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Chopko TC, Maroun JW, Reisenauer JS, Tapias LF. Sentinel Lymph Node Mapping in Esophageal Cancer: Current Status and Future Directions. Ann Surg Oncol 2025:10.1245/s10434-025-17479-3. [PMID: 40402425 DOI: 10.1245/s10434-025-17479-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2025] [Accepted: 04/28/2025] [Indexed: 05/23/2025]
Abstract
OBJECTIVE This review provides a comprehensive discussion about the importance of adequate lymphadenectomy, its anatomic and oncologic significance, principles and rationale of sentinel lymph node mapping, current evidence stratified by tracer substrate, challenges, and future directions. Esophageal cancer has one of the worst cancer-related survival rates, and nodal status is the single most significant prognostic factor. Submucosal penetration generally demands esophagectomy, often following neoadjuvant therapy in the presence of deeper extension. Guidelines recommend resecting ≥15 lymph nodes. Variability in surgical approach and dissection in concert with aberrant esophageal lymphatic anatomy make adequate lymphadenectomy difficult. METHODS A narrative review was conducted to explore existing literature regarding lymphadenectomy with its requisite anatomic and oncologic significance in esophageal cancer, as well as the rationale for and present state of sentinel lymph node mapping stratified by substrates. Tables and figures were constructed by the authors using Microsoft Office applications and Biorender software, respectively. RESULTS Sentinel lymph node mapping exploits the tumoral lymphatic network to identify the nodes most prone to metastasis, directing further dissection. Targeting sentinel lymph nodes with dyes, radiotracers, or hybrid tracers can assist surgeons with lymphadenectomy, potentially improving staging accuracy and personalizing care to individual anatomy. CONCLUSIONS While this approach would benefit from larger studies and long-term data, early evaluations suggest improved detection of metastases outside the en bloc field without significantly increasing morbidity.
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Affiliation(s)
| | | | - Janani S Reisenauer
- Division of Thoracic Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, USA
| | - Luis F Tapias
- Division of Thoracic Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, USA.
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Minimally invasive total adventitial resection of the cardia for tumours of the oesophagogastric junction. Langenbecks Arch Surg 2021; 406:2273-2285. [PMID: 33904977 DOI: 10.1007/s00423-021-02174-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Accepted: 04/11/2021] [Indexed: 02/07/2023]
Abstract
PURPOSE A cohort study analysing phases and outcomes of the learning curve required to master minimally invasive total adventitial resection of the cardia. METHODS Data from 198 consecutive oesophagectomies performed by a single surgeon was collected prospectively. Patients' stratification reflected chronologically and technically the four main phases of the learning curve: open surgery (open total adventitial resection of the cardia (TARC), n = 45), hybrid Ivor Lewis oesophagectomy (HILO, n = 50), laparoscopic-thoracoscopic assisted (LTA, n = 56) and totally minimally invasive TARC (TMI TARC, n = 47). Operating time, hospital stay, specimen lymph nodes and resection margins were analysed. Five-year survival was the main long-term outcome measured. RESULTS Overall 5-year survival was 45%. Perioperative mortality was 1.5% (n = 3). Hospital stay was 22 ± 23 days. Specimen lymph node median was 20 (range: 15-26). Resection margins were negative (R = 0, American College of Pathologists) in 193 cases (97.4%). Five-year survival in the four phases was 37.8%, 44.9%, 42.9% and 55.3%, showing a positive trend towards the end of the learning curve (p = 0.024). Median specimen lymph nodes was 20 (range: 15-22) for open TARC, 18.5 (13-25) for HILO, 19.5 (15-25) for LTA and 23 (18-30) for TMI TARC (p = 0.006). TMI TARC, adenocarcinoma, R >0, T >2, N >0 and LyRa (ratio positive/total specimen nodes) were associated with survival on univariate analysis. T >2 and LyRa independently predicted worse survival on multivariate analysis. CUSUM analysis showed surgical proficiency gain since laparoscopy was introduced. CONCLUSION Mastering minimally invasive TARC requires a long learning curve. TMI TARC is safe and oncologically appropriate and may benefit long-term survival: it should be validated by randomised trials as a standardised anatomical resection for tumours of the oesophagogastric junction.
