Combination treatments.

It has been shown that postoperative radiation and chemotherapy do not increase survival in adenocarcinoma. Preoperative chemotherapy alone is not helpful, although there is a recent paper in the New England Journal of a large multi-center study confirming that again. Presently, preoperative, so-called neoadjuvant, chemotherapy plus radiotherapy looks somewhat more promising,. with radiation being given to improve control over local disease, and sometimes by the time the operation is done, about 20 to 25% of patients do not have any tumor left, and with chemotherapy to control micrometastases, which are present in so many of these patients, but of course can’t be seen but show up as distant metastases at a later date. Thinking was changed by this paper from Walsh and his colleagues in Dublin, Ireland, which appeared in the New England Journal in 1966. They took about 113 patients and randomized them to either have surgery alone or to have surgery preceded by multimodal therapy, which was 5-FU plus cisplatin plus radiation to the primary tumor. As you will see, by three years the survival was much better in the patients given the neoadjuvant preoperative therapy compared to proceeding immediately to surgery.

While it is fairly difficult to do radiation and chemotherapy, it has its own problems and complications and this paper, it was decided at our institution, was not enough to change the entire thinking and to proceed on this one paper alone. There was a smaller one from the University of Michigan with a similar trend to give everyone preoperative therapy. So the present situation is that we surgeons, oncologists and radiation therapists are collaborating with multiple other North American centers in the CALGB-97 study, which is attempting to reproduce this study with preop chemo and radiation followed by surgery versus surgery alone. We are randomizing patients into that study, but it will be several years before the results are finally determined.

I’m afraid that for many patients, possibly half of all patients with adenocarcinoma of the esophagus presenting with symptoms, an operation is not possible because of distant metastases, because of age or other medical conditions, and sometimes all that can be done is the endoscopic placement of a metal spring stent to enable them to be swallow, as is being done here.

Let’s go back to Barrett’s esophagus, the place where most adenocarcinomas of the esophagus begin. Normally, all of your esophagus is lined with pale pink squamous mucosa and the Z line, the junction, should be at the lower end of the esophagus. In Barrett’s esophagus, a variable length of lower esophagus is lined with red columnar epithelium, easily seen at endoscopy. Barrett’s esophagus is an acquired condition and is associated with severe gastroesophageal reflux. Most patients will have a weak lower esophageal sphincter and over 90% of patients will also have a sliding hiatal hernia. These are at least two of the factors that probably cause reflux to occur, reflux then damaging the normal squamous lining here, which becomes replaced later by columnar. This is an acquired condition and this is an interesting and unusual patient, but we are showing a typical finding, a patient with reflux symptoms. On the left here, biopsy from the lower esophagus shows squamous epithelium with changes of esophagitis, elongated papillae and a thickened basal cell here.

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