Barrett’s esophagus and Barrett’s carcinoma

The alarming rise in the incidence of esophageal adenocarcinomas in the Western world has focused interest on so-called Barrett’s esophagus. Barrett’s esophagus is characterized by specialized intestinal epithelium replacing the normal squamous epithelium in the distal esophagus and is considered a consequence of long-lasting and severe gastroesophageal reflux disease. A metaplasia-dysplasia-carcinoma sequence links Barrett’s esophagus with adenocarcinoma of the distal esophagus (Barrett’s cancer). Despite intensive research, many questions concerning the pathogenesis, diagnosis, and treatment of Barrett’s esophagus and associated adenocarcinoma are still unanswered. Based on current data, the malignant progression of Barrett’s esophagus cannot be substantially prevented by medical or surgical therapy for reflux. Although no firm data are available to show that surveillance strategies can reduce overall mortality from Barrett’s cancer, early detection and cure are possible. Management of Barrett’s esophagus and carcinoma is reviewed with reference to the sequence of disease from metaplasia to carcinoma.     

Rathke’s cleft cysts: review of natural history and surgical outcomes

Rathke’s cleft cysts (RCCs), also known as pars intermedia cysts, represent benign lesions formed from remnants of the embryologic Rathke’s pouch. Commonly asymptomatic, they are identified in nearly 1 in 6 healthy volunteers undergoing brain imaging. When symptomatic, they can cause headaches, endocrine dysfunction, and, rarely, visual disturbances. A systematic review of the published English literature was performed focusing on large modern case series of RCCs to describe their natural history, clinicopathologic features, radiographic features, and surgical outcomes, including rates of recurrence. The natural history of asymptomatic RCCs is one of slow growth, suggesting that observation through serial magnetic resonance imaging is appropriate for smaller asymptomatic RCCs. Symptomatic RCCs can be treated by surgical resection with low morbidity, usually through an endonasal transsphenoidal corridor using either a microscope or an endoscope. Surgical treatment frequently provides symptomatic relief of headaches and visual disturbances, and sometimes even improves endocrine dysfunction. Rates of recurrence after surgical treatment range from 16 to 18 % in large series, and higher rates of recurrence are associated with suprasellar location, inflammation and reactive squamous metaplasia in the cyst wall, superinfection of the cyst, and use of a fat graft into the cyst cavity.     

Cigarette smoking and the risk of Barrett’s esophagus

Introduction  We examined the association between smoking and the risk of Barrett’s esophagus (BE), a metaplastic precursor to esophageal adenocarcinoma. Methods  We conducted a case–control study within the Kaiser Permanente Northern California population. Patients with a new diagnosis of BE (n = 320) were matched to persons with gastroesophageal reflux disease (GERD) (n = 316) and to population controls (n = 317). Information was collected using validated questionnaires from direct in-person interviews and electronic databases. Analyses used multivariate unconditional logistic regression that controlled for age, gender, race, and education. Results  Ever smoking status, smoking intensity (pack-years), and smoking cessation were not associated with the risk of BE. Stratified analyses suggested that ever smoking may be associated with an increased risk of BE among some groups (compared to population controls): persons with long-segment Barrett’s esophagus (odds ratio [OR] = 1.72, 95% confidence interval [CI] 1.12–2.63); subjects without GERD symptoms (OR = 3.98, 95% CI 1.58–10.0); obese subjects (OR = 3.38, 95% CI 1.46–7.82); and persons with a large abdominal circumference (OR = 3.02, 95% CI (1.18–2.75)). Conclusion  Smoking was not a strong or consistent risk factor for BE in a large community-based study, although associations may be present in some population subgroups.     

