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Tkachev S, Brosalov V, Kit O, Maksimov A, Goncharova A, Sadyrin E, Dalina A, Popova E, Osipenko A, Voloshin M, Karnaukhov N, Timashev P. Unveiling Another Dimension: Advanced Visualization of Cancer Invasion and Metastasis via Micro-CT Imaging. Cancers (Basel) 2025; 17:1139. [PMID: 40227647 PMCID: PMC11988112 DOI: 10.3390/cancers17071139] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Revised: 03/19/2025] [Accepted: 03/20/2025] [Indexed: 04/15/2025] Open
Abstract
Invasion and metastasis are well-known hallmarks of cancer, with metastatic disease accounting for 60% to 90% of cancer-related deaths [...].
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Affiliation(s)
- Sergey Tkachev
- Institute for Regenerative Medicine, Sechenov University, 119992 Moscow, Russia
| | | | - Oleg Kit
- National Medical Research Centre for Oncology, 344037 Rostov-on-Don, Russia
| | - Alexey Maksimov
- National Medical Research Centre for Oncology, 344037 Rostov-on-Don, Russia
| | - Anna Goncharova
- National Medical Research Centre for Oncology, 344037 Rostov-on-Don, Russia
| | - Evgeniy Sadyrin
- Laboratory of Mechanics of Biocompatible Materials, Don State Technical University, 344003 Rostov-on-Don, Russia
| | - Alexandra Dalina
- Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119334 Moscow, Russia
| | - Elena Popova
- Federal Research and Clinical Center of Specialized Medical Care and Medical Technologies, 115682 Moscow, Russia
| | - Anton Osipenko
- Department of Pharmacology, Siberian State Medical University, 634050 Tomsk, Russia
| | - Mark Voloshin
- A.S. Loginov Moscow Clinical Scientific Center, 111123 Moscow, Russia
| | - Nikolay Karnaukhov
- A.S. Loginov Moscow Clinical Scientific Center, 111123 Moscow, Russia
- Institute of Clinical Morphology and Digital Pathology, Sechenov University, 119991 Moscow, Russia
| | - Peter Timashev
- Institute for Regenerative Medicine, Sechenov University, 119992 Moscow, Russia
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Chan MW, Nieuwenhuis EA, Meijer SL, Jansen M, Vieth M, van Berge Henegouwen MI, Pouw RE. Reassessment reveals underestimation of infiltration depth in surgical resection specimens with lymph-node positive T1b esophageal adenocarcinoma. Endosc Int Open 2025; 13:a25097208. [PMID: 40007654 PMCID: PMC11855241 DOI: 10.1055/a-2509-7208] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Accepted: 12/16/2024] [Indexed: 02/27/2025] Open
Abstract
Background and study aims Endoscopic resection (ER) has proven effective and safe for T1 esophageal adenocarcinoma (EAC). However, uncertainty remains concerning risk-benefit return of esophagectomy for submucosal lesions (T1b). Surgical series in past decades have reported significant risk of lymph node metastasis (LNM) in T1b EAC, but these rates may be overestimated due to limitations in histological assessment of surgical specimens. We aimed to test this hypothesis by reassessing histological risk features in surgical specimens from T1b EAC cases with documented LNM. Patients and methods A retrospective cross-sectional study (1994-2005) was conducted. Patients who underwent direct esophagectomy without prior neoadjuvant therapy for suspected T1b EAC with LNM were included. Additional tissue sections were prepared from archival tumor blocks. A consensus diagnosis on tumor depth, differentiation grade, and lymphovascular invasion (LVI) was established by a panel of experienced pathologists. Results Specific depth of submucosal invasion (sm1 to sm3) was not specified in 10 of 11 archival case sign-out reports. LVI status was not reported in seven of 11 cases. Following reassessment, one patient was found to have deep tumor invasion into the muscularis propria (T2). The remaining 10 of 11 patients exhibited deep submucosal invasion (sm2-3), with five showing one or more additional risk features (poor differentiation and/or LVI). Conclusions Our findings highlight the potential for underestimating tumor depth of invasion and other high-risk features in surgical specimens. Despite the limited cohort size, our study confirmed a consistent high-risk histological profile across all cases. Caution is warranted when extrapolating LNM risk data from historic heterogeneous cross-sectional surgical cohorts to the modern ER era.
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Affiliation(s)
- Man Wai Chan
- Gastroenterology and Hepatology, Cancer Center Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC Locatie VUmc, Amsterdam, Netherlands
| | - Esther A. Nieuwenhuis
- Gastroenterology and Hepatology, Cancer Center Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC Locatie VUmc, Amsterdam, Netherlands
| | - Sybren L Meijer
- Pathology, Amsterdam UMC Locatie AMC, Amsterdam, Netherlands
| | - Marnix Jansen
- Pathology, University College London Hospitals NHS Foundation Trust, London, United Kingdom of Great Britain and Northern Ireland
- University College London Cancer Institute, London, United Kingdom of Great Britain and Northern Ireland
| | - Michael Vieth
- Histopathology, Klinikum Bayreuth GmbH, Bayreuth, Germany
| | | | - R. E. Pouw
- Gastroenterology and Hepatology, Cancer Center Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC Locatie VUmc, Amsterdam, Netherlands
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Raja S, Rice TW, Lu M, Semple ME, Toth AJ, Blackstone EH, Murthy SC, Ahmad U, McNamara M, Ishwaran H. Adjuvant Therapy after Esophagectomy for Esophageal Cancer: Who Needs It?: Multi-institution Worldwide Observational Study. ANNALS OF SURGERY OPEN 2024; 5:e497. [PMID: 39711652 PMCID: PMC11661710 DOI: 10.1097/as9.0000000000000497] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Accepted: 08/21/2024] [Indexed: 12/24/2024] Open
Abstract
Objective Based on current practice guidelines, we hypothesized that most patients with esophageal cancer, particularly those with locally advanced cancer, would benefit from adjuvant therapy after esophagectomy versus esophagectomy alone. We sought to obtain a granular estimate of patient-level risk-adjusted survival for each therapeutic option by cancer histopathology and stage. Background Although esophagectomy alone is now an uncommon therapy for treating locally advanced esophageal cancer, the value of adjuvant therapy after esophagectomy is unknown. Methods From 1970 to 2014, 22,123 consecutive patients from 33 centers on 6 continents (Worldwide Esophageal Cancer Collaboration) were diagnosed with biopsy-proven adenocarcinoma (n = 7526) or squamous cell carcinoma (n = 5625), of whom 10,873 received esophagectomy alone and 2278 additional adjuvant therapy. Random forests for survival and virtual-twin analyses were performed for all-cause mortality. Results For adenocarcinoma, adjuvant therapy was beneficial only in pT4NanyM0 cancers (6-8 month survival benefit) and in pTanyN3M0 cancers (4-8 month benefit); a survival decrement was observed in pT1-3N0M0 cancers, with no effect on TanyN1-2M0 cancers. In squamous cell carcinoma, there was a 4 to 21 month survival benefit for pT3-4N0M0 cancers and a 4 to 15 month survival benefit for pT2-4N1-3M0 cancers. Conclusions Adjuvant therapy after esophagectomy appears to benefit most patients with node-positive squamous cell carcinoma, but for adenocarcinoma, its value is limited to deep cancers and to those with substantial nodal burden. Future studies of the role of adjuvant therapies should treat these 2 cancers differently, with guidelines reflecting the histopathologic-appropriate survival value of adjuvant therapy.
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Affiliation(s)
- Siva Raja
- From the Department of Thoracic and Cardiovascular Surgery, Heart, Vascular, and Thoracic Institute, Cleveland Clinic, Cleveland, OH
| | - Thomas W. Rice
- From the Department of Thoracic and Cardiovascular Surgery, Heart, Vascular, and Thoracic Institute, Cleveland Clinic, Cleveland, OH
| | - Min Lu
- Division of Biostatistics, Department of Public Health Sciences, University of Miami, Miami, FL
| | - Marie E. Semple
- Lerner Research Institute, Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH
| | - Andrew J. Toth
- Lerner Research Institute, Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH
| | - Eugene H. Blackstone
- From the Department of Thoracic and Cardiovascular Surgery, Heart, Vascular, and Thoracic Institute, Cleveland Clinic, Cleveland, OH
- Lerner Research Institute, Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH
| | - Sudish C. Murthy
- From the Department of Thoracic and Cardiovascular Surgery, Heart, Vascular, and Thoracic Institute, Cleveland Clinic, Cleveland, OH
| | - Usman Ahmad
- From the Department of Thoracic and Cardiovascular Surgery, Heart, Vascular, and Thoracic Institute, Cleveland Clinic, Cleveland, OH
| | - Michael McNamara
- Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH
| | - Hemant Ishwaran
- Division of Biostatistics, Department of Public Health Sciences, University of Miami, Miami, FL
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Nguyen CL, Tovmassian D, Isaacs A, Falk GL. Risk of lymph node metastasis in T1 esophageal adenocarcinoma: a meta-analysis. Dis Esophagus 2024; 37:doae012. [PMID: 38391209 DOI: 10.1093/dote/doae012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2023] [Revised: 06/29/2023] [Accepted: 02/02/2024] [Indexed: 02/24/2024]
Abstract
Patients with early (T1) esophageal adenocarcinoma (EAC) are increasingly having definitive local therapy endoscopically. Endoscopic resection is not able to pathologically stage or treat lymph node metastasis (LNM). Accurate identification of patients having nodal metastasis is critical to select endoscopic therapy over surgery. This study aimed to define the risk of LNM in T1 EAC. A meta-analysis of studies of patients who underwent surgery and lymphadenectomy with assessment of LNM was performed according to PRISMA. Main outcome was probability of LNM in T1a and T1b disease. Secondary outcomes were risk factors for LNM and rate of LNM in submucosal T1b (SM1, SM2, and SM3) disease. Registered with PROSPERO (CRD42022341794). Twenty cohort studies involving 2264 patients with T1 EAC met inclusion criteria: T1a (857 patients) with 36 (4.2%) node positive and T1b (1407 patients) with 327 (23.2%) node positive. Subgroup analysis of T1b lesions was available in 10 studies (405 patients). Node positivity for SM1, SM2, and SM3 was 16.3%, 16.2%, and 29.4%, respectively. T1 substage (odds ratio [OR] 7.72, 95% confidence interval [CI] 4.45-13.38, P < 0.01), tumor differentiation (OR 2.82, 95% CI 2.06-3.87, P < 0.01), and lymphovascular invasion (OR 13.65, 95% CI 6.06-30.73, P < 0.01) were associated with LNM. T1a disease demonstrated a 4.2% nodal metastasis rate and T1b disease a rate of 23.2%. Endoscopic therapy should be reserved for T1a disease and perhaps select T1b disease, which has a moderately high rate of nodal metastasis. There were inadequate data to stratify T1b SM disease into 'low-risk' and 'high-risk' based on tumor differentiation and lymphovascular invasion.
