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Superior Prognostic Importance of Perineural Invasion vs. Lymph Node Involvement After Curative Resection of Duodenal Adenocarcinoma

  • 2011 SSAT Plenary Presentation
  • Published:
Journal of Gastrointestinal Surgery Aims and scope

Abstract

Background

Unlike other gastrointestinal tumors, lymph node involvement has not consistently been a negative prognostic factor for survival in patients with duodenal adenocarcinoma. Our aim is to examine prognostic factors in patients who underwent a curative resection of their duodenal adenocarcinoma.

Methods

A retrospective review of 169 patients diagnosed with primary duodenal lesions between 1982 and 2010 was performed, of whom 103 were treated with curative intent. Clinico-pathologic factors were evaluated.

Results

A potentially curative resection was performed in 103 patients with a median age of 67 years (range, 22–91). Perineural and lympho-vascular invasion were identified in 30 (29.1%) and 39 patients (37.9%), respectively. Median follow-up was 26.5 months. The 5-year overall survival was 62% vs. 25% for patients with or without nodal metastases (p < 0.001) and 56% vs. 19% for patients with or without perineural invasion (p < 0.001), respectively. Lymph node ratio, type of resection, and size of tumor failed to stratify prognosis. By multivariate analysis, perineural invasion was the most powerful independent predictor of survival (HR, 2.520; CI, 1.361–4.664).

Conclusions

Perineural invasion is a stronger predictor for recurrence and survival than tumor size, depth of infiltration, lymph node involvement, and type of resection in patients with duodenal adenocarcinoma.

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Author information

Authors and Affiliations

  1. Department of Surgery, Massachusetts General Hospital, Boston, MA, USA

    Stefano Cecchini, Camilo Correa-Gallego, Matteo Ligorio, Abdulmetin Dursun, Jennifer Wargo, Carlos Fernàndez-del Castillo, Andrew Louis Warshaw & Cristina Rosa Ferrone

  2. Department of Pathology, Massachusetts General Hospital, Boston, MA, USA

    Vikram Desphande

  3. Department of General Surgery, Massachusetts General Hospital, Harvard Medical School, 15 Parkman Street, WAC 470F, Boston, MA, 02114-3117, USA

    Cristina Rosa Ferrone

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  1. Stefano Cecchini
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Correspondence to Cristina Rosa Ferrone.

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Discussant

Dr. Jean Nicolas Vauthey (Houston, TX): I congratulate Dr. Ferrone and her collaborators for another excellent contribution analyzing the factors associated with outcome following resection of duodenal adenocarcinoma. In this study, the authors show that the only independent predictor of outcome is perineural invasion while lymph node status or lymph node ratio, type of resection, or size of tumor fails to stratify prognosis. This study is in contrast with previous studies on pancreatic or biliary malignancies, and it suggests biologic differences associated with duodenal adenocarcinoma are linked to outcome.

I have three questions for the authors:

1. The number of pathology blocks and the intensity of the review may affect the yield of a pathological study. How many blocks were reviewed per specimen? The authorship indicates that one pathologist reviewed the slides. What is the interobserver agreement of a pathological review of perineural invasion?

Rodriguez-Urrego PA, Cronin AM, Al-Ahmadie HA, Gopalan A, Tickoo SK, Reuter VE, Fine SW. Interobserver and intraobserver reproducibility in digital and routine microscopic assessment of prostate needle biopsies. Hum Pathol. 2011 Jan; 42(1):68–74. Epub 2010 Oct 20. PubMed PMID: 20970164.

2. The fact that lymph node status or tumor size failed to correlate with prognosis is somewhat unexpected. Do the authors feel that these findings are related to the biology of the tumor or the quality and extent of their surgical resection and lymph node dissection?

3. The authors have previously correlated the biology of ampullary carcinoma with telomerase and hTERT. Can the authors speculate and provide a basic science explanation for their interesting findings?

Liebig C, Ayala G, Wilks JA, Berger DH, Albo D. Perineural invasion in cancer: a review of the literature. Cancer. 2009 Aug 1; 115(15):3379–91. Review.

Closing Discussant

Dr. Cristina Ferrone: Thank you for your thoughtful questions.

We reviewed three blocks per specimen. Since all of the specimens were originally reviewed by a GI pathologist, we felt that re-review of the slides by a single senior GI pathologist was sufficient. According to a study performed in prostate cancer, the interobserver agreement for perineural invasion amongst four pathologists is good (k, 0.55).

Over the past decade, the prognostic value of tumor size and lymph node status in duodenal adenocarcinoma has been frequently debated. Neither factor consistently emerges as a significant prognostic factor in large retrospective series. In our series, LN status was significant on univariate analysis, but lost its significance on multivariate analysis because of the superior prognostic power of perineural invasion. It appears that the biology of the tumor, as yet incompletely known, once again is king.

Our search of the literature has turned up no correlation between telomerase and perineural invasion. We do know that perineural invasion is the result of a complex set of interactions between tumor cells, nerve cells, and stromal cells. These interactions are still incompletely understood. Perineural invasion has been most extensively studied in pancreatic, prostate, and colorectal cancers and is consistently associated with a decreased survival. Certain neurotrophic factors and metalloproteinases clearly play a role in perineural invasion. We assume that these factors may also contribute to perineural invasion in duodenal adenocarcinoma.

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Cecchini, S., Correa-Gallego, C., Desphande, V. et al. Superior Prognostic Importance of Perineural Invasion vs. Lymph Node Involvement After Curative Resection of Duodenal Adenocarcinoma. J Gastrointest Surg 16, 113–120 (2012). https://doi.org/10.1007/s11605-011-1704-6

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  • DOI: https://doi.org/10.1007/s11605-011-1704-6

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