Treatment of Barrett’s esophagus with high-grade dysplasia

The incidence of esophageal adenocarcinoma is increasing in the USA, now accounting for at least 4% of US cancer-related deaths. Barrett’s esophagus is the main risk factor for the development of esophageal adenocarcinoma. The annual incidence of development of adenocarcinoma in Barrett’s esophagus is approximately 0.5% per year, representing at least a 30–40-fold increase in risk from the general population. High-grade dysplasia is known to be the most important risk factor for progression to adenocarcinoma. Traditionally, esophagectomy has been the standard treatment for Barrett’s esophagus with high-grade dysplasia. This practice is supported by studies revealing unexpected adenocarcinoma in 29–50% of esophageal resection specimens for high-grade dysplasia. In addition, esophagectomy employed prior to tumor invasion of the muscularis mucosa results in 5-year survival rates in excess of 80%. Although esophagectomy can result in improved survival rates for early-stage cancer, it is accompanied by significant morbidity and mortality. Recently, more accurate methods of surveillance and advances in endoscopic therapies have allowed scientists and clinicians to develop treatment strategies with lower morbidity for high-grade dysplasia. Early data suggests that carefully selected patients with high-grade dysplasia can be managed safely with endoscopic therapy, with outcomes comparable to surgery, but with less morbidity. This is an especially attractive approach for patients that either cannot tolerate or decline surgical esophagectomy. For patients that are surgical candidates, high-volume centers have demonstrated improved morbidity and mortality rates for esophagectomy. The addition of laparoscopic esophagectomy adds a less invasive surgical resection to the treatment armanentarium. Esophagectomy will remain the gold-standard treatment of Barrett’s esophagus with high-grade dysplasia until clinical research validates the role of endoscopic therapies. Current treatment strategies for Barrett’s esophagus with high-grade dysplasia will be reviewed.     

Iron intake and markers of iron status and risk of Barrett’s esophagus and esophageal adenocarcinoma

Objective  

To investigate the association between iron intake and iron status with Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC).     

Toenail selenium status and the risk of Barrett’s esophagus: the Netherlands Cohort Study

Objective  

To investigate the association between selenium and the risk of Barrett’s esophagus (BE), the precursor lesion of esophageal adenocarcinoma.     

Correlation between the gene expression profiles of adenocarcinoma of esophagus and Barrett＇s esophagus

Objective  

The aim of this study was to investigate the characteristics of gene changes from Barrett’s esophagus (BE) to esophageal adenocarcinoma by cDNA microarray.     

Dietary intake of vegetables, folate, and antioxidants and the risk of Barrett’s esophagus

Purpose

Diet is a potentially modifiable risk factor for Barrett’s esophagus (BE). We investigated the associations between intakes of fruits and vegetables and risk of BE.

Methods

We identified study subjects from 1,859 participants who underwent the endoscopy in a single VA Medical Center in the US between 2008 and 2011. Dietary intake in the previous year was elicited using a self-administered Block food frequency questionnaire (FFQ). Logistic regression model was used to estimate odds ratio (OR) and its 95 % confidence interval (CI) for BE.

Results

A total of 151 cases with definite BE and 777 controls completed the FFQ. When highest tertile of intake was compared with the lowest, the OR (95 % CI) was 0.46 (0.26–0.81) for dark green vegetables, 0.52 (0.30–0.90) for legumes, 0.50 (0.28–0.90) for total fiber, 0.45 (0.25–0.81) for isoflavones, 0.52 (0.30–0.67) for total folate, and 0.45 (0.26–0.79) for lutein, adjusting for multiple confounding factors including use of aspirin or proton pump inhibitor, gastro-esophageal reflux symptoms, and physical activity. The association for dark green vegetables was attenuated after adjustment for lutein, total fiber, and total folate (OR = 0.82; 95 % CI 0.30–2.22).

Conclusion

Higher intake of dark green vegetables was associated with a decreased risk of BE in a veteran population. Such an inverse association may be partially mediated by lutein, fiber, and folate. The novel findings on the association between intake of lutein, total folate, or isoflavones and risk of BE need further confirmation.     

Risk factors for Barrett’s esophagus: a scoping review

Introduction

Cancer of the esophagus is a highly lethal disease with many patients presenting with metastatic spread of their tumor at diagnosis; a consequence of this late presentation is the 5-year survival rate of <20 %. Barrett’s esophagus (BE), a premalignant condition of the distal esophagus, is the main risk factor for adenocarcinoma of the esophagus. The development of a risk prediction tool that could assist healthcare professionals in identifying people at increased risk of developing BE would be advantageous. Understanding the factors that influence the risk of developing BE is the first stage of developing a risk prediction tool.