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Affiliation(s)
- Chu Luan Nguyen
- Department of Upper Gastrointestinal Surgery, Concord Repatriation General Hospital, Concord, NSW, Australia
- Department of Surgery, The University of Sydney, Camperdown, NSW, Australia
| | - David Tovmassian
- Department of Upper Gastrointestinal Surgery, Concord Repatriation General Hospital, Concord, NSW, Australia
- Department of Surgery, The University of Sydney, Camperdown, NSW, Australia
| | - Anna Isaacs
- Department of Upper Gastrointestinal Surgery, Concord Repatriation General Hospital, Concord, NSW, Australia
- Department of Surgery, The University of Sydney, Camperdown, NSW, Australia
| | - Gregory L Falk
- Department of Upper Gastrointestinal Surgery, Concord Repatriation General Hospital, Concord, NSW, Australia
- Department of Surgery, The University of Sydney, Camperdown, NSW, Australia
- Sydney Heartburn Clinic, Lindfield, NSW, Australia
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Ebert MP, Fischbach W, Hollerbach S, Höppner J, Lorenz D, Stahl M, Stuschke M, Pech O, Vanhoefer U, Porschen R. S3-Leitlinie Diagnostik und Therapie der Plattenepithelkarzinome und Adenokarzinome des Ösophagus. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:535-642. [PMID: 38599580 DOI: 10.1055/a-2239-9802] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/12/2024]
Affiliation(s)
- Matthias P Ebert
- II. Medizinische Klinik, Medizinische Fakultät Mannheim, Universitätsmedizin, Universität Heidelberg, Mannheim
- DKFZ-Hector Krebsinstitut an der Universitätsmedizin Mannheim, Mannheim
- Molecular Medicine Partnership Unit, EMBL, Heidelberg
| | - Wolfgang Fischbach
- Deutsche Gesellschaft zur Bekämpfung der Krankheiten von Magen, Darm und Leber sowie von Störungen des Stoffwechsels und der Ernährung (Gastro-Liga) e. V., Giessen
| | | | - Jens Höppner
- Klinik für Allgemeine Chirurgie, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Lübeck
| | - Dietmar Lorenz
- Chirurgische Klinik I, Allgemein-, Viszeral- und Thoraxchirurgie, Klinikum Darmstadt, Darmstadt
| | - Michael Stahl
- Klinik für Internistische Onkologie und onkologische Palliativmedizin, Evang. Huyssensstiftung, Evang. Kliniken Essen-Mitte, Essen
| | - Martin Stuschke
- Klinik und Poliklinik für Strahlentherapie, Universitätsklinikum Essen, Essen
| | - Oliver Pech
- Klinik für Gastroenterologie und Interventionelle Endoskopie, Krankenhaus Barmherzige Brüder, Regensburg
| | - Udo Vanhoefer
- Klinik für Hämatologie und Onkologie, Katholisches Marienkrankenhaus, Hamburg
| | - Rainer Porschen
- Gastroenterologische Praxis am Kreiskrankenhaus Osterholz, Osterholz-Scharmbeck
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Leclercq P, Bisschops R, Bergman JJGHM, Pouw RE. Management of high risk T1 esophageal adenocarcinoma following endoscopic resection. Best Pract Res Clin Gastroenterol 2024; 68:101882. [PMID: 38522880 DOI: 10.1016/j.bpg.2024.101882] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2023] [Accepted: 01/17/2024] [Indexed: 03/26/2024]
Abstract
High-risk T1 esophageal adenocarcinoma (HR-T1 EAC) is defined as T1 cancer, with one or more of the following histological criteria: submucosal invasion, poorly or undifferentiated cancer, and/or presence of lympho-vascular invasion. Esophagectomy has long been the only available treatment for these HR-T1 EACs and was considered necessary because of a presumed high risk of lymph node metastases up to 46%. However, endoscopic submucosal disscection have made it possible to radically remove HR-T1 EAC, irrespective of size, while leaving the esophageal anatomy intact. Parallel to this development, new publications demonstrated that the risk of lymph node metastases for HR-T1 EAC may be even <24%. Therefore, indications for endoscopic treatment of HR-T1 EAC are being reconsidered and current research aims at finding the optimal management strategy for this indication, where watchful waiting may proof to be an acceptable strategy in selected patients. In this review, we will discuss the latest developments in this field.
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Affiliation(s)
- Philippe Leclercq
- Departement of Gastroenterology, Universitair Ziekenhuis Leuven, 49 Herestraat, 3000, LEUVEN, Belgium.
| | - Raf Bisschops
- Departement of Gastroenterology, Universitair Ziekenhuis Leuven, 49 Herestraat, 3000, LEUVEN, Belgium.
| | - Jacques J G H M Bergman
- Dept. of Gastroenterology and Hepatology, Amsterdam University Medical Centers, De Boelelaan 1117, Amsterdam, 1081, HV, Netherlands.
| | - Roos E Pouw
- Dept. of Gastroenterology and Hepatology, Amsterdam University Medical Centers, De Boelelaan 1117, Amsterdam, 1081, HV, Netherlands.
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Abou Chaar MK, Godin A, Harmsen WS, Wzientek C, Saddoughi SA, Hallemeier CL, Cassivi SD, Nichols FC, Reisenauer JS, Shen KR, Tapias LF, Wigle DA, Blackmon SH. Determinants of Long-term Survival Decades After Esophagectomy for Esophageal Cancer. Ann Thorac Surg 2023; 116:1036-1044. [PMID: 37353102 DOI: 10.1016/j.athoracsur.2023.05.033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Revised: 03/26/2023] [Accepted: 05/01/2023] [Indexed: 06/25/2023]
Abstract
BACKGROUND Long-term survival in esophagectomy patients with esophageal cancer is low due to tumor-related characteristics, with few reports of modifiable variables influencing outcome. We identified determinants of overall survival, time to recurrence, and disease-free survival in this patient cohort. METHODS Adult patients who underwent esophagectomy for primary esophageal cancer from January 5, 2000, through December 30, 2010, at our institution were identified. Univariate Cox models and multivariable logistic regression analyses were used to identify associations between modifiable and unmodifiable patient and clinical variables and outcome of survival for the total cohort and a subgroup with locally advanced disease. RESULTS We identified 870 patients with esophageal cancer who underwent esophagectomy. The median follow-up time was 15 years, and the 15-year overall survival rate was 25.2%, survival free of recurrence was 57.96%, and disease-free survival was 24.21%. Decreased overall survival was associated with the following unmodifiable variables: older age, male sex, active smoking status, history of coronary artery disease, advanced clinical stage, and tumor location. Decreased overall survival was associated with the following modifiable variables: use of neoadjuvant therapy, advanced pathologic stage, resection margin positivity, surgical reintervention, and blood transfusion requirement. The overall survival probability 6 years after esophagectomy was 0.920 (95% CI, 0.895-0.947), and time-to-recurrence probability was 0.988 (95% CI, 0.976-1.000), with a total of 17 recurrences and 201 deaths. CONCLUSIONS Once patients survive 5 years, recurrence is rare. Long-term survival can be achieved in high-volume centers adhering to National Comprehensive Cancer Network guidelines using multidisciplinary care teams that is double what has been previously reported in the literature from national databases.
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Affiliation(s)
- Mohamad K Abou Chaar
- Department of Surgery, Mayo Clinic School of Graduate Medical Education, Mayo Clinic College of Medicine and Science, Rochester, Minnesota
| | - Anny Godin
- Division of Thoracic Surgery, Mayo Clinic, Rochester, Minnesota
| | - William S Harmsen
- Division of Clinical Trials and Biostatistics, Mayo Clinic, Rochester, Minnesota
| | - Camryn Wzientek
- Division of Thoracic Surgery, Mayo Clinic, Rochester, Minnesota
| | | | | | | | | | | | - K Robert Shen
- Division of Thoracic Surgery, Mayo Clinic, Rochester, Minnesota
| | - Luis F Tapias
- Division of Thoracic Surgery, Mayo Clinic, Rochester, Minnesota
| | - Dennis A Wigle
- Division of Thoracic Surgery, Mayo Clinic, Rochester, Minnesota
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Fernandes A, Li C, French D, Ellsmere J. Ten-year follow-up of endoscopic mucosal resection versus esophagectomy for esophageal intramucosal adenocarcinoma in the setting of Barrett's esophagus: a Canadian experience. Surg Endosc 2023; 37:8735-8741. [PMID: 37563345 DOI: 10.1007/s00464-023-10318-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Accepted: 07/19/2023] [Indexed: 08/12/2023]
Abstract
BACKGROUND Endoscopic mucosal resection (EMR) is an effective treatment for esophageal intramucosal adenocarcinoma (IMC), with similar recurrence and mortality rates versus esophagectomy in up to 5 years of follow-up. Long-term outcomes to 10 years have not been studied. This retrospective study investigates IMC eradication, recurrence, morbidity and mortality at 10 years following EMR versus esophagectomy in a single Canadian institution. METHODS Patients with IMC treated via esophagectomy or EMR from 2006 to 2015 were included. Post-EMR endoscopic follow-up occurred every 3 months for 1 year, every 6 months for 2 years and every 12 months thereafter. Categorical variables were expressed as percentages and continuous variables as mean with standard deviation or median and interquartile range. The student's t-test and Fischer's exact test were used for comparisons. Survival analysis utilized the Kaplan-Meier estimator and log-rank test. RESULTS Twenty-four patients were included. Patient and tumor characteristics were similar between groups. Median follow-up for EMR and esophagectomy were 85.2 months [IQR 64.8] and 126 months [IQR 54] respectively. A mean of 1.3 EMR (SD 1.1) were required for eradication, which was seen in 12 patients (12/14, 86%). No EMR-related complications occurred. Disease progression was seen in two patients (2/14, 14%); local recurrence was seen in 1 patient (1/14, 7%). Esophagectomy eradicated IMC in 10 patients (10/10, 100%); recurrence was seen in 2 (2/10, 20%, metastatic). Major, early esophagectomy-related morbidity affected 3 patients (3/10, 30%), and late morbidity was documented for 9 (9/10, 90%). Esophagectomy and EMR had similar recurrence rates (p = 0.554). Esophagectomy was associated with significantly more procedure-related morbidity (p < 0.001). There was no difference in mortality (p = 0.442) or disease-free survival (p = 0.512) between treatment groups. CONCLUSION EMR and esophagectomy for the treatment of IMC are associated with comparable recurrence rates and disease-free survival in 10-year follow-up. EMR is associated with significantly lower procedure-associated morbidity. EMR can be used to treat T1a distal esophageal adenocarcinoma with minimal procedure-related morbidity, and acceptable oncologic outcomes in long-term follow-up.
