveillance. RESULTS: Three hundred and fifty-three patients (71% male) underwent regular surveillance over 19 056 patient-months (median 42 months), having a median number of three surveillance endoscopies (range 1-40). Nine patients (seven male) developed adenocarcinoma (1/176 patient years) and four male patients developed high-grade dysplasia (1/397 patient years). Twelve of these 13 patients entered with one or more macroscopic markers: severe esophagitis, nodularity, Barrett's ulcer or stricture. Dysplasia risk was associated with macroscopic markers. Patients who entered with one marker were 6.7 times more likely to develop high-grade dysplasia/adenocarcinoma (HR = 6.7, 95% CI = 1.3, 35). Patients who entered with two or more markers were 14 times more likely to develop high-grade dysplasia/adenocarcinoma (HR = 14.1, 95% CI = 2.02, 102). CONCLUSIONS: The presence of severe esophagitis, Barrett's ulcer, nodularity or stricture at entry indicates a high-risk group for Barrett's esophagus. Cost-effectiveness of surveillance for these patients and those with dysplasia at entry would thus improve.     

Gene expression in rats with Barrett＇s esophagus and esophageal adenocarcinoma induced by gastroduodenoesophageal reflux

AIM: To study the different gene expression profiles in rats with Barrett's esophagus (BE) and esophageal adenocarcinoma (EA) induced by gastro-duodeno-esophageal reflux. METHODS: Esophagoduodenostomy was performed in 8-wk old Sprague-Dawley rats to induce gastro-duodeno-esophageal reflux, and a group of rats that received sham operation served as control. Esophageal epithelial pathological tissues were dissected and frozen in liquid nitrogen immediately. The expression profiles of 4 096 genes in EA and BE tissues were compared to normal esophagus epithelium in normal control (NC) by cDNA microarray. RESULTS: Four hundred and forty-eight genes in BE were more than three times different from those in NC, including 312 upregulated and 136 downregulated genes. Three hundred and seventy-seven genes in EA were more than three times different from those in NC, including 255 upregulated and 142 downregulated genes. Compared to BE, there were 122 upregulated and 156 downregulated genes in EA. In the present study, the interested genes were those involved in carcinogenesis. Among them, the upregulated genes included cathepsin C, aminopeptidase M, arachidonic acid epoxygenase, tryptophan-2,3-dioxygenase, ubiquitin-conjugating enzyme, cyclic GMP-stimulated phosphodiesterase, tissue inhibitor of metalloproteinase-1, betaine-homocysteine methyltra nsferase, lysozyme, complement 4b binding protein, complement 9 protein, insulin-like growth factor binding protein, UDP-glucuronosyltransferase, tissue inhibitor of metalloproteinase-3, aldolase B, retinoid X receptor gamma, carboxylesterase and testicular cell adhesion molecule 1. The downregulated genes included glutathione synthetase, lecithin-cholesterol acyltransferase, p55CDC, heart fatty acid binding protein, cell adhesion regulator and endothelial cell selectin ligand. CONCLUSION: Esophageal epithelium exposed excessively to harmful ingredients of duodenal and gastric reflux may develop into BE and even EA gradually. The gene expression level is different between EA and BE, and may be related to the occurrence and progression of EA.     

Endoscopic findings of adenocarcinoma arising from short-segment Barrett's esophagus

Adenocarcinoma arising from short-segment Barrett's esophagus (SSBE) is rare in Japan, although the incidence of this condition is increasing in Western countries. Four cases of early adenocarcinoma arising from SSBE were diagnosed and treated at Niigata-prefectural Yoshida Hospital. All patients were male, variously 55, 71, 73 and 79 years of age. All four patients had long-term gastroesophageal reflux disease, although one patient had erosive esophagitis and three patients did not have erosive esophagitis. Three patients were diagnosed as having Helicobacter pylori-free stomach. All adenocarcinomas occurred close to the squamocolumnar junction. Patients with SSBE should undergo detailed endoscopic examination of the squamocolumnar junction in order to detect early adenocarcinoma arising from SSBE.     