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Mahieu R, de Maar JS, Nieuwenhuis ER, Deckers R, Moonen C, Alic L, ten Haken B, de Keizer B, de Bree R. New Developments in Imaging for Sentinel Lymph Node Biopsy in Early-Stage Oral Cavity Squamous Cell Carcinoma. Cancers (Basel) 2020; 12:cancers12103055. [PMID: 33092093 PMCID: PMC7589685 DOI: 10.3390/cancers12103055] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2020] [Revised: 10/03/2020] [Accepted: 10/15/2020] [Indexed: 12/18/2022] Open
Abstract
Sentinel lymph node biopsy (SLNB) is a diagnostic staging procedure that aims to identify the first draining lymph node(s) from the primary tumor, the sentinel lymph nodes (SLN), as their histopathological status reflects the histopathological status of the rest of the nodal basin. The routine SLNB procedure consists of peritumoral injections with a technetium-99m [99mTc]-labelled radiotracer followed by lymphoscintigraphy and SPECT-CT imaging. Based on these imaging results, the identified SLNs are marked for surgical extirpation and are subjected to histopathological assessment. The routine SLNB procedure has proven to reliably stage the clinically negative neck in early-stage oral squamous cell carcinoma (OSCC). However, an infamous limitation arises in situations where SLNs are located in close vicinity of the tracer injection site. In these cases, the hotspot of the injection site can hide adjacent SLNs and hamper the discrimination between tracer injection site and SLNs (shine-through phenomenon). Therefore, technical developments are needed to bring the diagnostic accuracy of SLNB for early-stage OSCC to a higher level. This review evaluates novel SLNB imaging techniques for early-stage OSCC: MR lymphography, CT lymphography, PET lymphoscintigraphy and contrast-enhanced lymphosonography. Furthermore, their reported diagnostic accuracy is described and their relative merits, disadvantages and potential applications are outlined.
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Affiliation(s)
- Rutger Mahieu
- Department of Head and Neck Surgical Oncology, University Medical Center Utrecht, University of Utrecht, 3584 CX Utrecht, The Netherlands;
| | - Josanne S. de Maar
- Division of Imaging and Oncology, University Medical Center Utrecht, University of Utrecht, 3584 CX Utrecht, The Netherlands; (J.S.d.M.); (R.D.); (C.M.)
| | - Eliane R. Nieuwenhuis
- Department of Magnetic Detection & Imaging, University of Twente, 7522 NB Enschede, The Netherlands; (E.R.N.); (L.A.); (B.t.H.)
| | - Roel Deckers
- Division of Imaging and Oncology, University Medical Center Utrecht, University of Utrecht, 3584 CX Utrecht, The Netherlands; (J.S.d.M.); (R.D.); (C.M.)
| | - Chrit Moonen
- Division of Imaging and Oncology, University Medical Center Utrecht, University of Utrecht, 3584 CX Utrecht, The Netherlands; (J.S.d.M.); (R.D.); (C.M.)
| | - Lejla Alic
- Department of Magnetic Detection & Imaging, University of Twente, 7522 NB Enschede, The Netherlands; (E.R.N.); (L.A.); (B.t.H.)
| | - Bennie ten Haken
- Department of Magnetic Detection & Imaging, University of Twente, 7522 NB Enschede, The Netherlands; (E.R.N.); (L.A.); (B.t.H.)
| | - Bart de Keizer
- Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands;
| | - Remco de Bree
- Department of Head and Neck Surgical Oncology, University Medical Center Utrecht, University of Utrecht, 3584 CX Utrecht, The Netherlands;
- Correspondence: ; Tel.: +31-88-7550819
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Wang A, Lu L, Fan J, Wang S, Chen X. Lymph node metastatic patterns and its clinical significance for thoracic superficial esophageal squamous cell carcinoma. J Cardiothorac Surg 2020; 15:262. [PMID: 32958015 PMCID: PMC7507729 DOI: 10.1186/s13019-020-01302-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Accepted: 09/08/2020] [Indexed: 01/02/2023] Open
Abstract
Background and objectives The optimal therapeutic method for patients with superficial esophageal squamous cell carcinoma (sESCC) remains to be established. Methods Clinical data of all the patients from 2002 to 2014 who underwent curative esophagectomy and three-field lymphadenectomy for thoracic sESCC were collected based on a prospectively-maintained database. The pattern of lymph node metastasis was analyzed based on the depth of tumor invasion, tumor location and surgical fields. Results The involved lymph node region was associated to the tumor location, however, upper mediastinal and perigastric region was the most vulnerable region. The incidence of lymph node metastasis increased with the depth of tumor invasion. No lymph node involvement was found in tumors invading proper mucosa (M2), while the pattern of positive lymph nodes in tumors invading the deepest 1/3 submucosa was similar to that in advanced ESCC. Lymphatic invasion, tumor location and upper mediastinal lymph node involvement were independent predictors for cervical lymph node metastasis. For patients without lymphatic invasion, the positive predictive value of upper mediastinal lymph node metastasis for positive cervical lymph node was low (0 ~ 25%), while the negative predictive value was extremely high, wherever the tumor located (93.8 ~ 100%). Conclusions Tumors invading till proper mucosa was the best indication for endoscopic mucosa resection. Mediastinal-abdominal lymphadenectomy was essential for sESCC invading beyond proper mucosa. For those without lymphatic invasion, cervical lymphadenectomy might be avoided in case of negative upper mediastinal lymph node.
