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      Improved Tissue Processing in Esophageal Adenocarcinoma After Ivor Lewis Esophagectomy Allows Histological Analysis of All Surgically Removed Lymph Nodes with Significant Effects on Nodal UICC Stages

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          Abstract

          Background

          In esophageal carcinoma, the numbers of metastatic and total removed lymph nodes (LN) are well-established variables of long-term prognosis. The overall rate of retrieved LN depends on neoadjuvant treatment, the extent of surgical lymphadenectomy, and the modality of the pathological workup. The question in this study is whether technically extended histopathological preparation can increase the number of detected (metastatic) LN with an impact on nodal UICC staging.

          Patients and Methods

          A cohort of 77 patients with esophageal adenocarcinoma was treated with Ivor Lewis esophagectomy including standardized two-field lymphadenectomy. The specimens were grossed, and all manually detectable LN were retrieved. The remaining tissue was completely embedded by the advanced “acetone compression” retrieval technique. The primary outcome parameter was the total number of detected lymph nodes before and after acetone workup.

          Results

          A mean number of 23,1 LN was diagnosed after standard manual LN preparation. With complete embedding of the fatty tissue using acetone compression, the number increased to 40.5 lymph nodes ( p < 0.0001). The mean number of metastatic LN increased from 3.2 to 4.2 nodal metastases following acetone compression ( p < 0.0001). Additional LN metastases which caused a change in the primary (y)pN stage were found in ten patients (13.0%).

          Conclusions

          Advanced lymph node retrieval by acetone compression allows a reliable statement on the real number of removed LN. Results demonstrate an impact on the nodal UICC stage. A future multicenter study will examine the prognostic impact of improved lymph node retrieval on long-term oncologic outcome.

          Supplementary Information

          The online version of this article contains supplementary material available at 10.1245/s10434-020-09450-1.

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          Most cited references19

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          Preoperative chemoradiotherapy for esophageal or junctional cancer.

          The role of neoadjuvant chemoradiotherapy in the treatment of patients with esophageal or esophagogastric-junction cancer is not well established. We compared chemoradiotherapy followed by surgery with surgery alone in this patient population. We randomly assigned patients with resectable tumors to receive surgery alone or weekly administration of carboplatin (doses titrated to achieve an area under the curve of 2 mg per milliliter per minute) and paclitaxel (50 mg per square meter of body-surface area) for 5 weeks and concurrent radiotherapy (41.4 Gy in 23 fractions, 5 days per week), followed by surgery. From March 2004 through December 2008, we enrolled 368 patients, 366 of whom were included in the analysis: 275 (75%) had adenocarcinoma, 84 (23%) had squamous-cell carcinoma, and 7 (2%) had large-cell undifferentiated carcinoma. Of the 366 patients, 178 were randomly assigned to chemoradiotherapy followed by surgery, and 188 to surgery alone. The most common major hematologic toxic effects in the chemoradiotherapy-surgery group were leukopenia (6%) and neutropenia (2%); the most common major nonhematologic toxic effects were anorexia (5%) and fatigue (3%). Complete resection with no tumor within 1 mm of the resection margins (R0) was achieved in 92% of patients in the chemoradiotherapy-surgery group versus 69% in the surgery group (P<0.001). A pathological complete response was achieved in 47 of 161 patients (29%) who underwent resection after chemoradiotherapy. Postoperative complications were similar in the two treatment groups, and in-hospital mortality was 4% in both. Median overall survival was 49.4 months in the chemoradiotherapy-surgery group versus 24.0 months in the surgery group. Overall survival was significantly better in the chemoradiotherapy-surgery group (hazard ratio, 0.657; 95% confidence interval, 0.495 to 0.871; P=0.003). Preoperative chemoradiotherapy improved survival among patients with potentially curable esophageal or esophagogastric-junction cancer. The regimen was associated with acceptable adverse-event rates. (Funded by the Dutch Cancer Foundation [KWF Kankerbestrijding]; Netherlands Trial Register number, NTR487.).
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            Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial

            Docetaxel-based chemotherapy is effective in metastatic gastric and gastro-oesophageal junction adenocarcinoma. This study reports on the safety and efficacy of the docetaxel-based triplet FLOT (fluorouracil plus leucovorin, oxaliplatin and docetaxel) as a perioperative therapy for patients with locally advanced, resectable tumours.
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              Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial.

              Initial results of the ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study (CROSS) comparing neoadjuvant chemoradiotherapy plus surgery versus surgery alone in patients with squamous cell carcinoma and adenocarcinoma of the oesophagus or oesophagogastric junction showed a significant increase in 5-year overall survival in favour of the neoadjuvant chemoradiotherapy plus surgery group after a median of 45 months' follow-up. In this Article, we report the long-term results after a minimum follow-up of 5 years.
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                Author and article information

                Contributors
                quaas.a@googlemail.com , alexander.quaas@uk-koeln.de
                Journal
                Ann Surg Oncol
                Ann Surg Oncol
                Annals of Surgical Oncology
                Springer International Publishing (Cham )
                1068-9265
                1534-4681
                10 December 2020
                10 December 2020
                2021
                : 28
                : 7
                : 3975-3982
                Affiliations
                [1 ]GRID grid.411097.a, ISNI 0000 0000 8852 305X, Institute of Pathology, Gastrointestinal Cancer Group Cologne (GCGC), , University Hospital Cologne, ; Cologne, Germany
                [2 ]GRID grid.411097.a, ISNI 0000 0000 8852 305X, Department of General, Visceral, Cancer and Transplantation Surgery, , University Hospital Cologne, ; Cologne, Germany
                [3 ]GRID grid.411097.a, ISNI 0000 0000 8852 305X, Department of Internal Medicine I, , University Hospital Cologne, ; Cologne, Germany
                [4 ]Institute of Pathology, Nordhessen and Targos Molecular Pathology GmbH, Kassel, Germany
                Article
                9450
                10.1245/s10434-020-09450-1
                8184552
                33305335
                13596c4d-3967-444a-a1bf-c7ad0049f1ac
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 4 September 2020
                : 16 November 2020
                Funding
                Funded by: Universitätsklinikum Köln (8977)
                Categories
                Thoracic Oncology
                Custom metadata
                © Society of Surgical Oncology 2021

                Oncology & Radiotherapy
                lymph nodes,acetone compression,esophageal adenocarcinoma,esophagectomy,uicc stage

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