Methods

A scoping review was undertaken to address the following question ‘what factors influence the risk of developing Barrett’s esophagus?’ Forty-six articles were included in this review.

Results

The majority of articles reviewed were case–control or cohort studies. Samples sizes ranged from 68 to 84,606. Risk factors reported to be statistically significant were divided into three categories: demographic, lifestyle and clinical factors. Strongest risk factors identified include: male gender, increasing age, white race, smoking, obesity and gastro-esophageal reflux disease symptoms, while some aspects of a person’s diet appear to act as a protective measure.

Conclusion

Risk factors for BE are complex and need to be considered by healthcare professionals when identifying patients that could benefit from endoscopic eradication. These results provide a stepping stone for the future development of a risk prediction model.

     

Prevalence of adenocarcinoma at esophagectomy for Barrett’s esophagus with high grade dysplasia

Background

Barrett’s esophagus with high grade dysplasia (HGD) may require surgical resection because of the risk of concomitant adenocarcinoma. The prevalence of invasive, occult carcinoma (≥stage 1B) in this setting has varied. We investigated the association of adenocarcinoma at operative resection for high grade dysplasia.

Methods

Using an electronic medical record, we identified patients who underwent esophagectomy for high grade dysplasia at the University of Pittsburgh Medical Center between 1993 and 2007. Preoperative diagnosis was confirmed by reviewing endoscopic, radiologic and pathology reports. Postoperative pathology reports were compared to the preoperative diagnosis.

Results

68 patients (12 females and 56 males) with a preoperative diagnosis of high grade dysplasia underwent operative resection. The mean age was 64 years (range 36 to 86 years). Of 68 patients, 12 (17.6%) had adenocarcinoma, 2 (2.9%) were downgraded to low grade dysplasia, and 54 (79.4%) were confirmed as HGD. Of the 12 patients with adenocarcinoma, 4 (5.9% of total cohort) had intramucosal cancer (Stage 1A) and 8 (11.7% of total cohort) had invasive cancer with submucosal invasion or more advanced disease. Of the 8 patients with invasive adenocarcinoma, 4 did not have preoperative endoscopic or radiologic testing suggestive of advanced disease.

Conclusion

The overall prevalence of adenocarcinoma in association with a preoperative diagnosis of HGD was 17.6%. Invasive adenocarcinoma was present in 11.7% of subjects and was clinically occult in 5.9%.     

Barrett’s esophagus in the patients with familial adenomatous polyposis

Familial adenomatous polyposis (FAP) is caused by germ line mutations in the APC gene. Barrett’s esophagus (BE) and Barrett’s adenocarcinoma are intestinal type lesions of the esophagus characterized by an early loss of heterozygosity at the APC locus. We hypothesized that patients with FAP are at risk for the early development of BE due to the inherited mutations in the APC gene (haploinsufficiency). Upper gastrointestinal (UGI) tract biopsies from 36 patients with FAP were reviewed to determine the incidence and characteristics of BE in these patients. Twenty-four patients were confirmed carriers of a deleterious germline APC mutation. The other 12 patients were from FAP families with known APC gene mutations and had clinical manifestations of FAP. The control group consisted of patients who did not have a personal or family history of FAP undergoing UGI endoscopic examination in our institution over a 30 month period of time. The difference in expression of Wnt pathway proteins (APC, β-catenin, E-cadherin and cyclin D1) in BE between BE⁺/FAP⁺, BE^?/FAP⁺ and age-matched BE⁺/FAP^? groups was studied using immunohistochemistry. BE was found in 6 of 36 (6/36 or 16%) patients with FAP and in 266 of 1662 patients (16%) in the control group of symptomatic patients. The average age at the first diagnosis of BE in FAP patients was 37.8 versus 57.5 years in the control group (sporadic BE). When compared to age matched BE⁺/FAP- group (7/334), patients with FAP had a significantly (p = 0.005843, odds ratio 9.2; Fisher exact test) higher incidence of BE. Both classic FAP and attenuated FAP phenotypes were associated with BE .Two types of germ line mutations in APC gene were identified in BE⁺/FAP⁺ patients: Five patients had 2-base deletion in exon 4 (426delAT) and one patient had 4-base deletion in exon 15 (3202del4). No difference in Wnt signaling pathway proteins expression was detected between BE⁺/FAP⁺ and the age matched group of patients with sporadic BE (BE⁺/FAP^?). Patients with FAP appear to have increased risk for the development of BE, which on average develops some 20 years earlier than in patients without FAP. This association needs to be taken in account when caring for the patients with FAP.     