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Affiliation(s)
- An Wang
- Department of Thoracic Surgery, Huashan Hospital, Fudan University, Shanghai, China
| | - Lu Lu
- Department of Pathology, Huashan Hospital, Fudan University, Shanghai, China
| | - Jie Fan
- Department of Pathology, Huashan Hospital, Fudan University, Shanghai, China
| | - Shaohua Wang
- Department of Thoracic Surgery, Huashan Hospital, Fudan University, Shanghai, China.
| | - Xiaofeng Chen
- Department of Thoracic Surgery, Huashan Hospital, Fudan University, Shanghai, China.
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Abstract
BACKGROUND It is still unclear that dissection of recurrent laryngeal nerve nodes is mandatory in patients with cT1 middle or lower thoracic esophageal squamous cell carcinoma when the nodes are negative in preoperative staging workup. We aimed to evaluate the feasibility of near-infrared image-guided lymphatic mapping of bilateral recurrent laryngeal nerve nodes. METHODS The day before operation, we injected indocyanine green (ICG) into the submucosal layer by endoscopy. At the time of upper mediastinal dissection, ICG-stained basins were identified along the bilateral recurrent laryngeal nerves and retrieved under guidance of the Firefly system. After the operation, remnant ICG-unstained basins were dissected from the specimen to assess the presence of metastasis. RESULTS Of 29 patients enrolled, ICG-stained basins could be identified in 25 patients (86.2%), and 6 of them (24.0%) had nodal metastasis; 4 in the right recurrent laryngeal nerve chain, 1 in the left recurrent laryngeal nerve chain, and 1 in both recurrent laryngeal nerve chains. On pathologic examination of 345 recurrent laryngeal nerve nodes, two metastatic nodes were identified in ICG-unstained basins along the left recurrent laryngeal nerve in a patient who had lymph node metastases in ICG-stained basins along both recurrent laryngeal nerves. Negative predictive value in detection of nodal metastasis was 100% for the right recurrent laryngeal nerve chain and 98.2% for the left recurrent laryngeal nerve chain. CONCLUSIONS Real-time assessment of recurrent laryngeal nerve nodes with near-infrared image was technically feasible, and we could detect lymphatic basins that most likely have nodal metastasis. Our technique might be useful in determining the optimal extent of lymphadenectomy.
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Du J, Li Y, Wang Q, Batchu N, Zou J, Sun C, Lv S, Song Q, Li Q. Sentinel lymph node mapping in gynecological oncology. Oncol Lett 2017; 14:7669-7675. [PMID: 29344213 PMCID: PMC5755034 DOI: 10.3892/ol.2017.7219] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2015] [Accepted: 05/18/2017] [Indexed: 01/02/2023] Open
Abstract
The intraoperative mapping of sentinel lymph nodes (SLNs) is part of the treatment strategy for a number of types of tumor. To retrospectively compare results from the mapping of pelvic SLNs for gynecological oncology, using distinct dyes, the present review was conducted to determine the clinical significance of SLN mapping for gynecological oncology. In addition, the present study aimed at identifying an improved choice for SLN mapping tracers in clinical application. Each dye exhibits demerits when applied in the clinical environment. The combination of radioisotopes and blue dyes was identified to exhibit the most accurate detection rate of SLN drainage of gynecological oncology. However, contrast agents were unable to identify whether a SLN is positive or negative for metastasis prior to pathologic examination; additional studies are required.
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Affiliation(s)
- Jiang Du
- Department of Obstetrics and Gynecology, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
| | - Yaling Li
- Gongzhuling Health Workers High School, Gongzhuling, Jilin 136100, P.R. China
| | - Qing Wang
- Department of Obstetrics and Gynecology, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
| | - Nasra Batchu
- Department of Obstetrics and Gynecology, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
| | - Junkai Zou
- Department of Obstetrics and Gynecology, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
| | - Chao Sun
- Department of Obstetrics and Gynecology, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
| | - Shulan Lv
- Department of Obstetrics and Gynecology, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
| | - Qing Song
- Department of Obstetrics and Gynecology, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
- Cardiovascular Research Institute, Morehouse School of Medicine, Atlanta, Georgia 30310, USA
- Big Data Center, First Affiliated Hospital, Xi'an Jiatong University, Xi'an, Shaanxi 710061, P.R. China
| | - Qiling Li
- Department of Obstetrics and Gynecology, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
