Clinical and pathological outcomes in patients undergoing chemotherapy and resection for oesophageal and gastric adenocarcinoma in a newly established oesophago-gastric cancer centre

Abstract

Background: The incidence of oesophageal carcinoma (OCa) is increasing globally. In the world, it is the 8th most commonly diagnosed cancer, and 6th most common cause of cancer death. In Australia, oesophageal cancer is the 12th most commonly diagnosed cancer in males, and the 8th most common cause of cancer death. Historically, oesophageal and gastric adenocarcinomas (GCa) were two separate entities based on their anatomical location and histological features. However, the Western world has seen a rise in distal oesophageal adenocarcinoma, adenocarcinoma of the oesophagogatsric junction (OGJ), and intestinal-type gastric adenocarcinoma of the cardia. Subsequently much uncertainty now surrounds the characterization and management of these tumours, in particular, whether there is a link between oesophageal adenocarcinoma, and that of intestinal-type gastric adenocarcinoma. Furthermore OGJ adenocarcinomas are less well understood and it is unclear whether they fall into the spectrum of a similar condition, or are indeed an entity of their own. Multi-modality treatment has evolved to become standard of care, with surgery remaining a key component. The optimal surgical approach to oesophagectomy remains controversial. Minimally invasive oesophagectomy (MIO) has the theorectical benefit of reducing surgical trauma without compromising oncological outcome compared to traditional open surgery. Aims: The aims of this dissertation are two fold: 1. To review the current standard of care for the treatment of oesophageal cancer, with a focus on the trend towards multi-modality treatment, and operative strategies. I review our local protocols and present an audit of a single high-volume surgical unit. 2. Secondly to undertake SELDI-TOF analysis on tumour samples, comparing the protein profiles of OGJ tumours with oesophageal and gastric adenocarcinomas. Methods: 1. A retrospective review of a prospectively collected database was performed to audit the results of a single institution presented in Chapter 2. A prospectively maintained database was established in 2001. Data fields were based on those of the Association of Upper GI Surgeons of the UK and Ireland (AUGIS). Clinical, operative and pathological data for patients undergoing OG resection at our institution were recorded prospectively using datafields modelled on the AUGIS (Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland) database. Key parameters of care standards were examined including peri-operative mortality and morbidity, unscheduled return to operating theatre, anastomotic failure, lymph node count and circumferential margin positivity. These were compared to “acceptable” rates in the literature. 2. Ethical approval for this study was obtained from Northern Sydney Local Health District Human Research Ethics Committee (Reference number 1310-342M) in conjunction with approved protocol for access of tumour tissue from tumour bank. All patients with adenocarcinoma of the oesophagus and stomach were prospectively recorded in an electronic database and tumour bank was notified of each surgical procedure. Patient consent was obtained prior to surgical procedures. Each sample’s clinical details and histopathological report were reviewed and collated in a de-identified database. Any discrepancies were then discussed with the clinican/surgeon and a pathologist. A total of 53 samples were selected, 15 samples that were truly oesophageal adenocarcinoma without involvement of the OGJ, 17 samples were OGJ tumours with histological involvement of the OGJ and evidence of intestinal metaplasia, and 21 gastric adenocarcinomas which were at least 5cm away from the OGJ without involvement of the OGJ or the oesophagus. Specimens were prepared according to protocol and assessed using the SELDI-TOF MS method. Differential protein profiles were compared between the three groups of adenocarcinomas. Results: 1. Between December 2002 and May 2012, 134 patients were identified from our database as undergoing resection for oesophageal cancer by two surgeons or trainees under supervision in our specialised unit. Ninety-day mortality rate was 2.2%, with other key surgical performance indicators all falling within international acceptable standards. When comparing the two surgical approaches, post-operative mortality rates were 2.8% and 1.7% respectively for Open and MIO with no statistically significant difference in surgical and medical complications between the two procedures. We have not been able to demonstrate a benefit of one technique over the other. In terms of oncological outcomes, margin positivity and lymph node yield were not different between MIO and open oesophagectomy. The one significant finding we demonstrated was the higher stricture rate from MIO requiring dilatation. Our rate of 33% is consistent with other reported series of cervical anastomoses. Overall median survival for all patients was 42.6 months. When comparing the two operative techniques, there is no difference in overall or disease-specific survival. 2. The protein profiles of OCa, OGJ Ca and intestinal-type GCa have 34 peaks in common. Proteins with m/z8773 and 3046 can be used to differentiate between oesophageal and gastric adenocarcinoma. Using m/z8773 alone, it was able to predict oesophageal samples from gastric samples with accuracy of 82.8%, with the addition of m/z3046, the accuracy of differentiating the two tumours reached 100%. Applying this panel of two proteins to OGJ Ca, the junctional tumours demonstrated a pattern more closely resembling GCa, with the exception of one outlying specimen. Conclusion: Oesophagectomy can be performed at our institution with acceptable operative mortality and morbidity rates, furthermore, there were no differences in disease-specific or overall survival between the two surgical techniques. We have shown that oesophageal, OGJ and gastric cancers have differential protein profiles. Ongoing further studies with validation may prove beneficial in characterising OGJ cancers, and allow for improved staging, and potentially management strategies.