Glycemic index, carbohydrate and fiber intakes and risk of reflux esophagitis, Barrett’s esophagus, and esophageal adenocarcinoma

Objective  To examine the association between dietary glycemic index (GI), glycemic load (GL), total carbohydrate, sugars, starch, and fiber intakes and the risk of reflux esophagitis, Barrett’s esophagus, and esophageal adenocarcinoma. Methods  In an all-Ireland study, dietary information was collected from patients with esophageal adenocarcinoma (n = 224), long-segment Barrett’s esophagus (n = 220), reflux esophagitis (n = 219), and population-based controls (n = 256). Multiple logistic regression analysis examined the association between dietary variables and disease risk by tertiles of intake and as continuous variables, while adjusting for potential confounders. Results  Reflux esophagitis risk was positively associated with starch intake and negatively associated with sugar intake. Barrett’s esophagus risk was significantly reduced in people in the highest versus the lowest tertile of fiber intake (OR 0.44 95%CI 0.25–0.80). Fiber intake was also associated with a reduced risk of esophageal adenocarcinoma, as was total carbohydrate intake (OR 0.45 95%CI 0.33–0.61 per 50 g/d increase). However, an increased esophageal adenocarcinoma risk was detected per 10 unit increase in GI intake (OR 1.42 95%CI 1.07–1.89). Conclusions  Our findings suggest that fiber intake is inversely associated with Barrett’s esophagus and esophageal adenocarcinoma risk. Esophageal adenocarcinoma risk is inversely associated with total carbohydrate consumption but positively associated with high GI intakes.     

Clinicopathological features of Siewert type II adenocarcinoma: comparison of gastric cardia adenocarcinoma and Barrett’s esophageal adenocarcinoma following endoscopic submucosal dissection

Objectives

Siewert type II esophagogastric junction adenocarcinoma encompasses both gastric cardia adenocarcinoma (GCA) and Barrett’s esophageal adenocarcinoma (BEA) due to short-segment Barrett’s esophagus. We compared these two types of Siewert type II esophagogastric junction adenocarcinoma in terms of background factors and clinical outcomes of endoscopic submucosal dissection (ESD).

Methods

We enrolled 139 patients (142 lesions) who underwent ESD from 2006 to 2014 at our institution. Background factors evaluated were age, sex, body mass index, hypertension, hyperlipidemia, hyperuricemia, diabetes mellitus, smoking, drinking, double cancer, and endoscopic findings. Clinical outcomes evaluated were procedure time, en bloc resection rate, curative resection rate, and adverse events.

Results

There were 87 GCA lesions (61.2%) and 55 BEA lesions. Features of BEA [55 lesions (38.8%)] included a younger age, small diameter, and a protruding type, along with a high frequency of esophageal hiatal hernia and less mucosal atrophy. There were no significant differences in lifestyle-related background factors between the GCA and BEA groups. Curative resection rate was greater for GCA (81%) than for BEA (66%) (P = 0.01). There were no serious adverse events in either group. Among the factors for noncurative resection, lymphovascular invasion and depth of invasion were greater for BEA (33.3 vs. 7 and 20.7 vs. 8.2%, respectively (P < 0.01). Of the noncured patients, 70% underwent additional surgery and none had postoperative lymph node metastasis.

Conclusions

Siewert type II adenocarcinoma encompasses two types of cancers with different etiologies: GCA and BEA. Although there are no significant differences in lifestyle-related background factors between GCA and BEA, BEA is a risk factor for noncurative resection via ESD.