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Affiliation(s)
- Alisha Fernandes
- Division of General and Gastrointestinal Surgery, Department of Surgery, Dalhousie University, Room 8-23/4 Victoria Building, QEII-HSC, VG Site, 1276 South Park St, Halifax, NS, B3H 2Y9, Canada
| | - Chao Li
- Division of General Surgery, Department of Surgery, Centre Intégré Universitaire de Santé et de Services Sociaux de l'Est-de-l'Île-de-Montréal, Montreal, Canada
| | - Daniel French
- Division of Thoracic Surgery, Department of Surgery, Dalhousie University, Halifax, Canada
| | - James Ellsmere
- Division of General and Gastrointestinal Surgery, Department of Surgery, Dalhousie University, Room 8-23/4 Victoria Building, QEII-HSC, VG Site, 1276 South Park St, Halifax, NS, B3H 2Y9, Canada.
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Raja S, Rice TW, Lu M, Semple ME, Blackstone EH, Murthy SC, Ahmad U, McNamara M, Toth AJ, Hemant I, Worldwide Esophageal Cancer Collaboration Investigators. Adjuvant Therapy After Neoadjuvant Therapy for Esophageal Cancer: Who Needs It? Ann Surg 2023; 278:e240-e249. [PMID: 35997269 PMCID: PMC10955553 DOI: 10.1097/sla.0000000000005679] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE We hypothesized that, on average, patients do not benefit from additional adjuvant therapy after neoadjuvant therapy for locally advanced esophageal cancer, although subsets of patients might. Therefore, we sought to identify profiles of patients predicted to receive the most survival benefit or greatest detriment from adding adjuvant therapy. BACKGROUND Although neoadjuvant therapy has become the treatment of choice for locally advanced esophageal cancer, the value of adding adjuvant therapy is unknown. METHODS From 1970 to 2014, 22,123 patients were treated for esophageal cancer at 33 centers on 6 continents (Worldwide Esophageal Cancer Collaboration), of whom 7731 with adenocarcinoma or squamous cell carcinoma received neoadjuvant therapy; 1348 received additional adjuvant therapy. Random forests for survival and virtual-twin analyses were performed for all-cause mortality. RESULTS Patients received a small survival benefit from adjuvant therapy (3.2±10 months over the subsequent 10 years for adenocarcinoma, 1.8±11 for squamous cell carcinoma). Consistent benefit occurred in ypT3-4 patients without nodal involvement and those with ypN2-3 disease. The small subset of patients receiving most benefit had high nodal burden, ypT4, and positive margins. Patients with ypT1-2N0 cancers had either no benefit or a detriment in survival. CONCLUSIONS Adjuvant therapy after neoadjuvant therapy has value primarily for patients with more advanced esophageal cancer. Because the benefit is often small, patients considering adjuvant therapy should be counseled on benefits versus morbidity. In addition, given that the overall benefit was meaningful in a small number of patients, emerging modalities such as immunotherapy may hold more promise in the adjuvant setting.
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Affiliation(s)
- Siva Raja
- Heart, Vascular, and Thoracic Institute, Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic, Cleveland, Ohio
| | - Thomas W. Rice
- Heart, Vascular, and Thoracic Institute, Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic, Cleveland, Ohio
| | - Min Lu
- Department of Public Health Sciences, Division of Biostatistics, University of Miami, Miami, Florida
| | - Marie E. Semple
- Lerner Research Institute, Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio
| | - Eugene H. Blackstone
- Heart, Vascular, and Thoracic Institute, Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic, Cleveland, Ohio
- Lerner Research Institute, Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio
| | - Sudish C. Murthy
- Heart, Vascular, and Thoracic Institute, Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic, Cleveland, Ohio
| | - Usman Ahmad
- Heart, Vascular, and Thoracic Institute, Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic, Cleveland, Ohio
| | - Michael McNamara
- Taussig Cancer Institute, Department of Hematology and Medical Oncology, Cleveland Clinic, Cleveland, Ohio
| | - Andrew J. Toth
- Lerner Research Institute, Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio
| | - Ishwaran Hemant
- Department of Public Health Sciences, Division of Biostatistics, University of Miami, Miami, Florida
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Authors, und die Mitarbeiter der Leitlinienkommission, Collaborators:. S3-Leitlinie Diagnostik und Therapie der Plattenepithelkarzinome und Adenokarzinome des Ösophagus. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2023; 61:e209-e307. [PMID: 37285869 DOI: 10.1055/a-1771-6953] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
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11
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Tamamura H, Hasatani K, Matsumoto S, Asahi S, Tatebe H, Sato Y, Matsusita K, Tameshige Y, Maeda Y, Sasaki M, Takamatsu S, Yamamoto K. Evaluation of Exposure Doses of Elective Nodal Irradiation in Chemoradiotherapy for Advanced Esophageal Cancer. Cancers (Basel) 2023; 15:cancers15030860. [PMID: 36765818 PMCID: PMC9913169 DOI: 10.3390/cancers15030860] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2022] [Revised: 01/22/2023] [Accepted: 01/27/2023] [Indexed: 01/31/2023] Open
Abstract
We evaluated elective nodal irradiation (ENI) doses during radical chemoradiotherapy (CRT) for esophageal cancer (EC). A total of 79 patients (65 men and 14 women) aged 52-80 years with T1-3, N0-3, and M0 (including M1ly) who underwent CRT for EC during November 2012-September 2019 were eligible for this retrospective analysis. Patients were divided into two groups: the high-dose group (HG), including 38 patients who received ≥40 Gy as ENI; and the low-dose group (LG), including 41 patients who received <40 Gy. The median doses were 40.0 and 36.0 Gy in HG and LG, respectively. During the follow-up (median: 36.7 months), no lymph node recurrence was observed in the ENI field in all patients. Lymph node recurrence near the ENI field was observed in six patients. No significant differences were observed between the two groups in median overall survival, progression-free survival, and local control. Grade 3-4 acute and late adverse events were observed in five patients of HG and six patients of LG, respectively. No ulceration or stricture was observed in the ENI field on endoscopy examined with 58 Gy irradiation. In conclusion, an ENI dose of 36 Gy could be considered to control the elective nodes of EC.
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Affiliation(s)
- Hiroyasu Tamamura
- Proton Therapy Center, Fukui Prefectural Hospital, 2-8-1 Yotsui, Fukui City 910-8526, Fukui Prefecture, Japan
- Correspondence: ; Tel.: +81-0776-57-2981; Fax: +81-0776-57-2987
| | - Kenkei Hasatani
- Department of Gastroenterology, Fukui Prefectural Hospital, 2-8-1 Yotsui, Fukui City 910-8526, Fukui Prefecture, Japan
| | - Sae Matsumoto
- Proton Therapy Center, Fukui Prefectural Hospital, 2-8-1 Yotsui, Fukui City 910-8526, Fukui Prefecture, Japan
| | - Satoko Asahi
- Proton Therapy Center, Fukui Prefectural Hospital, 2-8-1 Yotsui, Fukui City 910-8526, Fukui Prefecture, Japan
| | - Hitoshi Tatebe
- Proton Therapy Center, Fukui Prefectural Hospital, 2-8-1 Yotsui, Fukui City 910-8526, Fukui Prefecture, Japan
| | - Yoshitaka Sato
- Proton Therapy Center, Fukui Prefectural Hospital, 2-8-1 Yotsui, Fukui City 910-8526, Fukui Prefecture, Japan
| | - Keiichiro Matsusita
- Proton Therapy Center, Fukui Prefectural Hospital, 2-8-1 Yotsui, Fukui City 910-8526, Fukui Prefecture, Japan
| | - Yuji Tameshige
- Proton Therapy Center, Fukui Prefectural Hospital, 2-8-1 Yotsui, Fukui City 910-8526, Fukui Prefecture, Japan
| | - Yoshikazu Maeda
- Proton Therapy Center, Fukui Prefectural Hospital, 2-8-1 Yotsui, Fukui City 910-8526, Fukui Prefecture, Japan
| | - Makoto Sasaki
- Proton Therapy Center, Fukui Prefectural Hospital, 2-8-1 Yotsui, Fukui City 910-8526, Fukui Prefecture, Japan
| | - Shigeyuki Takamatsu
- Department of Radiotherapy, Kanazawa University Hospital, Kanazawa 920-8641, Ishikawa, Japan
| | - Kazutaka Yamamoto
- Proton Therapy Center, Fukui Prefectural Hospital, 2-8-1 Yotsui, Fukui City 910-8526, Fukui Prefecture, Japan
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12
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Han J, Hayashi S, Takahashi RU, Hirohata R, Kurokawa T, Tashiro M, Yamamoto Y, Okada M, Tahara H. Leukocyte Telomeric G-Tail Length Shortening Is Associated with Esophageal Cancer Recurrence. J Clin Med 2022; 11:jcm11247385. [PMID: 36556001 PMCID: PMC9784295 DOI: 10.3390/jcm11247385] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 12/08/2022] [Accepted: 12/09/2022] [Indexed: 12/14/2022] Open
Abstract
Despite significant advances in therapeutics for esophageal cancer (ESC) in the past decade, it remains the sixth most fatal malignancy, with a poor 5-year survival rate (approximately 10%). There is an urgent need to improve the timely diagnosis to aid the prediction of the therapeutic response and prognosis of patients with ESC. The telomeric G-tail plays an important role in the chromosome protection. However, aging and age-related diseases lead to its shortening. Therefore, the G-tail length has been proposed as a novel potential biomarker. In the present study, to examine the possibility of G-tail shortening in patients with ESC, we measured the leukocyte telomere length (LTL) and the G-tail length using a hybridization protection assay in 147 patients with ESC and 170 age-matched healthy controls. We found that the G-tail length in patients with ESC was shorter than that in the healthy controls (p = 0.02), while the LTL shortening was not correlated with the ESC incidence and recurrence. Our results suggest that the G-tail length reflects the physiological status of patients with ESC and is a promising biomarker for the diagnosis and prognosis of ESC.