- Big Data Center, First Affiliated Hospital, Xi'an Jiatong University, Xi'an, Shaanxi 710061, P.R. China
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Künzli HT, van Berge Henegouwen MI, Gisbertz SS, van Esser S, Meijer SL, Bennink RJ, Wiezer MJ, Seldenrijk CA, Bergman JJGHM, Weusten BLAM. Pilot-study on the feasibility of sentinel node navigation surgery in combination with thoracolaparoscopic lymphadenectomy without esophagectomy in early esophageal adenocarcinoma patients. Dis Esophagus 2017; 30:1-8. [PMID: 28881907 DOI: 10.1093/dote/dox097] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2017] [Indexed: 12/11/2022]
Abstract
High-risk submucosal esophageal adenocarcinoma's might be treated curatively by means of radical endoscopic resection, followed by thoracolaparoscopic lymphadenectomy without concomitant esophagectomy. A preclinical study has shown the feasibility and safety of this approach; however, no studies are performed in a clinical setting. In addition, sentinel node navigation surgery could be valuable in tailoring the extent of the lymphadenectomy. This study aimed to evaluate the feasibility and safety of thoracolaparoscopic lymphadenectomy without esophagectomy (phase I) and sentinel node navigation surgery (phase II) in patients with early esophageal adenocarcinoma. Patients with T1N0M0 early esophageal adenocarcinoma scheduled for esophagectomy without neoadjuvant therapy were included. Phase I: Two-field, esophagus preserving, thoracolaparoscopic lymphadenectomy was performed, followed by esophagectomy in the same session. Primary outcome parameters were the number of lymph nodes resected, and number of retained lymph nodes in the esophagectomy specimen. Phase II: A radioactive tracer was injected endoscopically the day before surgery. Static imaging was performed 15 and 120 minutes after injection. The day of surgery, sentinel node navigation surgery followed by esophagectomy was performed. Primary outcome parameters were the percentage of patients with a detectable sentinel node, and the concordance between static imaging and probe-based detection of sentinel node. Phase I: Five patients were included, and a median of 30 (IQR: 25-46) lymph nodes was resected. A median of 6 (IQR: 2-9) retained lymph nodes was found in the esophagectomy specimen. No acute adverse events occurred, but near the end of lymphadenectomy esophageal discoloration was observed, possibly indicating ischemia. Phase II: In all five included patients sentinel nodes could be visualized and resected, at a median of 3 (IQR: 2-5) locations. There was a high concordance between imaging and probe-based detection of sentinel nodes. In conclusion, sentinel node navigation surgery followed by lymphadenectomy without concomitant esophagectomy seems feasible in patients with high-risk submucosal early esophageal adenocarcinoma. More evidence is however needed before applying this technique in clinical practice.
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Affiliation(s)
- H T Künzli
- Department of Gastroenterology and Hepatology.,Department of Gastroenterology and Hepatology
| | | | | | | | | | - R J Bennink
- Department of Radiology and Nuclear Medicine, Academic Medical Center, Amsterdam, the Netherlands
| | | | - C A Seldenrijk
- Department of Pathology, Pathology-DNA, St. Antonius Hospital, Nieuwegein
| | | | - B L A M Weusten
- Department of Gastroenterology and Hepatology.,Department of Gastroenterology and Hepatology
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Abstract
Oesophageal cancer is the sixth most common cause of cancer-related death worldwide and is therefore a major global health challenge. The two major subtypes of oesophageal cancer are oesophageal squamous cell carcinoma (OSCC) and oesophageal adenocarcinoma (OAC), which are epidemiologically and biologically distinct. OSCC accounts for 90% of all cases of oesophageal cancer globally and is highly prevalent in the East, East Africa and South America. OAC is more common in developed countries than in developing countries. Preneoplastic lesions are identifiable for both OSCC and OAC; these are frequently amenable to endoscopic ablative therapies. Most patients with oesophageal cancer require extensive treatment, including chemotherapy, chemoradiotherapy and/or surgical resection. Patients with advanced or metastatic oesophageal cancer are treated with palliative chemotherapy; those who are human epidermal growth factor receptor 2 (HER2)-positive may also benefit from trastuzumab treatment. Immuno-oncology therapies have also shown promising early results in OSCC and OAC. In this Primer, we review state-of-the-art knowledge on the biology and treatment of oesophageal cancer, including screening, endoscopic ablative therapies and emerging molecular targets, and we discuss best practices in chemotherapy, chemoradiotherapy, surgery and the maintenance of patient quality of life.
