Daniel Tong

Barrett's esophagus: cancer and molecular biology

The following paper on the molecular biology of Barretts esophagus (BE) includes commentaries on signaling pathways central to the development of BE including Hh, NF‐κB, and IL‐6/STAT3; surgical approaches for esophagectomy and classification of lesions by appropriate therapy; the debate over the merits of minimally invasive esophagectomy versus open surgery; outcomes for patients with pharyngolaryngoesophagectomy; the applications of neoadjuvant chemotherapy and chemoradiotherapy; animal models examining the surgical models of BE and esophageal adenocarcinoma; the roles of various morphogens and Cdx2 in BE; and the use of in vitro BE models for chemoprevention studies.

Extended lymphadenectomy in esophageal cancer is crucial.

Surgery with lymphadenectomy remains the mainstay of treatment for esophageal cancer. The optimal extent of nodal dissection is controversial. Evidence is accumulating, however, that could demonstrate the benefits of extended lymphadenectomy, which include more accurate disease staging, better locoregional disease control, and improved survival. Except in very early disease where nodal metastases are rare, extended lymphadenectomy is indicated. Data from a randomized controlled trial comparing transhiatal and transthoracic resection have shown better survival in patients with limited nodal burden. Other investigations on en bloc resection, three-field lymphadenectomy, and large-scale international collaborative studies have all provided evidence for the more extensive approach to enhance cure for esophageal cancer. The more extended surgery does lead to potentially higher morbidity rates, and thus surgeons should be versatile in applying such techniques in carefully selected patients, so that postoperative survival and quality of life of patients are not compromised. The challenge in the future is how to tailor surgical strategies for individual patients in order to achieve the best outcome.

Hong Kong Experience

Esophageal cancer is the sixth most common cancer in the world [1]. There has been a divergence of histological cell type between the East and West. In western countries, adenocarcinoma has increased dramatically in incidence in the past 30 years, closely related to rising prevalence of obesity, gastroesophageal reflux disease, and Barrett’s esophagus. In Asia, esophageal squamous cell carcinoma (ESCC) remains the predominant cell type; more than 80 % of esophageal cancer is squamous cell in origin. There has not been a convincing rise in incidence of true adenocarcinoma of the esophagus (Siewert type I) in Asia. In Hong Kong, ESCC accounts for more than 90 % of all esophageal cancers. In 2010, the Cancer Registry of Hong Kong identified esophageal cancer as the eighth leading cause of cancer deaths. The overall 5-year survival rate was disappointing at around 20 % only [2].

Esophageal Squamous Cell Cancer: Pathogenesis and Epidemiology

Esophageal cancer is a highly lethal disease. Despite the rapidly increasing incidence of adenocarcinoma in last decades, squamous cell carcinoma remains the predominant cell type worldwide. The majority of squamous cell cancers are from Eastern populations. Risk factors for the development of esophageal squamous cell carcinoma differ between high and low incidence regions. Tobacco and alcohol intake are the two major risks factors for esophageal squamous cell carcinoma. They also have a synergistic effect; the mechanism of which is now better understood. Other dietary factors include lack of certain micronutrients such as vitamins and minerals, consumption of food with carcinogenic ingredients, eating habits and food preservation methods. Genetic factors, viral infection and other premalignant conditions also play a role. Studying epidemiology and pathogenesis of the disease allows policymakers to enact public health policies to prevent the disease through health education and risk factors avoidance. Screening for early disease detection in high-risk populations could improve overall outcome.

Outcomes after oesophageal perforation: a retrospective cohort study of patients with different aetiologies