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Affiliation(s)
- Jiayan Han
- Department of Cellular and Molecular Biology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima 734-8553, Japan
| | - Soichiro Hayashi
- Department of Cellular and Molecular Biology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima 734-8553, Japan
| | - Ryou-u Takahashi
- Department of Cellular and Molecular Biology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima 734-8553, Japan
| | - Ryosuke Hirohata
- Department of Surgical Oncology, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima 734-0037, Japan
| | - Tomoaki Kurokawa
- Department of Surgical Oncology, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima 734-0037, Japan
| | - Mizuki Tashiro
- Department of Cellular and Molecular Biology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima 734-8553, Japan
| | - Yuki Yamamoto
- Department of Cellular and Molecular Biology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima 734-8553, Japan
| | - Morihito Okada
- Department of Surgical Oncology, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima 734-0037, Japan
| | - Hidetoshi Tahara
- Department of Cellular and Molecular Biology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima 734-8553, Japan
- Correspondence: ; Tel.: +81-08-2257-5290 (ext. 5290)
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13
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Du J, Xu G, Yang Z, Zheng B, Chen C. Pericancerous lymph node imaging with indocyanine green-guided near-infrared fluorescence in radical esophagectomy: Protocol for a single-center, prospective, randomized controlled clinical trial. Thorac Cancer 2022; 13:2283-2287. [PMID: 35770339 PMCID: PMC9346187 DOI: 10.1111/1759-7714.14548] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2022] [Revised: 06/05/2022] [Accepted: 06/07/2022] [Indexed: 11/27/2022] Open
Abstract
INTRODUCTION The incidence and mortality rates of esophageal carcinoma are higher than those of most malignancies in humans. Radical esophagectomy is the preferred treatment for early-stage esophageal cancer. However, the extent of lymphadenectomy during radical esophagectomy remains controversial. Indocyanine green (ICG) is the most commonly used imaging agent for the diagnosis of tumors and metastatic lymph nodes in clinical settings. Thus, the main aim of this study was to evaluate pericancerous lymph nodes imaging in video-assisted thoracoscopic surgery radical esophagectomy using a near-infrared (NIR) ICG imaging system and to improve the detection rate of sentinel lymph nodes (SLNs) and overall survival of patients with esophageal cancer. METHODS This was a single-center, prospective, randomized controlled clinical trial (allocation rate = 1:1). Forty treatment-naive esophageal cancer patients were recruited and divided into two groups: the ICG and control groups. The inclusion criteria were age, absence of preoperative neoadjuvant therapy, elective surgery, and signed informed consent. Data of participants at four different time points (preoperation, intraoperation, postoperative 1 week and 3 months) were collected and recorded. The main endpoint of this study was to explore the accuracy and false-negative rate of lymphadenectomy using NIR-ICG fluorescence imaging and to identify the location of esophageal cancer SLN combined with postoperative pathological reports. DISCUSSION This trial will provide more evidence on the extent of lymph node dissection for esophageal cancer and contribute to the development of treatment guidelines for esophageal cancer. TRIAL REGISTRATION NUMBER NCT04615806.
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Affiliation(s)
- Jianting Du
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China.,Key Laboratory of Cardio-Thoracic Surgery(Fujian Medical University), Fujian Province University, Fuzhou, Fujian, China
| | - Guobing Xu
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China.,Key Laboratory of Cardio-Thoracic Surgery(Fujian Medical University), Fujian Province University, Fuzhou, Fujian, China
| | - Zhang Yang
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China.,Key Laboratory of Cardio-Thoracic Surgery(Fujian Medical University), Fujian Province University, Fuzhou, Fujian, China
| | - Bin Zheng
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China.,Key Laboratory of Cardio-Thoracic Surgery(Fujian Medical University), Fujian Province University, Fuzhou, Fujian, China
| | - Chun Chen
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China.,Key Laboratory of Cardio-Thoracic Surgery(Fujian Medical University), Fujian Province University, Fuzhou, Fujian, China
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14
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Wang Y, Xiao P, Yang N, Wang X, Ma K, Wu L, Zhang W, Zhuang X, Xie T, Fang Q, Lan M, Wang Q, Peng L. Unresected small lymph node assessment predicts prognosis for patients with pT3N0M0 thoracic esophageal squamous cell carcinoma. World J Surg Oncol 2021; 19:303. [PMID: 34657600 PMCID: PMC8522218 DOI: 10.1186/s12957-021-02412-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Accepted: 09/30/2021] [Indexed: 12/19/2022] Open
Abstract
Background The role of unresected small lymph nodes (LNs) which may contain metastases for thoracic esophageal squamous cell carcinoma (TESCC) has not been addressed. The aim of the study was to investigate the role of unresected small LNs assessment using computed tomography (CT) in prognostic estimates of pT3N0M0 TESCC patients. Methods Between January 2009 and December 2017, 294 patients who underwent esophagectomy with R0 resection at Sichuan Cancer Hospital were retrospectively examined, and the last follow-up time was July 2018. Patients were classified into CT-suspect and CT-negative groups according to the shortest diameter and the shape (axial ratio) of the unresected small LNs on preoperative CT. The Kaplan–Meier method was used to compare survival differences in prognostic factors. Univariate and multivariate analyses were performed to identify prognostic factors for survival and recurrence. Results Eighty-four patients (28.6%) were classified as CT-suspect group according to the diagnostic criteria; survival analysis suggested that CT-suspect group of patients had a relatively poorer prognosis (P<0.05). Cox regression analysis indicated that unresected small LNs status, tumor grade, and postoperative adjuvant therapy were independent prognostic factors for patients with pT3N0M0 TESCC (P<0.05). Further analysis shown the rates of total recurrence (TR) and locoregional recurrence (LR) in the CT-suspect group were significantly higher than that in the CT-negative group (TR, P<0.001; LR, P<0.001). Among the LRs, the rate of supraclavicular lymph node recurrence in the CT-suspect group was significantly higher than that in the CT-negative group (P<0.001). Conclusions Unresected small lymph node assessment is critically important and predict prognosis for pT3N0M0 TESCC patients. Supplementary Information The online version contains supplementary material available at 10.1186/s12957-021-02412-1.
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Affiliation(s)
- Yi Wang
- Department of Radiation Oncology, Sichuan Cancer Hospital and Institution, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Radiation Oncology Key Laboratory of Sichuan Province, No.55,Section 4,South Renmin Road, Chengdu, 610042, China.,Department of Medical Oncology, Sichuan Cancer Hospital and Institution, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Ping Xiao
- Department of Thoracic Surgery, Sichuan Cancer Hospital and Institution, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Ningjing Yang
- Department of Radiology, Sichuan Cancer Hospital and Institution, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Xiang Wang
- Department of Thoracic Surgery, Sichuan Cancer Hospital and Institution, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Ke Ma
- Department of Thoracic Surgery, Sichuan Cancer Hospital and Institution, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Lei Wu
- Department of Radiation Oncology, Sichuan Cancer Hospital and Institution, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Radiation Oncology Key Laboratory of Sichuan Province, No.55,Section 4,South Renmin Road, Chengdu, 610042, China.,Department of Medical Oncology, Sichuan Cancer Hospital and Institution, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Wei Zhang
- Department of PET/CT center, Sichuan Cancer Hospital and Institution, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Xiang Zhuang
- Department of Thoracic Surgery, Sichuan Cancer Hospital and Institution, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Tianpeng Xie
- Department of Thoracic Surgery, Sichuan Cancer Hospital and Institution, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Qiang Fang
- Department of Thoracic Surgery, Sichuan Cancer Hospital and Institution, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Mei Lan
- Department of Radiation Oncology, Sichuan Cancer Hospital and Institution, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Radiation Oncology Key Laboratory of Sichuan Province, No.55,Section 4,South Renmin Road, Chengdu, 610042, China.,Department of Medical Oncology, Sichuan Cancer Hospital and Institution, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Qifeng Wang
- Department of Radiation Oncology, Sichuan Cancer Hospital and Institution, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Radiation Oncology Key Laboratory of Sichuan Province, No.55,Section 4,South Renmin Road, Chengdu, 610042, China. .,Department of Medical Oncology, Sichuan Cancer Hospital and Institution, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
| | - Lin Peng
- Department of Thoracic Surgery, Sichuan Cancer Hospital and Institution, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
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15
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Benech N, O'Brien JM, Barret M, Jacques J, Rahmi G, Perrod G, Hervieu V, Jaouen A, Charissoux A, Guillaud O, Legros R, Walter T, Saurin JC, Rivory J, Prat F, Lépilliez V, Ponchon T, Pioche M. Endoscopic resection of Barrett's adenocarcinoma: Intramucosal and low-risk tumours are not associated with lymph node metastases. United European Gastroenterol J 2021; 9:362-369. [PMID: 32903167 PMCID: PMC8259244 DOI: 10.1177/2050640620958903] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Accepted: 08/18/2020] [Indexed: 12/20/2022] Open
Abstract
Background Superficial oesophageal adenocarcinoma can be resected endoscopically, but data to define a curative endoscopic resection are scarce. Objective Our study aimed to assess the risk of lymph node metastasis depending on the depth of invasion and histological features of oesophageal adenocarcinoma. Methods We retrospectively included all patients undergoing an endoscopic resection for T1 oesophageal adenocarcinoma among seven expert centres in France in 2004–2016. Mural invasion was defined as either intramucosal or submucosal tumours; the latter were further divided into superficial submucosal (<1000 mm) and deep submucosal (>1000 mm). Absence or presence of lymphovascular invasion and/or poorly differentiated cancer (G3) defined a low‐risk or a high‐risk tumour, respectively. For submucosal tumours, invasion depth and histological features were systematically confirmed after a second dedicated histological assessment (new 2‐mm thick slices) performed by a second pathologist. Occurrence of lymph node metastasis was recorded during the follow‐up from histological or PET CT reports when an invasive procedure was not possible. Results In total, 188 superficial oesophageal adenocarcinomas were included with a median follow‐up of 34 months. No lymph node metastases occurred for intramucosal oesophageal adenocarcinomas (n = 135) even with high‐risk histological features. Among submucosal oesophageal adenocarcinomas, only tumours with lymphovascular invasion or poorly differentiated cancer or with a depth of invasion >1000 μm developed lymph node metastasis tumours (n = 10/53%; 18.9%; hazard ratio 12.04). No metastatic evolution occurred under a 1000‐mm threshold for all low‐risk tumours (0/25), nor under 1200 mm (0/1) and three over this threshold (3/13%, 23.1%). Conclusion Intramucosal and low‐risk tumours with shallow submucosal invasion up to 1200 mm were not associated with lymph node metastasis during follow‐up. In case of high‐risk features and/or deep submucosal invasion, endoscopic resections are not sufficient to eliminate the risk of lymph node metastasis, and surgical oesophagectomy should be carried out. These results must be confirmed by larger prospective series.