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Affiliation(s)
- Elizabeth C. Smyth
- Department of Gastrointestinal Oncology, Royal Marsden Hospital, London & Sutton. United Kingdom
| | - Jesper Lagergren
- Division of Cancer Studies, King's College London, United Kingdom
- Upper Gastrointestinal Surgery, Department of Molecular medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, 17176 Stockholm, Sweden
| | | | - Florian Lordick
- University Cancer Center Leipzig, University Medicine Leipzig, Leipzig, Germany
| | - Manish A. Shah
- Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, New York-Presbyterian Hospital, New York. United States
| | - Pernilla Lagergren
- Surgical care science, Department of Molecular medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, Sweden
| | - David Cunningham
- Department of Gastrointestinal Oncology, Royal Marsden Hospital, London & Sutton. United Kingdom
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Cavallin F, Alfieri R, Scarpa M, Cagol M, Ruol A, Fassan M, Rugge M, Ancona E, Castoro C. Nodal skip metastasis in thoracic esophageal squamous cell carcinoma: a cohort study. BMC Surg 2017; 17:49. [PMID: 28464907 PMCID: PMC5414191 DOI: 10.1186/s12893-017-0247-5] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2017] [Accepted: 04/20/2017] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Nodal skip metastasis is a prognostic factor in some sites of malignancies, but its role in esophageal cancer is still unclear. The present study aimed to investigate occurrence and effect of nodal skip metastases in thoracic esophageal squamous cell carcinoma. METHODS All 578 patients undergoing esophagectomy for thoracic esophageal squamous cell carcinoma at the Center for Esophageal Diseases located in Padova between January 1992 and December 2010 were retrospectively evaluated. Selection criteria were R0 resection, pathological M0 stage and pathological lymph node involvement. Patients receiving neoadjuvant therapy were excluded. RESULTS The selection identified 88 patients with lymph node involvement confirmed by pathological evaluation. Sixteen patients (18.2%) had nodal skip metastasis. Adjusting for the number of lymph node metastases, patient with nodal skip metastasis had similar 5-year overall survival (14% vs. 13%, p = 0.93) and 5-year disease free survival (14% vs. 9%, p = 0.48) compared to patients with both peritumoral and distant lymph node metastases. The risk difference of nodal skip metastasis was: -24.1% (95% C.I. -43.1% to -5.2%) in patients with more than one lymph node metastasis compared to those with one lymph node metastasis; -2.3% (95% C.I. -29.8% to 25.2%) in middle thoracic esophagus and -23.0% (95% C.I. -47.8% to 1.8%) in lower thoracic esophagus compared to upper thoracic esophagus; 18.1% (95% C.I. 3.2% to 33.0%) in clinical N0 stage vs. clinical N+ stage. CONCLUSIONS Nodal skip metastasis is a common pattern of metastatic lymph involvement in thoracic esophageal squamous cell carcinoma. However, neither overall survival nor disease free survival are associated with nodal skip metastasis occurrence.
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Affiliation(s)
- Francesco Cavallin
- Esophageal and Digestive Tract Surgical Unit, Regional Centre for Esophageal Disease, Veneto Institute of Oncology IOV IRCCS, Padova, Italy
| | - Rita Alfieri
- Esophageal and Digestive Tract Surgical Unit, Regional Centre for Esophageal Disease, Veneto Institute of Oncology IOV IRCCS, Padova, Italy
| | - Marco Scarpa
- Esophageal and Digestive Tract Surgical Unit, Regional Centre for Esophageal Disease, Veneto Institute of Oncology IOV IRCCS, Padova, Italy
| | - Matteo Cagol
- Esophageal and Digestive Tract Surgical Unit, Regional Centre for Esophageal Disease, Veneto Institute of Oncology IOV IRCCS, Padova, Italy
| | - Alberto Ruol
- 3rd Surgical Clinic, Azienda Ospedaliera di Padova, Padova, Italy
| | - Matteo Fassan
- Department of Medicine (DIMED), Surgical Pathology & CytopathologyUnit, University of Padova, Padova, Italy
| | - Massimo Rugge
- Department of Medicine (DIMED), Surgical Pathology & CytopathologyUnit, University of Padova, Padova, Italy
| | - Ermanno Ancona
- Esophageal and Digestive Tract Surgical Unit, Regional Centre for Esophageal Disease, Veneto Institute of Oncology IOV IRCCS, Padova, Italy
| | - Carlo Castoro
- Esophageal and Digestive Tract Surgical Unit, Regional Centre for Esophageal Disease, Veneto Institute of Oncology IOV IRCCS, Padova, Italy
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Künzli HT, van Berge Henegouwen M, Gisbertz S, Seldenrijk C, Kuijpers K, Bergman J, Wiezer M, Weusten B. Thoracolaparoscopic dissection of esophageal lymph nodes without esophagectomy is feasible in human cadavers and safe in a porcine survival study. Dis Esophagus 2016; 29:649-55. [PMID: 26228037 DOI: 10.1111/dote.12395] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
High-risk early esophageal adenocarcinoma (i.e. submucosal invasion >500 nm, poor differentiation, and/or presence of lymphovascular invasion) is currently treated with esophagectomy with lymph node (LN) dissection given the high rates of LN metastases. However, esophagectomy is associated with substantial morbidity and mortality. Endoscopic radical resection followed by thoracolaparoscopic LN dissection without concomitant esophagectomy could be an alternative. The study aim was to evaluate the feasibility and safety of thoracolaparoscopic dissection of esophageal LNs in a preclinical setting. (i) In human cadavers, thoracolaparoscopic dissection of LNs involved in drainage of the esophagus was performed. Subsequently, esophagectomy was performed to be able to detect retained LNs. Outcome parameters included the number of dissected LNs, the number of retained LNs in the esophagectomy specimen (ES), and technical success. (ii) In swine, thoracolaparoscopic LN dissection was also performed. After the procedure, the swine survived for 28 days. Thereafter, the swine were sacrificed and esophagectomy was performed. Outcome parameters included the presence of ischemia and/or stenosis in the ES and other complications. (i) In five human cadavers, a median of 26 LNs (interquartile range 22-46) were dissected. In two ES, one retained LN was found: one high paraesophageal, one low paraesophageal. Technical success rate was 100%. (ii) None of the seven porcine ES showed signs of ischemia or stenosis. One swine died because of ventricular fibrillation during surgery; during follow up no complications were observed. Thoracolaparoscopic dissection of LNs involved in the drainage of the esophagus is feasible in human cadavers and swine. The porcine survival study suggests that the esophageal vascularity is not severely compromised by the procedure. As anatomy differs between swine and humans, safety of the procedure will have to be investigated thoroughly before applying this new technique as the treatment of choice.