Prevalence of Barrett's esophagus and expression of mucin antigens detected by a panel of monoclonal antibodies in Barrett's esophagus and esophageal adenocarcinoma in Japan

Barrett's esophagus (BE) is an acquired disorder associated with a high incidence of adenocarcinoma of the lower esophagus. Moreover, it has been reported that short-segment BE may be associated with adenocarcinoma of the esophagogastric junction. The objective of this study was to define the prevalence of BE and the mucin profile in BE, including the short-segment type, and to compare the mucin profile in BE with the profiles of Barrett's adenocarcinoma and distal esophageal adenocarcinoma among Japanese. In total, 650 adult subjects underwent endoscopic examination for evaluation of BE. Although the prevalence of traditional (long segment) BE was 0.62%, the overall prevalence of BE including short-segment type was 15.7%. In Barrett's epithelium, the short-segment type predominantly had gastric type mucin, while the middle- and long-segment types possessed intestinal mucin, especially colonic type mucin (sulfo-Lewis^a), with high frequency. In Barrett's epithelium with adenocarcinoma, all Barrett's epithelium adjacent to carcinomas showed a predominance of immunoreactivity to sulfo-Lewis^a. In Barrett's adenocarcinomas, colonic type mucin was detected in 100% by monoclonal antibody (MoAb) 91.9H. Small-intestinal mucin and gastric mucin were stained in 50% and 12.5% of the subjects, respectively. Colonic type mucin was also detected with high frequency (80%) in distal esophageal adenocarcinomas without Barrett's epithelium. These data suggest that the epitope, not of small-intestinal type or gastric type mucin, but of colonic type mucin (sulfo-Lewis^a), may be associated with, at least in part, the malignant phenotype of BE. Received: July 28, 1999 / Accepted: February 25, 2000     

Esophageal cancer screening in achalasia: is there a consensus?

Achalasia is an important but relatively uncommon disorder. While highly effective therapeutic options exist, esophageal cancer remains a long‐term potential complication. The risk of esophageal cancer in achalasia remains unclear, with current guidelines recommending against routine endoscopic screening. However, given limited data and conflicting opinion, it is unknown whether consensus regarding screening practices in achalasia among experts exists. A 10‐question survey to assess screening practices in achalasia was created and distributed to 28 experts in the area of achalasia. Experts were identified based on publications and meeting presentations in the field. Survey responses were received from 17 of 28 (61%) experts. Wide geographic distribution was seen among respondents, with eight (47%) from Europe or Australia, seven (41%) from the United States, and two (12%) from Asia. Screening for esophageal cancer was inconsistent, with nine (53%) experts endorsing the practice and eight (47%) not. Screening practices did not differ among geographic regions. No consensus regarding the risk for esophageal cancer in achalasia was seen, with three experts reporting no increased risk compared with the general population, eight experts a lifetime risk of 0.1–0.5%, three experts a 0.5–1% risk, two experts a 1–2% risk, and one expert a 3–5% risk. However, these differences in perception of risk did not influence screening practices. Upper endoscopy was utilized among all experts who endorsed screening. However, practices still varied with screening commencing at or within 1 year of diagnosis in two practices compared with 5 and 10 years in three respective practices each. Surveillance intervals also varied, performed every 2 years in four practices, every 3 years in four practices, and every 5 years in one practice. Practice variation in the management of achalasia itself was also seen, with initial treatment with Heller myotomy endorsed by eight experts, pneumatic dilation by five experts, and two each endorsing peroral endoscopic myotomy or no specific preference. In addition, while 82% (14/17) of experts endorsed long‐term follow up of patients, no consensus regarding long‐term follow up existed, with annual follow up in eight practices, every 3–6 months in three practices, and every 2 years in three practices. Large practice variation in the long‐term management of achalasia exists among experts in the field. Only a slight majority of experts endorse screening for esophageal cancer in achalasia, and no consensus exists regarding how surveillance should be structured even among this group. Interestingly, the lack of consensus on cancer screening parallels a lack of agreement on initial treatment of achalasia. These findings suggest a need for greater homogeneity in the management of longstanding achalasia and cancer screening. Further, this study highlights the need for more data on this topic to foster greater agreement.     