Superficial oesophageal adenocarcinoma (OAC) can be resected endoscopically. Data to define a curative endoscopic resection with a low lymph node metastasis (LNM) risk are scarce especially for tumours invading the submucosa. Curative endoscopic resections have been reported in selected OAC invading the first 500 mm of the submucosa, but surgical series showed an LNM risk ranging from 0% to 50%, making endoscopic resection a questionable curative treatment. High‐risk histological features were not associated with LNM in intramucosal tumours. LNM occurred only for tumours invading the submucosa with a depth ≥1200 mm or with high‐risk histological features regardless of the depth of invasion. Endoscopic resection may be a valid and curative therapeutic option for all intramucosal tumours and for submucosal oesophageal adenocarcinoma with an invasion depth ≤1000 mm and low‐risk histological features.
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Affiliation(s)
- Nicolas Benech
- Service d'Hépato-Gastroentérologie, Hôpital Edouard Herriot, Hospices civils de Lyon, Lyon, France.,Université Claude Bernard Lyon 1, Lyon, France
| | - Jean Marc O'Brien
- Université Claude Bernard Lyon 1, Lyon, France.,Service d'Hépato-Gastroentérologie, Hôpital de La Croix-Rousse, Hospices civils de Lyon, Lyon, France
| | | | - Jéremie Jacques
- Service d'Hepato-Gastroenterologie, Dupuytren University Hospital, Limoges, France
| | - Gabriel Rahmi
- Service d'Hepato-Gastroenterologie, Hôpital Europeen Georges Pompidou, Paris, France
| | - Guillaume Perrod
- Service d'Hepato-Gastroenterologie, Hôpital Europeen Georges Pompidou, Paris, France
| | - Valérie Hervieu
- Service d'Anatomo-Pathologie, Hôpital Edouard Herriot, Hospices civils de Lyon, Lyon, France
| | - Alexandre Jaouen
- Service d'Anatomo-Pathologie, Hôpital Edouard Herriot, Hospices civils de Lyon, Lyon, France
| | - Aurélie Charissoux
- Service d'Anatomo-Pathologie, Dupuytren University Hospital, Limoges, France
| | - Olivier Guillaud
- Service d'Hepato-Gastroenterologie, Clinique de la Sauvegarde, Lyon, France
| | - Romain Legros
- Service d'Hepato-Gastroenterologie, Dupuytren University Hospital, Limoges, France
| | - Thomas Walter
- Service d'Hépato-Gastroentérologie, Hôpital Edouard Herriot, Hospices civils de Lyon, Lyon, France
| | - Jean-Christophe Saurin
- Service d'Hépato-Gastroentérologie, Hôpital Edouard Herriot, Hospices civils de Lyon, Lyon, France
| | - Jérôme Rivory
- Service d'Hépato-Gastroentérologie, Hôpital Edouard Herriot, Hospices civils de Lyon, Lyon, France.,Université Claude Bernard Lyon 1, Lyon, France
| | - Fréderic Prat
- Service d'Hepato-Gastroentérologie, Hôpital Cochin, Paris, France
| | - Vincent Lépilliez
- Service d'Hepato-Gastroentérologie, Mermoz Private Hospital, Lyon, France
| | - Thierry Ponchon
- Service d'Hépato-Gastroentérologie, Hôpital Edouard Herriot, Hospices civils de Lyon, Lyon, France.,Université Claude Bernard Lyon 1, Lyon, France.,INSERM U1032, Lab Tau, Lyon, France
| | - Mathieu Pioche
- Service d'Hépato-Gastroentérologie, Hôpital Edouard Herriot, Hospices civils de Lyon, Lyon, France.,Université Claude Bernard Lyon 1, Lyon, France.,INSERM U1032, Lab Tau, Lyon, France
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16
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Chen P, Zheng Y, He H, Wang PY, Wang F, Liu SY. The role of endoscopic tumor length in resected esophageal squamous cell carcinoma: a retrospective study. J Thorac Dis 2021; 13:353-361. [PMID: 33569215 PMCID: PMC7867824 DOI: 10.21037/jtd-21-108] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Background In esophageal squamous cell carcinoma (ESCC), tumor status is assessed on the basis of latitudinal invasion. Endoscopic tumor length (ETL) may represent the longitudinal scope of the primary tumor, and whether it affects tumor stage or prognosis is not entirely clear. In this study, we evaluated the role of ETL in patients with resected ESCC. Methods The relationships of ETL with pathological parameters (pT status and pN status) and overall survival (OS) were analyzed using data from patients with resected ESCC who were treated at Fujian Cancer Hospital between January 1997 and December 2013. Odds ratios (ORs) and hazard ratios (HRs) were fitted with locally weighted scatterplot smoothing, and the structural breakpoints for ETL were determined using the Chow test. Results A total of 721 patients with resected ESCC were enrolled. As the ETL increased in these patients, a rise in the risk of advanced pT status, nodal metastasis, and mortality was observed. Cutpoint analysis showed a breakpoint of 7.0 cm. A negative impact of ETL ≥7.0 cm was also found (adjusted HR, 1.335; 95% CI, 1.004–1.774). Seven independent prognostic factors, including sex, age, number of nodes dissected, T stage, N stage, tumor location, and ETL, were identified and entered into the nomogram. The calibration curves for 1-, 3-, and 5-year OS showed optimal agreement between nomogram prediction and actual observation (c-index: 0.688). Conclusions Longer tumor length, with ETL ≥7.0 cm as the breakpoint, is a negative prognostic factor in patients with ESCC.
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Affiliation(s)
- Peng Chen
- Department of Thoracic Surgery, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, China
| | - Yuzhen Zheng
- Department of Thoracic Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Hao He
- Department of Thoracic Surgery, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, China
| | - Pei Yuan Wang
- Department of Thoracic Surgery, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, China
| | - Feng Wang
- Department of Thoracic Surgery, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, China
| | - Shuo Yan Liu
- Department of Thoracic Surgery, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, China
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17
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Kumarasinghe MP, Armstrong M, Foo J, Raftopoulos SC. The modern management of Barrett's oesophagus and related neoplasia: role of pathology. Histopathology 2020; 78:18-38. [PMID: 33382493 DOI: 10.1111/his.14285] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2020] [Revised: 10/14/2020] [Accepted: 10/21/2020] [Indexed: 12/13/2022]
Abstract
Modern management of Barrett's oesophagus and related neoplasia essentially focuses upon surveillance to detect early low-risk neoplastic lesions and offering organ-preserving advanced endoscopic therapies, while traditional surgical treatments of oesophagectomy and lymph node clearance with or without chemoradiation are preserved only for high-risk and advanced carcinomas. With this evolution towards figless invasive therapy, the choice of therapy hinges upon the pathological assessment for risk stratifying patients into those with low risk for nodal metastasis who can continue with less invasive endoscopic therapies and others with high risk for nodal metastasis for which surgery or other forms of treatment are indicated. Detection and confirmation of neoplasia in the first instance depends upon endoscopic and pathological assessment. Endoscopic examination and biopsy sampling should be performed according to the recommended protocols, and endoscopic biopsy interpretation should be performed applying standard criteria using appropriate ancillary studies by histopathologists experienced in the pathology of Barrett's disease. Endoscopic resections (ERs) are both diagnostic and curative and should be performed by clinicians who are skilled with advanced endoscopic techniques. Proper preparation and handling of ERs are essential to assess histological parameters that dictate the curative nature of the procedure. Those parameters are adequacy of resection and risk of lymph node metastasis. The risk of lymph node metastasis is determined by depth invasion and presence of poor differentiation and lymphovascular invasion. Those adenocarcinomas with invasion up to muscularis mucosae (pT1a) and those with superficial submucosal invasion (pT1b) up to 500 µ with no poor differentiation and lymphovascular invasion and negative margins may be considered cured by endoscopic resections.