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Affiliation(s)
- H T Künzli
- Department of Gastroenterology and Hepatology, St. Antonius Hospital, Nieuwegein, The Netherlands
- Department of Gastroenterology and Hepatology, Academic Medical Center Amsterdam, Amsterdam, The Netherlands
| | | | - S Gisbertz
- Department of Surgery, Academic Medical Center Amsterdam, Amsterdam, The Netherlands
| | - C Seldenrijk
- Department of Pathology, St. Antonius Hospital, Nieuwegein, The Netherlands
| | - K Kuijpers
- Department of Pathology, St. Antonius Hospital, Nieuwegein, The Netherlands
| | - J Bergman
- Department of Gastroenterology and Hepatology, Academic Medical Center Amsterdam, Amsterdam, The Netherlands
| | - M Wiezer
- Department of Surgery, St. Antonius Hospital, Nieuwegein, The Netherlands
| | - B Weusten
- Department of Gastroenterology and Hepatology, St. Antonius Hospital, Nieuwegein, The Netherlands
- Department of Gastroenterology and Hepatology, Academic Medical Center Amsterdam, Amsterdam, The Netherlands
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11
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Goense L, van Rossum PSN, Kandioler D, Ruurda JP, Goh KL, Luyer MD, Krasna MJ, van Hillegersberg R. Stage-directed individualized therapy in esophageal cancer. Ann N Y Acad Sci 2016; 1381:50-65. [PMID: 27384385 DOI: 10.1111/nyas.13113] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2016] [Accepted: 05/05/2016] [Indexed: 12/16/2022]
Abstract
Esophageal cancer is the eighth most common cancer worldwide, and the incidence of esophageal carcinoma is rapidly increasing. With the advent of new staging and treatment techniques, esophageal cancer can now be managed through various strategies. A good understanding of the advances and limitations of new staging techniques and how these can guide in individualizing treatment is important to improve outcomes for esophageal cancer patients. This paper outlines the recent progress in staging and treatment of esophageal cancer, with particularly attention to endoscopic techniques for early-stage esophageal cancer, multimodality treatment for locally advanced esophageal cancer, assessment of response to neoadjuvant treatment, and the role of cervical lymph node dissection. Furthermore, advances in robot-assisted surgical techniques and postoperative recovery protocols that may further improve outcomes after esophagectomy are discussed.
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Affiliation(s)
- Lucas Goense
- Department of Surgery, University Medical Center Utrecht, Utrecht, the Netherlands.,Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Peter S N van Rossum
- Department of Surgery, University Medical Center Utrecht, Utrecht, the Netherlands.,Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Daniela Kandioler
- Department of Surgery, Medical University of Vienna, Vienna, Austria
| | - Jelle P Ruurda
- Department of Surgery, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Khean-Lee Goh
- Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Misha D Luyer
- Department of Surgery, Catharina Hospital Eindhoven, Eindhoven, the Netherlands
| | - Mark J Krasna
- Meridian Cancer Care, Jersey Shore University Medical Center, Neptune, New Jersey
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Takeuchi H, Kawakubo H, Nakamura R, Fukuda K, Takahashi T, Wada N, Kitagawa Y. Clinical Significance of Sentinel Node Positivity in Patients with Superficial Esophageal Cancer. World J Surg 2016; 39:2941-7. [PMID: 26296842 DOI: 10.1007/s00268-015-3217-z] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND Sentinel node (SN) mapping in esophageal cancer has been reported to be technically feasible with an acceptable detection rate and accuracy. However, the clinical significance and survival analysis findings associated with the metastatic status of SNs in patients with early-stage esophageal cancer have not been clarified. In this study, we investigated the clinical significance and survival impact of SN mapping in early-stage esophageal cancer. METHODS Among patients who were diagnosed preoperatively with clinical T1N0M0 or T2N0M0 esophageal cancer and who underwent SN mapping, 70 consecutive patients who were diagnosed with pathological T1 primary thoracic esophageal cancer were enrolled in this study. Sixty-four (91 %) patients were diagnosed with squamous cell carcinoma while 5 (7 %) patients were with adenocarcinoma. Endoscopic injection of technetium-99m tin colloid was performed before surgery, and radioactive SNs were identified by preoperative lymphoscintigraphy and intraoperative gamma probing. Standard esophagectomy with lymphadenectomy was performed in all patients, and all resected nodes were evaluated by routine pathological examination. RESULTS SNs were successfully detected in 65 (92.9 %) of 70 patients with pT1 esophageal cancer. The sensitivity to predict lymph node metastasis was 91.7 %, and the diagnostic accuracy based on SN status was 96.9 %. Although there was a wide distribution of SNs from cervical to abdominal areas, 84.5 % of the patients had no lymph node metastasis or had lymph node metastasis only in SN. The disease-specific survival of the patients with metastatic non-SNs was significantly worse relative to that of the patients with no lymph node metastasis or lymph node metastasis only in SN. CONCLUSIONS This study demonstrated that radio-guided SN mapping is useful not only as an accurate diagnostic tool for detecting lymph node metastasis but also as a tool for prognostic stratification in patients with cN0 early esophageal cancer.