Ethanolamine oleate as a novel therapy is effective in resistant idiopathic achalasia

Idiopathic achalasia (IA) is a primary motor disorder of the esophagus. Recently, ethanolamine oleate (EO) has been introduced as a novel therapy in IA. We investigate the long‐term efficacy of EO injection in the selected IA patients. Two hundred twenty patients with IA were evaluated prospectively. Thirty‐one patients who were resistant to or poor candidate of pneumatic balloon dilation and/or cardiomyotomy were enrolled in this study. EO was injected into the lower esophageal sphincter three times at 2‐week intervals. Patients were evaluated with the achalasia symptom score (ASS), timed barium esophagogram, and manometry before and after the injections. A good response was defined as a greater than 50% reduction from baseline in the ASS, height and/or volume of barium in TBE, and absence of severe dysphagia or regurgitation at 1.5 months after the last injection. Relapse was defined as two or more points increase in dysphagia score after an initial good response. The mean age of patients was 49.32 ± 19.3 years. Twenty‐nine patients had a good response and two had a poor response. The mean ASS decreased from 12.48 (±2.06) to 4.50 (±2.96) (P = 0.0001), and the mean volume of barium decreased from 115.35 (±93.40) to 45.50 (±60.86) mL at 1.5 months after the last injection (P = 0.0001).The mean lower esophageal sphincter pressure was 30.47 ± 13.95 before the treatment and decreased to 14.30 ± 11.89 at 1.5 months after the treatment. (P = 0.0001). The mean duration of follow up was 30.16 ± 11.3 (18–68) months. Twelve patients in whom symptoms relapsed were treated effectively with reinjection. In some patients, minor complications (chest pain and erosion in the distal esophagus) occurred. This study indicates that EO has a long‐term effect and can be considered for use in the selected IA patients.     

Progression of Barrett's mucosa to adenocarcinoma after antireflux surgery: Radiologic-pathologic correlation

A patient with Barrett's esophagus progressed to adenocarcinoma, despite antireflux operation, adequate medical therapy, and regular yearly surveillance by esophageal function tests and endoscopic biopsy. This case stresses the need for closer follow-up of patients with Barrett's esophagus even after adequate control of gastroesophageal reflux by anti-reflux surgery.     

Remission of arthritis after esophagectomy in three patients with severe achalasia

In the 1960s and 1970s, intestinal bypass surgery was performed to treat patients with extreme obesity. However, this is now done with great restriction due to the risk of complications, for instance, polyarthritis. An association between severe achalasia and arthritis has also been described, but very few articles on this topic are cited in PubMed, and most of the published case reports are old. In this article, we present a retrospective case series of three patients with severe achalasia and arthritis from the departments of rheumatology and surgery at a university hospital. The complaints from the esophagus as well as arthritis were resolved after esophagectomy and esophageal reconstruction. We conclude that severe achalasia can be associated with arthritis, and both can be cured by esophageal reconstruction. Thus, we want to remind of this rare, but probably largely unrecognized, association between achalasia and joint disease.     

Barrett's Surveillance Identifies Patients with Early Esophageal Adenocarcinoma

Background

Barrett's surveillance for dysplasia is recommended, but few studies have documented the benefit of endoscopic surveillance for dysplasia or cancer.

Objectives

Using a retrospective study design, we aim to demonstrate the impact of a Barrett's surveillance program on the stage of esophageal adenocarcinoma and identify factors for progression of metaplasia to cancer.

Subjects

The Institutional Review Board at Veterans Affairs Connecticut Healthcare approved the study. We report a retrospective review of a prospectively followed Barrett's cohort in a surveillance program and compared their outcome with patients with a new diagnosis of esophageal adenocarcinoma, identified at the same center between 1999 and 2005.