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Affiliation(s)
- M Priyanthi Kumarasinghe
- PathWest and Clinipath Laboratories and Sir Charles Gairdner Hospital, QEII Medical Centre, Perth, 6009, WA, Australia
| | - Michael Armstrong
- PathWest and Clinipath Laboratories and Sir Charles Gairdner Hospital, QEII Medical Centre, Perth, 6009, WA, Australia
| | - Jonathan Foo
- PathWest and Clinipath Laboratories and Sir Charles Gairdner Hospital, QEII Medical Centre, Perth, 6009, WA, Australia
| | - Spiro C Raftopoulos
- PathWest and Clinipath Laboratories and Sir Charles Gairdner Hospital, QEII Medical Centre, Perth, 6009, WA, Australia
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18
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Nusrath S, Saxena AR, Raju KVVN, Patnaik S, Subramanyeshwar Rao T, Bollineni N. The Value of Lymphadenectomy Post-Neoadjuvant Therapy in Carcinoma Esophagus: a Review. Indian J Surg Oncol 2020; 11:538-548. [PMID: 33013140 DOI: 10.1007/s13193-020-01156-w] [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: 02/19/2020] [Accepted: 06/30/2020] [Indexed: 10/23/2022] Open
Abstract
Lymph nodal metastasis is one of the most important prognostic factors determining survival in patients with carcinoma esophagus. Radical esophagectomy, with the resection of surrounding lymph nodes, is considered the prime treatment of carcinoma esophagus. An extensive lymphadenectomy improves the accuracy of staging and betters locoregional control, but its effect on survival is still not apparent and carries the disadvantage of increased morbidity. The extent of lymphadenectomy during esophagectomy also remains debatable, with many studies revealing contradictory results, especially in the era of neoadjuvant therapy. The pattern of distribution and the number of nodal metastasis are modified by neoadjuvant therapy. The paper reviews the existing evidence to determine whether increased lymph node yield improves oncological outcomes in patients undergoing esophagectomy with particular attention to those patients receiving neoadjuvant therapy.
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Affiliation(s)
- Syed Nusrath
- Department of Surgical Oncology, Basavatarakam Indo American Cancer Hospital and Research Institute, Hyderabad, India
| | - Ajesh Raj Saxena
- Department of Surgical Oncology, Basavatarakam Indo American Cancer Hospital and Research Institute, Hyderabad, India
| | - K V V N Raju
- Department of Surgical Oncology, Basavatarakam Indo American Cancer Hospital and Research Institute, Hyderabad, India
| | - Sujith Patnaik
- Department of Surgical Oncology, Basavatarakam Indo American Cancer Hospital and Research Institute, Hyderabad, India
| | - T Subramanyeshwar Rao
- Department of Surgical Oncology, Basavatarakam Indo American Cancer Hospital and Research Institute, Hyderabad, India
| | - Naren Bollineni
- Department of Surgical Oncology, Basavatarakam Indo American Cancer Hospital and Research Institute, Hyderabad, India
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19
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Kumarasinghe MP, Bourke MJ, Brown I, Draganov PV, McLeod D, Streutker C, Raftopoulos S, Ushiku T, Lauwers GY. Pathological assessment of endoscopic resections of the gastrointestinal tract: a comprehensive clinicopathologic review. Mod Pathol 2020; 33:986-1006. [PMID: 31907377 DOI: 10.1038/s41379-019-0443-1] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2019] [Revised: 11/27/2019] [Accepted: 12/10/2019] [Indexed: 12/13/2022]
Abstract
Endoscopic resection (ER) allows optimal staging with potential cure of early-stage luminal malignancies while maintaining organ preservation. ER and surgery are non-competing but complementary therapeutic options. In addition, histological examination of ER specimens can either confirm or refine the pre-procedure diagnosis. ER is used for the treatment of Barrett's related early carcinomas and dysplasias, early-esophageal squamous cell carcinomas and dysplasias, early gastric carcinomas and dysplasia, as well as low-risk submucosal invasive carcinomas (LR-SMIC) and, large laterally spreading adenomas of the colon. For invasive lesions, histological risk factors predict risk of lymph node metastasis and residual disease at the ER site. Important pathological risk factors predictive of lymph node metastasis are depth of tumor invasion, poor differentiation, and lymphovascular invasion. Complete resection with negative margins is critical to avoid local recurrences. For non-invasive lesions, complete resection is curative. Therefore, a systematic approach for handling and assessing ER specimens is recommended to evaluate all above key prognostic features appropriately. Correct handling starts with pinning the specimen before fixation, meticulous macroscopic assessment with orientation of appropriate margins, systematic sectioning, and microscopic assessment of the entire specimen. Microscopic examination should be thorough for accurate assessment of all pathological risk factors and margin assessment. Site-specific issues such as duplication of muscularis mucosa of the esophagus, challenges of assessing ampullectomy specimens and site-specific differences of staging of early carcinomas throughout the gastrointestinal tract (GI) tract should be given special consideration. Finally, a standard, comprehensive pathology report that allows optimal staging with potential cure of early-stage malignancies or better stratification and guidance for additional treatment should be provided.
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Affiliation(s)
- M Priyanthi Kumarasinghe
- Department of Anatomical Pathology, PathWest, QE II Medical Centre and School of Pathology and Laboratory Medicine, University of Western Australia, Hospital Avenue, Nedlands Perth, WA, 6009, Australia.
| | - Michael J Bourke
- Department of Medicine, University of Sydney, Westmead Hospital, Westmead, NSW, 2145, Australia
| | - Ian Brown
- Envoi Pathology,Unit 5, 38 Bishop Street, Kelvin Grove, QLD, 4059, Australia.,Royal Brisbane and Women's Hospital, Herston, QLD, 4029, Australia
| | - Peter V Draganov
- Department of Medicine, University of Florida, 1329 SW 16th Street, Room # 5251, Gainesville, FL, 32608, USA
| | | | - Catherine Streutker
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Director of Pathology, St Michael's Hospital, Toronto, ON, M5B 1W9, Canada
| | - Spiro Raftopoulos
- Sir Charles Gairdner Hospital, QE II Medical Centre, Hospital Avenue, Nedlands Perth, WA, 6009, Australia
| | - Tetsuo Ushiku
- Department of Pathology, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan
| | - Gregory Y Lauwers
- H. Lee Moffitt Cancer Center & Research Institute and Departments of Pathology & Cell Biology and Oncologic Sciences, University of South Florida, Tampa, FL, USA
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20
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Deng J, Chu X, Ren Z, Wang B. Relationship between T stage and survival in distantly metastatic esophageal cancer: A STROBE-compliant study. Medicine (Baltimore) 2020; 99:e20064. [PMID: 32384472 PMCID: PMC7220676 DOI: 10.1097/md.0000000000020064] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
To shed light on the interaction between the American Joint Committee on Cancer (AJCC) T stage and M stage in the determination of the overall survival (OS) and cancer-specific survival (CSS) of esophageal carcinoma patients. Moreover, to confirm our hypothesis that tumors that metastasize to distant sites in the early T stage may reflect a more biologically aggressive disease compared with those that metastasize in more advanced T stages.We performed a retrospective cohort study with patients who were pathologically diagnosed with esophageal cancer between 2004 and 2014 in the surveillance epidemiology and end results (SEER) database. The primary study variables were the T and M stage, as well as their interaction terms. We performed a survival analysis of the interaction terms using unadjusted Kaplan-Meier methods and adjusted Cox proportional hazards models. Furthermore, we performed an exploratory analysis with stratification by histological type, esophageal adenocarcinoma (EAC), and esophageal squamous cell carcinoma (ESCC).Data of 19,078 patients were retrieved from the SEER database. Unadjusted Kaplan-Meier curve indicated that patients with T2 and T3 stage had longer median OS and CSS (3 months and 4 months, respectively) than with T1 stage in distantly metastatic esophageal cancer (M1 stage). Multivariate analysis revealed a significant interaction between the T stage and M stage when determining the OS and CSS of esophageal cancer (P < .001). Using T1M0 as a reference, patients with T1M1 had significantly worse OS and CSS than those with T2M1 and T3M1 stage (P < .001). A similar pattern was also observed among patients with EAC and ESCC.Our analysis suggests that the T1 stage predicts worse survival compared with T2 and T3 stage in distantly metastatic esophageal cancer and might be a surrogate for biologically aggressive disease, indicating that those patients should receive more aggressive treatments. Our findings also encourage researchers to discover new genomic changes in this subset of tumors with the potential to uncover new prognostic markers or drug targets. Further researches on the association between T stage and survival in metastatic esophageal cancer are warranted to validate our findings.
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Schurink B, Mazza E, Ruurda JP, Roeling TAP, Bleys RLAW, van Hillegersberg R. Metastatic incidence of (PET)CT positive lung hilar and retroperitoneal lymph nodes in esophageal cancer patients. Surg Oncol 2020; 33:170-176. [PMID: 32561084 DOI: 10.1016/j.suronc.2020.02.012] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2019] [Revised: 01/23/2020] [Accepted: 02/14/2020] [Indexed: 01/07/2023]
Abstract
BACKGROUND Extra-regional lymph node metastases strongly determine treatment options in patients with esophageal cancer. Staging modalities such as (FDG-PET) CT scanning frequently show activity in retroperitoneal and lung hilar lymph nodes. This study evaluated the incidence of histologically confirmed metastases, treatment approach and recurrence patterns in patients with (FDG-PET) CT positivity in these regions. METHODS All patients with (FDG-PET-) CT positive hilar and/or retroperitoneal lymph nodes at primary staging or restaging discussed at a multidisciplinary tumor board meeting for staging of esophageal cancer between January 2012-December 2017 were included. Biopsies and follow-up were evaluated to determine the presence of metastases and progression rates. RESULTS From 2012 to 2017, 65 of 857 patients (7.6%) were selected with positive retroperitoneal and/or hilar lymph nodes. A total of 47/65 (72.3%) patients had positive retroperitoneal lymph nodes, which contained metastases in 19 (29.2%). When no biopsy was performed and curative treatment was given (n = 14), 9 patients had progression or locoregional and distant recurrence. Positive hilar lymph nodes were identified in 21 (32.3%) patients; 4 were biopsied and none contained metastases. In these patients no recurrence of disease was seen during follow-up. CONCLUSIONS The majority of biopsied (PET)CT-positive retroperitoneal lymph nodes at staging contained metastases, while biopsied (PET)CT-positive hilar nodes did not. Histological evaluation of (PET)CT -positive retroperitoneal lymph nodes at staging imaging is recommended, while based on this small series, (PET)CT-positive hilar lymph nodes most likely represent reactive lymphadenopathy.