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Affiliation(s)
- Hiroya Takeuchi
- Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
| | - Hirofumi Kawakubo
- Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Rieko Nakamura
- Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Kazumasa Fukuda
- Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Tsunehiro Takahashi
- Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Norihito Wada
- Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Yuko Kitagawa
- Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
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Boone J, Hobbelink MGG, Schipper MEI, Vleggaar FP, Borel Rinkes IHM, de Haas RJ, Ruurda JP, van Hillegersberg R. Sentinel node biopsy during thoracolaparoscopic esophagectomy for advanced esophageal cancer. World J Surg Oncol 2016; 14:117. [PMID: 27094390 PMCID: PMC4837514 DOI: 10.1186/s12957-016-0866-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2016] [Accepted: 04/12/2016] [Indexed: 02/01/2023] Open
Abstract
Background Omitting extensive lymph node dissection could reduce esophagectomy morbidity in patients without lymph node metastases. Sentinel node biopsy may identify abdominal or thoracic lymph node metastases, thereby differentiating treatment. Feasibility of this approach was investigated in Western European esophageal cancer patients with advanced disease, without lymph node metastases at diagnostic work-up. Methods The sentinel node biopsy was performed in eight esophageal cancer patients with cT1-3N0 disease. One day pre-operatively, Tc-99m-labeled nanocolloid was endoscopically injected around the tumor. Lymphoscintigraphy was performed 1 and 3 h after injection. All patients underwent robotic thoracolaparoscopic esophagectomy with two-field lymph node dissection. Intraoperatively, sentinel nodes were detected by gamma probe. The resection specimen was analyzed for remaining activity by scintigraphy and gamma probe. Results Visualization rates of lymphoscintigraphy 1 and 3 h after tracer injection were 88 and 100 %, respectively. Intraoperative identification rate was 38 %. Postoperative identification was possible in all patients using the gamma probe to analyze the resection specimen. In 5/8 patients, lymph node metastases were found at histopathology, none of which was detected by the sentinel node biopsy. No adverse events related to the sentinel node biopsy were observed. Conclusions In our advanced esophageal cancer patients who underwent thoracolaparoscopic esophagectomy, the sentinel node biopsy did not predict lymph node status. Probably the real sentinel node could not be identified due to localization adjacent to the primary tumor or bypassing due to metastatic tumor involvement. Therefore, we consider the sentinel node biopsy not feasible in advanced esophageal cancer.
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Affiliation(s)
- Judith Boone
- Department of Surgery (G04.228), University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands
| | - Monique G G Hobbelink
- Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands
| | - Marguerite E I Schipper
- Department of Pathology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands
| | - Frank P Vleggaar
- Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands
| | - Inne H M Borel Rinkes
- Department of Surgery (G04.228), University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands
| | - Robbert J de Haas
- Department of Surgery (G04.228), University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands
| | - Jelle P Ruurda
- Department of Surgery (G04.228), University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands
| | - Richard van Hillegersberg
- Department of Surgery (G04.228), University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.
