Renato A. Luna

Barrett’s Esophagus: A Review of the Literature

Barrett’s esophagus (BE) is the premalignant lesion of esophageal adenocarcinoma (EAC) defined as specialized intestinal metaplasia of the tubular esophagus that results from chronic gastroesophageal reflux. Which patients are at risk of having BE and which are at further risk of developing EAC has yet to be fully established. Many aspects of the management of BE have changed considerably in the past 5 years alone. The aim of this review is to define the critical elements necessary to effectively manage individuals with BE. The general prevalence of BE is estimated at 1.6–3% and follows a demographic distribution similar to EAC. Both short-segment (<3 cm) and long-segment (≥3 cm) BE confer a significant risk for EAC that is increased by the development of dysplasia. The treatment for flat high-grade dysplasia is endoscopic radiofrequency ablation therapy. The benefits of ablation for non-dysplastic BE and BE with low-grade dysplasia have yet to be validated. By understanding the intricacies of the development, screening, surveillance, and treatment of BE, new insights will be gained into the prevention and early detection of EAC that may ultimately lead to a reduction in morbidity and mortality in this patient population.

High-grade dysplasia and intramucosal adenocarcinoma in Barrett's esophagus: the role of esophagectomy in the era of endoscopic eradication therapy.

Purpose of review The aim of this review is to evaluate the role of esophagectomy for high-grade dysplasia (HGD) and intramucosal adenocarcinoma (IMC) in light of recent advances in endoscopic therapy for Barretts esophagus. Recent findings Radiofrequency ablation (RFA) and endoscopic mucosal resection (EMR) are proven well tolerated and effective, at least in midterm follow-up. The application of these techniques has opened a new road for the local treatment of esophageal HGD and IMC. To safely employ these techniques, reliable and accurate staging of the esophageal neoplasm is essential. EMR has taken a central role, as it allows the pathologist to provide tumor-staging information necessary for an appropriate clinical management decision process. Unfortunately, both RFA and EMR have limitations that preclude their universal use in the treatment of early esophageal cancer. In some cases, esophagectomy still remains the best treatment option. The evolution of the minimally invasive approach to esophagectomy may improve outcomes of this major operation. Summary A better understanding of the indications and limitations of endoscopic therapy for HGD and IMC permits a tailored approach to the management of patients with early esophageal adenocarcinoma. When indicated, the selection of a less morbid surgical technique has the potential to improve overall surgical and oncological outcomes.

Significant understaging is seen in clinically staged T2N0 esophageal cancer patients undergoing esophagectomy

This study aimed to determine the impact of preoperative staging on the treatment of clinical T2N0 (cT2N0) esophageal cancer patients undergoing esophagectomy. We reviewed a retrospective cohort of 27 patients treated at a single institution between 1999 and 2011. Clinical staging was performed with computed tomography, positron emission tomography, and endoscopic ultrasound. Patients were separated into two groups: neoadjuvant therapy followed by surgery (NEOSURG) and surgery alone (SURG). There were 11 patients (41%) in the NEOSURG group and 16 patients (59%) in the SURG group. In the NEOSURG group, three of 11 patients (27%) had a pathological complete response and eight (73%) were partial or nonresponders after neoadjuvant therapy. In the SURG group, nine of 16 patients (56%) were understaged, 6 (38%) were overstaged, and 1 (6%) was correctly staged. In the entire cohort, despite being clinically node negative, 14 of 27 patients (52%) had node-positive disease (5/11 [45%] in the NEOSURG group, and 9/16 [56%] in the SURG group). Overall survival rate was not statistically significant between the two groups (P = 0.96). Many cT2N0 patients are clinically understaged and show no preoperative evidence of node-positive disease. Consequently, neoadjuvant therapy may have a beneficial role in treatment.

