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Can the Risk of Lymph Node Metastases Be Gauged in Endoscopically Resected Submucosal Esophageal Adenocarcinomas? A Multi-Center Study

  • 2015 SSAT Plenary Presentation
  • Published:
Journal of Gastrointestinal Surgery Aims and scope

Abstract

Endoscopic resection (ER) allows for local therapy of superficial esophageal cancers. Factors reported to be associated with an increased risk of lymph node metastases in patients with adenocarcinoma are poor differentiation, lymphovascular invasion (LVI), and submucosal invasion >500 μ. The aim of this study was to determine whether depth of invasion and tumor characteristics in an ER specimen can be used to gauge the risk of lymph node metastases in patients with superficial esophageal adenocarcinoma. Patients from seven US centers that had ER of an adenocarcinoma followed by an esophagectomy were identified. The ER pathology slides were rereviewed by three experienced GI pathologists for depth of invasion, presence of LVI, and tumor differentiation. The findings from the ER specimen were correlated with the presence and number of lymph node metastases in the final esophagectomy specimen. There were 19 T1a and 23 T1b tumors. A median of 24 nodes were resected per patient. None of the T1a tumors had involved lymph nodes despite the presence of LVI in 5 % and poor differentiation in 21 % of patients. In contrast, 26 % of T1b tumors had involved nodes. None of the four patients with submucosal invasion ≤500 μ, no LVI, and no poor differentiation had involved nodes. However, with an increasing number of risk factors, the likelihood of involved lymph nodes increased, reaching 50 % when all three factors were present. Endoscopic therapy appears appropriate for intramucosal tumors and may be an option for low-risk T1b tumors. Esophagectomy is preferred for patients with submucosal invasion and one or more risk factors.

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Acknowledgments

This study was made possible by the generous donation of a grateful patient with Barrett’s esophagus.

Author information

Authors and Affiliations

  1. Department of Surgery, Keck School of Medicine, University of Southern California, 1510 San Pablo St, Suite 514, Los Angeles, CA, 90033, USA

    Joshua A. Boys, Stephanie G. Worrell & Steven R. DeMeester

  2. Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    Parakrama Chandrasoma & John G. Vallone

  3. Department of Pathology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA

    Dipen M. Maru

  4. Department of Pathology, Mayo Clinic, Rochester, MN, USA

    Lizhi Zhang

  5. Department of Surgery, Mayo Clinic, Rochester, MN, USA

    Shanda H. Blackmon & Karen J. Dickinson

  6. Department of Surgery, Oregon Clinic, Portland, OR, USA

    Christy M. Dunst

  7. Department of Surgery, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA

    Wayne L. Hofstetter

  8. Department of Surgery, University of Rochester, New York, NY, USA

    Michael J. Lada & Thomas J. Watson

  9. Department of Surgery, Swedish Cancer Institute, Seattle, WA, USA

    Brian E. Louie

  10. Department of Surgery, Johns Hopkins University, Baltimore, MD, USA

    Daniela Molena

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  1. Joshua A. Boys
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Correspondence to Steven R. DeMeester.

Additional information

Primary Discussant

Sumeet K. Mittal, M.D. (Omaha, NE)

A very thoughtful and timely presentation. The question they have tried to answer is: “can the risk of lymph node metastasis be gauged in Endoscopically resected submucosal EAC ?”

Of 42 patients meeting inclusion criteria, the biggest risk factor for LN disease was submucosal extension. Other known risk factors namely Lymph vascular invasion, depth of submucosal invasion, and tumor differentiation increased the risk of LN. NO LN mets if none are present. They conclude that “low-risk submucal cancer” may be watch just with endoscopic therapy. Numbers are too small to make such conclusions.

The other important thing they point out in the article they send me though not in the slides is that 48 % of patients had their original EMR specimen diagnosis changed based on reevaluation by expert pathologist. This too when presumably experienced pathologist saw the original specimen at these highly respected institutions. This is additional variability in day-to-day situation with respect to specimen processing and local expertize. This is quite worrisome and brings into question of reliability in general practice.

I have three questions for the authors:

1. Were there any patients who had a diagnosis of mucosal cancer on EMR and were found to have submucosal extension on the resected specimen.

2. It is safe to conclude that at least a few patients (not part of this study) diagnosed with T1a cancer are in fact T1b and are being undertreated with endoscopic therapy alone. Do you have f/u data on T1a endoscopically treated cancers at your seven institutions and have there been any recurrences. How do you recommend follow-up for these patients only EGD or including EUS and at what intervals and for how long.

3. You have mentioned width of tumor at muscularis mucosa interface with depth of uninvolved submucosa being a potential marker for LN metastasis. Can you elaborate on that please?

Closing Discussant

Dr. DeMeester

1. Yes, there were six cases with an intramucosal tumor on ER but a submucosal tumor in the esophagectomy specimen. These patients were excluded from analysis. What is unclear is whether the submucosal tumor was a missed deep extension of the tumor treated by ER or, more likely, if this was a separate tumor in a patient with multifocal disease. Remember, ER for both staging and therapy was accepted at the participating centers, so an esophagectomy for a T1a lesion was prompted by some concern or suspicion. This issue was really not a focus of our study, but clearly, this happens in clinical practice, and it is imperative that treating physicians consider the potential for multifocal or more advanced disease in each individual patient when trying to decide whether or not to continue with endoscopic therapy or moving forward with resection. That is also one of the limitations of our study, and all these patients had an esophagectomy for some reason, either T1b tumor or concern about multifocal disease or incomplete resection of a T1a lesion.

2. In a companion study, also being presented here at DDW, we looked at the issue of variability in the pathologic assessment of ER specimens. Incredibly, we found an almost 50 % error rate overall. There are a lot of complexities to interpreting an ER specimen, and understaging or overstaging can lead to inappropriate endotherapy for a more advanced lesion, or to an esophagectomy in a patient where it was perhaps not necessary for limited T1a disease. However, in this study, all patients went on to esophagectomy after ER, so we are not able to address the issue of recurrence and outcome with endotherapy alone. I would refer you to the incredible series by Ell and colleagues of 1000 patients treated with endotherapy and really excellent outcomes. I don’t think that the safety and efficacy of endotherapy for a T1a lesion is really a question any longer. Instead, the focus of this study was on how far we can safely push endotherapy with deeper lesions and in the presence of risk factors for node metastases.

If we do treat a patient endoscopically, our routine is rebiopsy in 8 weeks and retreatment for residual intestinal metaplasia or dysplasia. This cycle is repeated until all intestinal metaplasia is gone, then patients enter endoscopic surveillance every 3 months for 1 year, every 6 months for the next year, and then annually. We do not use routine EUS in follow-up.

3. We were intrigued since while looking at these ER specimens, we observed that the tumor width at the mucosal/submucosal junction was often greater than the depth of invasion into the submucosa, and we wondered if this would be important with regard to the risk of node metastases. We also wondered if the free submucosal margin below the tumor would have some relevance. We did not find that either of these measurements correlated with node disease in this relatively small series. Nonetheless, it is possible that submucosal tumor volume may play a role in the risk of node disease, similar to gross tumor size, so we will continue to explore these concepts in future studies.

Thank you Dr. Mittal for these important questions and comments.

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Boys, J.A., Worrell, S.G., Chandrasoma, P. et al. Can the Risk of Lymph Node Metastases Be Gauged in Endoscopically Resected Submucosal Esophageal Adenocarcinomas? A Multi-Center Study. J Gastrointest Surg 20, 6–12 (2016). https://doi.org/10.1007/s11605-015-2950-9

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