Results

There were 248 patients with Barrett's esophagus entered into a surveillance program from 1999 to 2005. During the surveillance period of 987 patient-years, 5 (0.5% patient-year) patients developed esophageal adenocarcinoma. During the same period, 46 patients were diagnosed with new-onset esophageal adenocarcinoma outside of our surveillance program. Only 5% of these patients had a history of gastroesophageal reflux disease. There were 248 patients who underwent a mean number of 2.7 ± 1.7 upper endoscopic procedures, with 26 (10%) patients developing dysplasia. Compared with nonsurveillance, more patients had early stage of cancer in the surveillance group (P <.001). All 5 patients with cancer diagnosed from Barrett's esophagus surveillance endoscopy were alive, compared with 20 of 46 (43%) patients with cancer diagnosed outside of the surveillance program. The length of Barrett's segment >3 cm was found to be associated with development of dysplasia, P = .004 (odds ratio 1.2; 95% confidence interval, 1.07-1.34).

Conclusion

Patients with Barrett's esophagus undergoing endoscopic surveillance benefit from early-stage cancer diagnosis. Progression to adenocarcinoma is low, but long-segment and high-grade dysplasias have an increased risk of cancer. A significant number of patients with newly diagnosed esophageal adenocarcinoma do not complain of gastroesophageal reflux disease and are therefore not investigated for Barrett's esophagus nor entered into surveillance. Patients and physicians can use this information in making a decision about surveillance.     

Superoxide dismutase prevents development of adenocarcinoma in a rat model of Barrett＇s esophagus

AIM: To test whether antioxidant treatment could prevent the progression of Barrett's esophagus to adenocarcinoma. METHODS: In a rat model of gastroduodenoesophageal reflux by esophagojejunal anastomosis with gastric preservation, groups of 6-10 rats were randomized to receive treatment with superoxide dismutase (SOD) or vehicle and followed up for 4 mo. Rat's esophagus was assessed by histological analysis, superoxide anion and peroxinitrite generation, SOD levels and DNA oxidative damage. RESULTS: All rats undergoing esophagojejunostomy developed extensive esophageal mucosal ulceration and inflammation by mo 4. The process was associated with a progressive presence of intestinal metaplasia beyond the anastomotic area (9% 1st mo and 50% 4th mo) (94% at the anastomotic level) and adenocarcinoma (11% 1st mo and 60% 4th mo). These changes were associated with superoxide anion and peroxinitrite mucosal generation, an early and significant increase of DNA oxidative damage and a significant decrease in SOD levels (P<0.05). Exogenous administration of SOD decreased mucosal superoxide levels, increased mucosal SOD levels and reduced the risk of developing intestinal metaplasia beyond the anastomotic area (odds ratio = 0.326; 95%CI: 0.108-0.981; P = 0.046), and esophageal adenocarcinoma (odds ratio = 0.243; 95%CI: 0.073-0.804; P = 0.021). CONCLUSION: Superoxide dismutase prevents the progression of esophagitis to Barrett's esophagus and adenocarcinoma in this rat model of gastrointestinal reflux, supporting a role of antioxidants in the chemoprevention of esophageal adenocarcinoma.     

Treatment of achalasia: lessons learned with Chagas' disease

SUMMARY.  Chagas' disease (CD) is highly prevalent in South America. Brazilian surgeons and gastroenterologists gained valuable experience in the treatment of CD esophagopathy (chagasic achalasia) due to the high number of cases treated. The authors reviewed the lessons learned with the treatment of achalasia by different centers experienced in the treatment of Chagas' disease. Preoperative evaluation, endoscopic treatment (forceful dilatation and botulinum toxin injection), Heller's myotomy, esophagectomy, conservative techniques other than myotomy, and reoperations are discussed in the light of personal experiences and review of International and Brazilian literature. Aspects not frequently adopted by North American and European surgeons are emphasized. The review shows that nonadvanced achalasia is frequently treated by Heller's myotomy. Endoscopic treatment is reserved to limited cases. Treatment for end-stage achalasia is not unanimous. Esophagectomy was a popular treatment in advanced disease; however, the morbidity/mortality associated to the procedure made some authors seek different alternatives, such as Heller's myotomy and cardioplasties. Minimally invasive approach to esophageal resection may change this concept, although few centers perform the procedure routinely.     