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Matsuda T, Takeuchi H, Tsuwano S, Nakahara T, Mukai M, Kitagawa Y. Sentinel node mapping in adenocarcinoma of the esophagogastric junction. World J Surg 2015; 38:2337-44. [PMID: 24752362 DOI: 10.1007/s00268-014-2573-4] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
BACKGROUND The incidence of adenocarcinoma of the esophagogastric junction (AEG) is increasing, but the surgical strategy for AEG remains controversial. We hypothesized that sentinel node (SN) mapping for AEG could be validated to avoid unnecessary lymphadenectomy and permit minimally invasive surgery. We examined the feasibility of SN mapping for AEG. METHODS We enrolled 15 patients with preoperatively diagnosed cT1 N0 M0 primary AEG (Siewert type I, N = 3; Siewert type II, N = 12) lesions measuring <4 cm in diameter. The dual tracer method employing radioactive colloid and blue dye was used to detect SNs. The distribution of SNs was compared with that of metastatic lymph nodes in 52 patients who were surgically treated without SN mapping. RESULTS SNs were successfully identified in all the patients. Two patients with lymph node metastasis had positive SNs identified via an intraoperative pathological examination, and the diagnostic sensitivity and accuracy based on the SN status were both 100 %. For Siewert type II AEG, the SNs were not detected in the lower mediastinum by intraoperative gamma probing. Thus, all surgical procedures were performed via a transhiatal approach. No patient without SN metastasis experienced cancer recurrence during a 38-month median follow-up. The distribution of SNs was similar to that of lymph node metastasis in the patients who were surgically treated without SN mapping. CONCLUSIONS We achieved 100 % SN detection. Our results suggested that SN mapping is feasible for AEG and highly sensitive and accurate in diagnosing lymph node metastasis. SN mapping may clarify the necessity of mediastinal lymph node dissection and individualize minimally invasive surgery.
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Affiliation(s)
- Tatsuo Matsuda
- Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
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Rosso KJ, Nathanson SD. Techniques that accurately identify the sentinel lymph node in cancer. World J Surg Proced 2015; 5:14-26. [DOI: 10.5412/wjsp.v5.i1.14] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2014] [Revised: 12/30/2014] [Accepted: 02/09/2015] [Indexed: 02/06/2023] Open
Abstract
Sentinel lymph node (SLN) biopsy has become the gold standard for patients with melanoma and breast cancer but it’s clinical application in other solid tumor types such as cancers of the esophagus, stomach, colon and rectum, head and neck, penis, uterine cervix and endometrium has been somewhat limited. Commonly used mapping techniques utilizing the combination of radiocolloid and blue dye may result in reduced SLN detection and increased false negative rates when applied to cancers with more complex lymphatic drainage patterns. Novel localization techniques including near infrared fluorescence, high resolution imaging and molecular targeted agents have been developed to address the limitations of conventional SLN detection practices in many solid tumor types. This article reviews the indications, techniques and detection rates for SLN biopsy in several different solid tumor types as well as the promising novel techniques created to address the contemporary limitations of this procedure.
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Tausch C, Baege A, Rageth C. Mapping lymph nodes in cancer management - role of (99m)Tc-tilmanocept injection. Onco Targets Ther 2014; 7:1151-8. [PMID: 25028560 PMCID: PMC4077853 DOI: 10.2147/ott.s50394] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
Two decades ago, lymphatic mapping of sentinel lymph nodes (SLN) was introduced into surgical cancer management and was termed sentinel node navigated surgery. Although this technique is now routinely performed in the management of breast cancer and malignant melanoma, it is still under investigation for use in other cancers. The radioisotope technetium (99mTc) and vital blue dyes are among the most widely used enhancers for SLN mapping, although near-infrared fluorescence imaging of indocyanine green is also becoming more commonly used. 99mTc-tilmanocept is a new synthetic radioisotope with a relatively small molecular size that was specifically developed for lymphatic mapping. Because of its small size, 99mTc-tilmanocept quickly migrates from its site of injection and rapidly accumulates in the SLN. The mannose moieties of 99mTc-tilmanosept facilitate its binding to mannose receptors (CD206) expressed in reticuloendothelial cells of the SLN. This binding prevents transit to second-echelon lymph nodes. In Phase III trials of breast cancer and malignant melanoma, and Phase II trials of other malignancies, 99mTc-tilmanocept had superior identification rates and sensitivity compared with blue dye. Trials comparing 99mTc-tilmanocept with other 99mTc-based agents are required before it can be routinely used in clinical settings.
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Chen XZ, Zhang WH, Hu JK. Lymph node metastasis and lymphadenectomy of resectable adenocarcinoma of the esophagogastric junction. Chin J Cancer Res 2014; 26:237-242. [PMID: 25035648 PMCID: PMC4076724 DOI: 10.3978/j.issn.1000-9604.2014.06.17] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2014] [Accepted: 06/12/2014] [Indexed: 02/05/2023] Open
Abstract
Based on Siewert classification, adenocarcinomas of the esophagogastric junction (AEGs) have different behaviors of perigastric-mediastinal nodal metastasis. Siewert type I AEGs have higher incidence of mediastinal nodal metastasis than those of type II or III, especially at middle-upper mediastinum. With regard to the necessity of mediastinal lymphadenectomy, theoretically, transthoracic esophagogastrectomy with complete mediastinal lymphadenectomy is suggested for Siewert type I AEGs, while transhiatal total gastrectomy with lower mediastinal and D2 perigastric lymphadenectomy is a standard surgery for type II-III AEGs. Nevertheless, the mediastinal nodal metastasis is an independent factor of poor prognosis for any type of AEG.
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Affiliation(s)
- Xin-Zu Chen
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Wei-Han Zhang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Jian-Kun Hu
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
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