Tailoring Esophageal Cancer Surgery

Esophageal cancer is a significant source of major mortality worldwide and is increasing dramatically in incidence. Without treatment this disease leads rapidly to death, but intervention also carries significant risk, so a carefully tailored approach must be used to maximize oncological efficacy while minimizing the negative consequences of intervention. Careful patient selection based on histologic and anatomic staging, consideration of each patients clinical variables, appropriately timing chemo- and radiation therapy, and minimizing the morbidity of surgical intervention may significantly improve a patients chances of surviving this disease, but each must be carefully orchestrated with a tailored approach to treatment. This review will serve as a guide to tailoring surgery for esophageal cancer.

Indications for Antireflux Surgery

Patients with frequent GERD symptoms cost the healthcare system billions of dollars annually—significantly more than non-GERD patients. Medical therapy (PPI) and antireflux surgery are the two accepted treatment options for these patients. Patients who respond to PPI therapy, at least partially, and have objective evidence of GERD demonstrated on upper endoscopy or pH study have better outcomes after surgery than those who do not. The objective of this chapter is to review the indications for surgical treatment in patients with GERD.

Is neoadjuvant therapy beneficial in clinically staged T2N0 esophageal cancer

135 Background: The optimal treatment strategy for clinical stage T2N0 (cT2N0) esophageal cancer is poorly defined. The specific aims of this analysis were to determine the impact of neoadjuvant therapy (NAT) in cT2N0 esophageal cancer patients on overall survival, nodal metastasis, staging, and pathological complete responders (pCR) NAT. Methods: We reviewed a retrospective cohort of 27 patients with cT2N0 esophageal cancer at Oregon Health & Science University, an NCI-Designated Cancer Center from 1999 to 2011. All patients were staged pre-operatively using Endoscopic Ultrasound (EUS), CT +/- FDG-PET. Patients were identified into two cohorts: NAT followed by surgery and surgery alone. We compared overall survival between the cohorts using Kaplan-Meier analysis. Results: Eleven patients (41%) received NAT followed by surgery and sixteen patients (59%) underwent surgery alone. Minimal invasive esophagectomy and decreased length of stay (p < 0.05) were associated with the presence of neoadjuvant therapy. ...

Neutrophil to lymphocyte ratios and pathologic response to neoadjuvant therapy in esophageal cancer.

44 Background: Esophageal cancer (EC) is increasing in incidence dramatically, and is associated with suboptimal outcomes despite the widespread adoption of neoadjuvant multimodality therapy (NAT) as a de-facto standard-of-care for clinically resectable disease. Between one-quarter and one-third of patients (pts) are found to have no evidence of tumor (pCR) at the time of surgical resection, a prognostic indicator of superior survival benefit. However, we currently lack a method to prospectively identify pts who will respond to (NAT). Identifying complete responders could reduce the number of patients requiring esophagectomy. The specific aim of this study was to determine if the pre-operative neutrophil to lymphocyte ratio (NLR), which has been reported as a prognosticator of mortality, is prognostic of pCR to NAT. METHODS A prospectively collected database was queried for all pts that have undergone esophagectomy for EC, including both squamous cell carcinoma and adenocarcinoma. Records were evaluated for preoperative complete blood count (CBC) with differential from which a NLR was calculated as the absolute neutrophil count divided by the absolute lymphocyte count. A NLR greater than 5 was considered elevated. Pts were classified as pCR if they had no residual tumor on final pathology, partial responders (PR) if they demonstrated down staging after neoadjuvant therapy, or non-responders (NR) if they did not show any improvement in their stage on final pathology. RESULTS Of 114 pts who underwent both NAT and esophagectomy for EC, 41 had a pre-operative CBC with differential from which a NLR could be calculated. There were 19 NR, 14 PR and 8 CR. These groups were demographically similar. The average NLR was 5.92 for NR, 6.56 for PR, and 4.89 among CR, with no statistically significant difference between groups. Overall survival at 5 years was 33%. By multivariate analysis NLR>5 did not correlate with pathologic response (p=0.78), and NLR >5 did not correlate with survival (p=0.33). CONCLUSIONS Elevated neutrophil to lymphocyte ratios are not predictive of pathologic response to NAT in esophageal cancer.