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Affiliation(s)
- B Schurink
- Department of Surgery, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, P.O. Box 85500, 3508 GA, Utrecht, the Netherlands; Department of Anatomy, University Medical Center Utrecht, Utrecht University, Universiteitsweg 100, P.O Box 85060, 3508 AB, Utrecht, the Netherlands.
| | - E Mazza
- Department of Surgery, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, P.O. Box 85500, 3508 GA, Utrecht, the Netherlands
| | - J P Ruurda
- Department of Surgery, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, P.O. Box 85500, 3508 GA, Utrecht, the Netherlands
| | - T A P Roeling
- Department of Anatomy, University Medical Center Utrecht, Utrecht University, Universiteitsweg 100, P.O Box 85060, 3508 AB, Utrecht, the Netherlands
| | - R L A W Bleys
- Department of Anatomy, University Medical Center Utrecht, Utrecht University, Universiteitsweg 100, P.O Box 85060, 3508 AB, Utrecht, the Netherlands
| | - R van Hillegersberg
- Department of Surgery, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, P.O. Box 85500, 3508 GA, Utrecht, the Netherlands.
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22
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Kumble LD, Silver E, Oh A, Abrams JA, Sonett JR, Hur C. Treatment of early stage (T1) esophageal adenocarcinoma: Personalizing the best therapy choice. World J Meta-Anal 2019; 7:406-417. [DOI: 10.13105/wjma.v7.i9.406] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2019] [Revised: 10/03/2019] [Accepted: 10/19/2019] [Indexed: 02/06/2023] Open
Abstract
Esophagectomy is considered the primary form of management for esophageal adenocarcinoma (EAC); however, the surgery is associated with high rates of morbidity and mortality. For patients with early-stage EAC, endoscopic resection (ER) presents a potential curative treatment option that is less invasive and carries fewer risks procedure related risks, but it is associated with higher rates of cancer recurrence following the procedure. For some patients, age and comorbidities may prevent them from having esophagectomy as a treatment option, while other patients may be operative candidates but do not wish to undergo esophagectomy for a variety of reasons related to their values and preferences. Furthermore, while anxiety of cancer recurrence following ER may significantly diminish a patient’s quality of life (QOL), so might the morbidity surrounding esophagectomy. In addition to considering health status, patient preferences, and impacts on QOL, physicians and patients must also consider what treatments would be both beneficial and available to the patient, considering esophagectomy methods-minimally invasive vs open-or the use of chemoradiotherapy in addition to ER. Our article reviews and summarizes available treatment options for patients with early EAC and their potential effects on the health and wellbeing of patients based on the current data. We conclude with a request for more research of available options for early EAC patients, the conditions that determine when each option should be employed, and their effects not only on patient health but also QOL.
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Affiliation(s)
| | - Elisabeth Silver
- General Medicine, Columbia University Medical Center, New York, NY 10032, United States
| | - Aaron Oh
- General Medicine, Columbia University Medical Center, New York, NY 10032, United States
| | - Julian A Abrams
- Department of Medicine, Columbia University Medical Center, New York, NY 10032, United States
| | - Joshua R Sonett
- Department of Medicine, Columbia University Medical Center, New York, NY 10032, United States
| | - Chin Hur
- Department of Medicine, Columbia University Medical Center, New York, NY 10032, United States
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Abstract
Traditionally, early esophageal cancer (i.e., cancer limited to the mucosa or superficial submucosa) was managed surgically; the gastroenterologist's role was primarily to diagnose the tumor. Over the last decade, advances in endoscopic imaging, ablation, and resection techniques have resulted in a paradigm shift-diagnosis, staging, treatment, and surveillance are within the endoscopist's domain. Yet, there are few reviews that provide a focused, evidence-based approach to early esophageal cancer, and highlight areas of controversy for practicing gastroenterologists. In this manuscript, we will discuss the following: (1) utility of novel endoscopic technologies to identify high-grade dysplasia and early esophageal cancer, (2) role of endoscopic resection and imaging to stage early esophageal cancer, (3) endoscopic therapies for early esophageal cancer, and (4) indications for surgical and multidisciplinary management.
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24
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Tian D, Huang H, Yang YS, Jiang KY, He X, Guo XG, Chen LQ. Depth of Invasion into the Circular and Longitudinal Muscle Layers in T2 Esophageal Squamous Cell Carcinoma Does Not Affect Prognosis or Lymph Node Metastasis: A Multicenter Retrospective Study. World J Surg 2019; 44:171-178. [PMID: 31552458 DOI: 10.1007/s00268-019-05194-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Although a greater depth of tumor invasion is correlated with a poorer prognosis in esophageal squamous cell carcinoma (ESCC), it remains controversial whether T2 ESCC should be subclassified by circular and longitudinal muscle invasion. We conducted a multicenter retrospective study to evaluate the relationship between the depth of invasion and long-term outcome and to identify the clinical significance of subclassifying T2 ESCC. METHODS Patients with T2 ESCC who underwent esophagectomy at two different institutes between January 2009 and December 2017 were analyzed retrospectively. ESCC with circular and longitudinal muscle invasion was defined as T2 circular and T2 longitudinal ESCC, respectively. Survival outcomes and risk factors for lymph node metastasis (LNM) were evaluated by univariate and multivariate analyses. In addition, data from stage T1b ESCC cases during the same period were retrieved for use as a comparison cohort to evaluate the prognostic significance of the T2 substage. RESULTS A total of 536 T2 ESCC patients were eligible, and 192 (36%) patients developed LNM. No significant difference was found in general characteristics between the T2 circular and T2 longitudinal ESCC groups (n = 219 and n = 317, P > 0.05), except for tumor location (P = 0.02). The T2 substage was not significantly correlated with survival on univariate or multivariate analysis (P = 0.30 and P = 0.34, respectively). Multivariate analysis also indicated that the T2 substage was not an independent risk factor for LNM (P = 0.15). When patients with stage T1b ESCC were considered, their survival time was significantly different from that of patients with T2 circular and T2 longitudinal disease (P = 0.01). CONCLUSIONS The depth of tumor invasion into the circular and longitudinal muscle layers in T2 ESCC does not affect the prognosis or risk of LNM.
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Affiliation(s)
- Dong Tian
- Department of Thoracic Surgery, West China Hospital, Sichuan University, 37 Guo Xue Xiang, Chengdu, 610041, China
- Department of Thoracic Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, China
| | - Heng Huang
- College of Clinical Medicine, North Sichuan Medical College, Nanchong, 637000, China
| | - Yu-Shang Yang
- Department of Thoracic Surgery, West China Hospital, Sichuan University, 37 Guo Xue Xiang, Chengdu, 610041, China
| | - Kai-Yuan Jiang
- College of Clinical Medicine, North Sichuan Medical College, Nanchong, 637000, China
| | - Xi He
- Institute of Imaging Medicine, North Sichuan Medical College, Nanchong, 637000, China
| | - Xiao-Guang Guo
- Department of Pathology, Nanchong Central Hospital, Nanchong, 637000, China
| | - Long-Qi Chen
- Department of Thoracic Surgery, West China Hospital, Sichuan University, 37 Guo Xue Xiang, Chengdu, 610041, China.
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25
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Endoscopic Submucosal Dissection for Esophageal Adenocarcinoma: A North American Perspective. J Gastrointest Surg 2019; 23:1087-1094. [PMID: 30847697 DOI: 10.1007/s11605-018-04093-w] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2017] [Accepted: 12/28/2018] [Indexed: 01/31/2023]
Abstract
BACKGROUND Data are limited regarding the application of endoscopic submucosal dissection (ESD) in Western countries or for esophageal adenocarcinoma in any part of the world. We sought to review our experience employing ESD in patients with early esophageal cancer at a high volume North American esophageal cancer treatment center. METHODS A prospectively maintained database of all patients with esophageal cancer treated at the McGill University Health Center was used to identify ESDs performed for adenocarcinoma between 2012 and 2016. Patient demographics, pre-resection tumor characteristics, endoscopic resection technical variables, pathologic results, and short- and long-term outcomes were recorded. RESULTS Of 650 patients in the database, 26 underwent 27 procedures. The majority (67%) had pre-treatment EUS. There were no post-ESD bleeding events requiring re-intervention. Perforation occurred in 2/27 (7%), one of which required operative repair. Complete RO resection was achieved in 18/27(67%). Salvage laparoscopic esophagectomy was performed in six patients. At a median follow-up of 18.5 (7-35) months, cancer recurrence occurred in only one patient who subsequently underwent successful repeat ESD. CONCLUSIONS Although technically challenging, ESD represents a safe and effective treatment of early esophageal adenocarcinoma and has the potential to become a more important tool in management of these early lesions in Western countries.