     

Carney’s Triad: Case Report and Review

Introduction

Carney’s triad is a rare pathogenic entity which consists of the association in young women of multiple condromatosis in the lung, gastric leiomyosarcoma, and extradrenal paraganglioma; although the presence of three at the same time is not required for its diagnosis.

Case Report

We present the case of a 27-year-old woman who was diagnosed of pulmonary multiple hamartomatosis and gastric stromal tumor.

Discussion

A review of the literature shows the most important prognosis factors and therapeutic options. Surgery for gastrointestinal stromal tumors and extradrenal paraganglioma seems to be the best treatment up to date.     

Magnetic hyperthermia therapy for the treatment of glioblastoma: a review of the therapy’s history,efficacy and application in humans

Hyperthermia therapy (HT) is the exposure of a region of the body to elevated temperatures to achieve a therapeutic effect. HT anticancer properties and its potential as a cancer treatment have been studied for decades. Techniques used to achieve a localised hyperthermic effect include radiofrequency, ultrasound, microwave, laser and magnetic nanoparticles (MNPs). The use of MNPs for therapeutic hyperthermia generation is known as magnetic hyperthermia therapy (MHT) and was first attempted as a cancer therapy in 1957. However, despite more recent advancements, MHT has still not become part of the standard of care for cancer treatment. Certain challenges, such as accurate thermometry within the tumour mass and precise tumour heating, preclude its widespread application as a treatment modality for cancer. MHT is especially attractive for the treatment of glioblastoma (GBM), the most common and aggressive primary brain cancer in adults, which has no cure. In this review, the application of MHT as a therapeutic modality for GBM will be discussed. Its therapeutic efficacy, technical details, and major experimental and clinical findings will be reviewed and analysed. Finally, current limitations, areas of improvement, and future directions will be discussed in depth.     

HER2 status in Barrett’s esophagus & esophageal cancer: a meta analysis

Background

The oncogenic potential of the Human Epidermal Growth Factor Receptor 2 (HER2) is well known in the context of breast cancer however; its relationship with the development of Barrett’s Esophagus (BE) and Esophageal Cancer (EC) is unclear. The aim of this meta-analysis was to determine the overall prevalence and survival of HER2+ in BE & EC.

Patients and methods

Several databases were searched including article reference lists. Inclusion criteria required that studies measured HER2 positivity in subjects with BE or EC.

Results

33 studies were included in the meta-analysis (10 BE & 23 EC studies). The prevalence of HER2+ was found to be 24% (95% CI: 15-36%) in BE and 26% (95% CI: 19-34%) in EC. Squamous cell carcinoma (SCC) had a higher ER of 32% (95% CI: 20-48%) in comparison with adenocarcinoma (ADC) with an ER of 21% (95% CI: 14-32%). Sub group analyses showed a high geographical variance, Asia was found to be the highest prevalent area with an ER 42% (95% CI: 22-64%). The difference in survival rate between groups HER2- & HER2+ was found to be 7 months.

Conclusions

Our results highlight a high prevalence of HER2+ in subjects with adenocarcinoma. HER2+ appears to decrease the survival time of EC patients.     

Surveillance of Barrett’s oesophagus: Is it worthwhile?

ObjectiveTo assess the cost-effectiveness of surveillance of Barrett’s oesophagus.DesignCost-utility model.SettingUK NHS.PatientsOne thousand 55-year-old men with Barrett’s oesophagus.InterventionSurveillance programme: endoscopy and biopsy at 3 yearly intervals for non-dysplastic Barrett’s oesophagus; low-grade dysplasia yearly; high grade-dysplasia 3 monthly.Outcome measuresIncremental cost-effectiveness ratio, expected value of perfect information.ResultsNon-surveillance dominated surveillance (i.e. cost less and conferred more benefit), but there was substantial uncertainty around many of the model inputs. Probabilistic analyses showed that non-surveillance cost less and conferred more benefit in 75% of model runs. Surveillance was cost-effective at usual levels of willingness to pay in 11% of runs. For people with Barrett’s oesophagus in England and Wales, a value of £6.5 million is placed on acquiring perfect information about surveillance of Barrett’s oesophagus.ConclusionsThe PenTAG cost-utility model suggests that surveillance programmes do more harm than good.