INTRODUCTION The mortality rate after oesophageal perforation is high despite advances in operative and non-operative techniques. In this study, we sought to identify risk factors for hospital mortality after oesophageal perforation treatment. METHODS We retrospectively examined patients treated for oesophageal perforation in a university teaching hospital in Hong Kong between January 1997 and December 2013. Their demographic and clinical characteristics, aetiology, management strategies, and outcomes were recorded and analysed. RESULTS We identified a cohort of 43 patients treated for perforation of the oesophagus (28 men; median age, 66 years; age range, 30-98 years). Perforation was spontaneous in 22 (51.2%) patients (15 with Boerhaaves syndrome and seven with malignant perforation), iatrogenic in 15 (34.9%), and provoked by foreign body ingestion in six (14.0%). Of the patients, 14 (32.6%) had pre-existing oesophageal disease. Perforation occurred in the intrathoracic oesophagus in 30 (69.8%) patients. Emergent surgery was undertaken in 23 patients: 16 underwent primary repair, six surgical drainage or exclusion, and one oesophagectomy. Twenty patients were managed non-operatively, 13 of whom underwent stenting. Two stented patients subsequently required oesophagectomy. Four patients had clinical signs of leak after primary repair: two were treated conservatively and two required oesophagectomy. Overall, six (14.0%) patients required oesophagectomy, one of whom died. Nine other patients also died in hospital; the hospital mortality rate was 23.3%. Pre-existing pulmonary and hepatic disease, and perforation associated with malignancy were significantly associated with hospital mortality (P=0.03, <0.01, and <0.01, respectively). CONCLUSIONS Most oesophageal perforations were spontaneous. Mortality was substantial despite modern therapies. Presence of pre-existing pulmonary disease, hepatic disease, and perforation associated with malignancy were significantly associated with hospital mortality. Salvage oesophagectomy was successful in selected patients.

Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphoma: magnifying endoscopy findings.

Gastric mucosa-associated lymphoid tissue lymphoma is uncommon and most patients have an indolent clinical course. The clinical presentation and endoscopic findings can be subtle and diagnosis can be missed on white light endoscopy. Magnifying endoscopy may help identify the abnormal microstructural and microvascular patterns, and target biopsies can be performed. We describe herein the case of a 64-year-old woman with Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphoma diagnosed by screening magnification endoscopy. Helicobacter pylori-eradication therapy was given and she received biological therapy. She is in clinical remission after treatment. The use of magnification endoscopy in gastric mucosa-associated lymphoid tissue lymphoma and its management are reviewed.

Tu1540 Prognostic Factors After Esophagectomy for Squamous Cell Carcinoma of the Esophagus - Does Tumor Location Matter?

INTRODUCTION: As pre-operative chemoradiation followed by esophagectomy has become standard therapy in patients with resectable esophageal adenocarcinoma (EAC), traditional pathological staging has become a less useful prognostic tool. The 7th edition of the American Joint Commission on Cancer (AJCC7) staging system for EAC is derived from data on patients undergoing esophagectomy without neoadjuvant therapy and classifies lymph node status by the number of involved lymph nodes. Lymph node harvest (LNH) and lymph node positivity ratio (LNPR) have been suggested to be prognostic indicators but have not found widespread support. In an effort to develop a valid staging model in the era of neoadjuvant therapy, we compared the predictive value of LNH and LNPR to AJCC7 staging in a large cohort of patients undergoing resection for EAC. METHODS: The study population consisted of 316 patients who underwent R0 esophagectomy for EAC from 1/00 to 12/11 (86% male; mean age 64.0±10.3 years). Survival functions were estimated using the KaplanMeier method. Classification thresholds for both LNPR and LNH were derived by recursive partitioning using conditional inference trees comparing survival functions. Based on these analyses, LNPR was stratified and Cox proportional hazards regression models were used to compare predictive value of lymph node categorization strata. RESULTS: Median lymph node harvest was 12 (IQR 7-20). 51% of patients were N0, 29% N1, 13% N2. Median overall survival was 63.4 months (95%CI 40.6 92.3) and 5-year overall survival was 50.7% (95%CI 45.0 57.2). Eighty-three patients (26%) received neoadjuvant chemotherapy, radiation therapy or both. In patients who received neoadjuvant therapy and had no lymph node metastasis identified (40/83; 48%), recursive partitioning analysis yielded a LNH threshold of 15 for discrimination of survival functions. LNH ≥ 15 was associated with a significant survival advantage (3-year survival 95 vs. 38%; p = 0.000022). Similarly, recursive partitioning analysis yielded LNPR categories of less than 20%, 20-40%, or greater than 40% as significantly discriminant of survival functions. In patients who received neoadjuvant therapy, LNPR was more predictive of survival than number of positive lymph nodes as categorized by AJCC7 (p=0.00018 vs. 0.033). In the 256 patients who received no neoadjuvant therapy, LNH was not a significant predictor of survival after node negative resection, although LNPR was a stronger predictor of survival than the current nodal staging system (p-value 0.000015 vs. 0.05). CONCLUSION: For patients receiving neoadjuvant therapy, both LNH and LNPR are more predictive of survival than the number of lymph node metastases detected in esophagectomy specimens. A minimum LNH of 15 is necessary to establish reliable N0 staging in this cohort.