COX-2在Barrett食管和食管腺癌中的表达及意义

目的:探讨环氧合酶-2(COX-2)及其催化产生的前列腺素E2(PGE2)与Barrett食管及食管腺癌的关系．方法:采用RT-PCR、免疫组化和RIA等方法,分别测定Barrett食管组(n=16),食管腺癌组(n=17)和正常对照组(n=20)食管黏膜中COX-2 mRNA的表达率、 COX-2蛋白在组织中的表达率和在细胞中的分布情况,以及PGE2在组织中的含量．结果:87．50％(14／16)的Barrett食管和88．24％(15／17) 的食管腺癌中COX-2 mRNA呈阳性表达,与对照组 25．00％(5／20)比较均有显著差异(P<0．01)．免疫组织化学研究显示:COX-2蛋白在Barrett食管上皮细胞和食管腺癌的癌细胞细胞质中呈阳性表达,81．25％(13／16) 的Barrett食管和76．47％(13／17)的食管腺癌中COX-2 蛋白呈阳性表达,与对照组20．00％(4／20)比较均有显著差异(P<0．01),但Barrett食管组和食管腺癌组 COX-2蛋白表达率之间无显著差异(P>0．05)．放射免疫分析测定显示:Barrett食管组(541．41±34．30 ng／g)和食管腺癌组(559．224±37．77 ng／g)中PGE2的含量与对照组(357．10±37．58 ng／g)相比均有显著差异 (P<0．05),Barrett食管组和食管腺癌组之间PGE2的含量无显著差异(P>0．05)．结论:COX-2及其mRNA蛋白在Barrett食管和食管腺癌中均呈高表达．PGE2的含量在Barrett食管和食管腺癌中均增高．COX-2及其催化产生的PGE2可能与 Barrett食管及食管腺癌的形成有关．     

Characteristics of patients with columnar-lined Barrett＇s esophagus and risk factors for progression to esophageal adenocarcinoma

AIM: To determine the risk factors for the development of esophageal adenocarcinoma in these patients with columnar-lined esophagus (CLE). METHODS: Data collected retrospectively on 597 consecutive patients diagnosed at endoscopy and histology to have CLE at Leeds General Infirmary between 1984 and 1995 were analyzed. Factors evaluated included age, sex, length of columnar segment, smoking, and drinking habits, history of non-steroidal ingestion, presence of endoscopic esophagitis, ulceration or benign strictures and presence of Helicobacter pylori in esophageal biopsies. Univariate and multivariate analyses were performed to identify risk factors for the development of adenocarcinoma. RESULTS: Forty-four patients presented or developed esophageal adenocarcinoma during follow-up. Independent risk factors for the development of adenocarcinoma in patients with CLE were males (OR 5.12, 95%CI 2.04-12.84, P = 0.0005), and benign esophageal stricture (OR 4.37, 95%CI 2.02-9.45, P = 0.0002). Male subjects and patients who developed benign esophageal stricture constituted 86% (n = 38) of all patients who presented or developed esophageal adenocarcinoma. The presence of esophagitis was associated with a significant reduction in the development of esophageal carcinoma (OR 0.28, 95%CI 0.13-0.57, P = 0.0006). No other clinical characteristics differentiate between the non-malignant and malignant group. CONCLUSION: In patients with CLE, endoscopic surveillance for the early detection of adenocarcinoma may be restricted to male subjects, as well as patients who develop benign esophageal strictures.     

Association of ablation of Barrett''s esophagus with high grade dysplasia and adenocarcinoma of the gastric cardia

There has been increasing application of endoscopic ablation therapy for patients with high-grade dysplasia (HGD) and Barrett's esophagus (BE). Three cases are reported in which the patient developed adenocarcinoma of the gastric cardia after thermal ablation of HGD. A definition of BE including endoscopic abnormality and intestinal metaplasia by biopsy was used. Strict and standardized criteria were utilized for the endoscopic landmarks. Three cases are reported with long-segment BE and a nodule or mass in the endoscopic cardia post-thermal ablation. Biopsies documented adenocarcinoma of the gastric cardia. The development of adenocarcinoma of the cardia is unexpected. Speculation is offered as to the potential of increased proliferation and mutations at the new squamocolumnar interface after endoscopic ablation therapy to explain this association.