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26
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Kahn A, Kamboj AK, Muppa P, Sawas T, Lutzke LS, Buras MR, Golafshar MA, Katzka DA, Iyer PG, Smyrk TC, Wang KK, Leggett CL. Staging of T1 esophageal adenocarcinoma with volumetric laser endomicroscopy: a feasibility study. Endosc Int Open 2019; 7:E462-E470. [PMID: 30931378 PMCID: PMC6428686 DOI: 10.1055/a-0838-5326] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2018] [Accepted: 11/26/2018] [Indexed: 12/17/2022] Open
Abstract
Background and study aims Precise staging in T1 esophageal adenocarcinoma (EAC) is critical in determining candidacy for curative endoscopic resection. High-frequency endoscopic ultrasound (EUS) has demonstrated suboptimal accuracy in T1 EAC staging due to insufficient spatial resolution. Volumetric laser endomicroscopy (VLE) allows for high-resolution wide-field visualization of the esophageal microstructure. We aimed to investigate the role of VLE in staging T1 EAC. Patients and methods Patients undergoing endoscopic mucosal resection (EMR) were prospectively enrolled and only T1 EAC cases were included. EMR specimens were imaged using second-generation VLE immediately after resection. VLE images were analyzed for signal intensity by depth and signal attenuation (dB/mm) in both cross-sectional and en-face orientation. A decision tree model was constructed to combine measured VLE parameters and delineate diagnostic thresholds. Results Thirty EMR scans were obtained - 15 T1a specimens from 9 patients and 15 T1b specimens from 11 patients. T1b specimen VLE scans exhibited higher signal intensity ( P < 0.0001) and higher signal attenuation compared to T1a specimens ( P = 0.03). A combination of signal attenuation and signal intensity at 150 µm depth yielded optimal diagnostic thresholds and an area under the curve (AUC) of 0.77. VLE signal attenuation was significantly associated with grade of differentiation, irrespective of EAC stage. Conclusions VLE signal intensity and signal attenuation are quantitatively distinct in T1a and T1b EAC and associated with grade of differentiation. This is the first study examining the role of VLE for staging of T1 EAC and demonstrates promising diagnostic performance. With further in vivo validation, VLE may serve a role in staging superficial EAC.
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Affiliation(s)
- Allon Kahn
- Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, Arizona, United States
| | - Amrit K. Kamboj
- Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, United States
| | - Prasuna Muppa
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, United States
| | - Tarek Sawas
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, United States
| | - Lori S. Lutzke
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, United States
| | - Matthew R. Buras
- Division of Health Sciences Research, Mayo Clinic, Scottsdale, Arizona, United States
| | - Michael A. Golafshar
- Division of Health Sciences Research, Mayo Clinic, Scottsdale, Arizona, United States
| | - David A. Katzka
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, United States
| | - Prasad G. Iyer
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, United States
| | - Thomas C. Smyrk
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, United States
| | - Kenneth K. Wang
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, United States
| | - Cadman L. Leggett
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, United States,Corresponding author Cadman L. Leggett, M.D. Division of Gastroenterology and HepatologyMayo Clinic
200 1
st
Street SW, Rochester, MN 55905
+1-480-301-8673
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Yuen MTY, Tsang RK, Wong IYH, Chan DKK, Chan FSY, Law SYK. Long-term pharyngeal dysphagia after esophagectomy for esophageal cancer-an investigation using videofluoroscopic swallow studies. Dis Esophagus 2019; 32:5063837. [PMID: 30085000 DOI: 10.1093/dote/doy068] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Dysphagia is a common symptom of esophageal cancer (EC). Esophagectomy should relieve the presenting dysphagia as the mechanical obstruction caused by the tumor is removed. However, the new onset oropharyngeal dysphagia develops after esophagectomy and the deficit may persist increasing the risk of aspiration pneumonia and mortality as well as adversely affecting quality of life (QOL). This study investigates the persistent swallowing deficits in long-term postesophagectomy patients and explores the factors associated with dysphagia severity, penetration, and aspiration. A better understanding of the swallowing function can aid future management of the condition. A total of 29 patients who were more than six months postesophagectomy for EC, had no history of disease that would likely affect swallowing function or vocal cord palsy underwent detailed videofluoroscopic swallow studies and completed the European Organisation for Research and Treatment of Cancer QLQ-C30 and OES18 QOL questionnaires. Swallowing deficits were analyzed and rated using the videofluoroscopic dysphagia scale (VDS) and the penetration-aspiration scale (PAS). These variables were correlated with the clinical and QOL parameters to determine which factors would affect swallowing function. Our cohort consisted of 27 males and 2 females. The mean duration after esophagectomy when the swallowing study was performed was 3.2 years (range: 0.5-18.4 years). Swallowing deficits were mainly found in the pharyngeal phase of swallowing. The mean total VDS score was 36.1 (SD = 15.2, range: 11.0-69.5) out of a possible 100. The mean PAS score was 4.1 (SD = 2.5, range: 1-8) and 1.5 (SD = 0.9, range: 1-4) for thin and semisolids, respectively. Dysphagia was significantly more severe in males, those of more advanced age at esophagectomy and at swallowing assessment. Increasing pathological N stage significantly correlated with worse PAS score for thin fluid. Self-reports of more pain and less troubles with coughing were also associated with less penetration and aspiration. This study demonstrated that a mild to moderate pharyngeal dysphagia is present late after esophagectomy even in patients without VC palsy or anastomotic stricture. The long-term aspiration rate is comparable to the figures in the literature for those early after esophagectomy. It is suggested that damage to the intercostal nerves and the pulmonary vagus may affect oropharyngeal swallowing function in this population.
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Affiliation(s)
- M T Y Yuen
- Division of Otolaryngology.,Division of Esophageal and Upper Gastrointestinal Surgery, Department of Surgery, University of Hong Kong, Hong Kong
| | | | - I Y H Wong
- Division of Esophageal and Upper Gastrointestinal Surgery, Department of Surgery, University of Hong Kong, Hong Kong
| | - D K K Chan
- Division of Esophageal and Upper Gastrointestinal Surgery, Department of Surgery, University of Hong Kong, Hong Kong
| | - F S Y Chan
- Division of Esophageal and Upper Gastrointestinal Surgery, Department of Surgery, University of Hong Kong, Hong Kong
| | - S Y K Law
- Division of Esophageal and Upper Gastrointestinal Surgery, Department of Surgery, University of Hong Kong, Hong Kong
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Wang Y, Zhu L, Xia W, Wang F. Anatomy of lymphatic drainage of the esophagus and lymph node metastasis of thoracic esophageal cancer. Cancer Manag Res 2018; 10:6295-6303. [PMID: 30568491 PMCID: PMC6267772 DOI: 10.2147/cmar.s182436] [Citation(s) in RCA: 66] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
The lymphatic drainage of the inner layers (mucosa and submucosa) and the outer layers (muscularispropria and adventitia) of the thoracic esophagus is different. Longitudinal lymphatic vessels and long drainage territory in the submucosa and lamina propria should be the bases for bidirectional drainage and direct drainage to thoracic duct and extramural lymph nodes (LN). The submucosal vessels for direct extramural drainage are usually thick while lymphatic communication between the submucosa and intermuscular area is usually not clearly found, which does not facilitate transversal drainage to paraesophageal LN from submucosa. The right paratracheal lymphatic chain (PLC) is well developed while the left PLC is poorly developed. Direct drainage to the right recurrent laryngeal nerve LN and subcarinal LN from submucosa has been verified. Clinical data show that lymph node metastasis (LNM) is frequently present in the lower neck, upper mediastinum, and perigastric area, even for early-stage thoracic esophageal cancer (EC). The lymph node metastasis rate (LNMR) varies mainly according to the tumor location and depth of tumor invasion. However, there are some crucial LN for extramural relay which have a high LNMR, such as cervical paraesophageal LN, recurrent laryngeal nerve LN, subcarinal LN, LN along the left gastric artery, lesser curvature LN, and paracardial LN. Metastasis of thoracic paraesophageal LN seems to be a sign of more advanced EC. This review gives us a better understanding about the LNM and provides more information for treatments of thoracic EC.
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Affiliation(s)
- Yichun Wang
- Department of Radiation Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, P.R. China, ;
| | - Liyang Zhu
- Department of Radiation Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, P.R. China, ;
| | - Wanli Xia
- Department of Thoracic Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, P.R. China
| | - Fan Wang
- Department of Radiation Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, P.R. China, ;
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Graham D, Sever N, Magee C, Waddingham W, Banks M, Sweis R, Al-Yousuf H, Mitchison M, Alzoubaidi D, Rodriguez-Justo M, Lovat L, Novelli M, Jansen M, Haidry R. Risk of lymph node metastases in patients with T1b oesophageal adenocarcinoma: A retrospective single centre experience. World J Gastroenterol 2018; 24:4698-4707. [PMID: 30416317 PMCID: PMC6224466 DOI: 10.3748/wjg.v24.i41.4698] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2018] [Revised: 09/29/2018] [Accepted: 10/15/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To assess clinical outcomes for submucosal (T1b) oesophageal adenocarcinoma (OAC) patients managed with either surgery or endoscopic eradication therapy.
METHODS Patients found to have T1b OAC following endoscopic resection between January 2008 to February 2016 at University College London Hospital were retrospectively analysed. Patients were split into low-risk and high-risk groups according to established histopathological criteria and were then further categorised according to whether they underwent surgical resection or conservative management. Study outcomes include the presence of lymph-node metastases, disease-specific mortality and overall survival.
RESULTS A total of 60 patients were included; 22 patients were surgically managed (1 low-risk and 21 high-risk patients) whilst 38 patients were treated conservatively (12 low-risk and 26 high-risk). Overall, lymph node metastases (LNM) were detected in 10 patients (17%); six of these patients had undergone conservative management and LNM were detected at a median of 4 mo after endoscopic mucosal resection (EMR). All LNM occurred in patients with high-risk lesions and this represented 21% of the total high-risk lesions. Importantly, there was no statistically significant difference in tumor-related deaths between those treated surgically or conservatively (P = 0.636) and disease-specific survival time was also comparable between the two treatment strategies (P = 0.376).
CONCLUSION T1b tumours without histopathological high-risk markers of LNM can be treated endoscopically with good out-comes. In selected patients, endoscopic therapy may be appropriate for high-risk lesions.
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Affiliation(s)
- David Graham
- GI Services, University College London Hospital, London NW1 2BU, United Kingdom
- Division of Surgery and Science, University College London, London WC1E 6BT, United Kingdom
| | - Nejc Sever
- GI Services, University College London Hospital, London NW1 2BU, United Kingdom
- Gastroenterology Department, University Medical Center Ljubljana, Slovenia
| | - Cormac Magee
- GI Services, University College London Hospital, London NW1 2BU, United Kingdom
- Department of Metabolism and Experimental Therapeutics, University College London, London WC1E 6BT, United Kingdom
| | - William Waddingham
- GI Services, University College London Hospital, London NW1 2BU, United Kingdom
- Division of Surgery and Science, University College London, London WC1E 6BT, United Kingdom
| | - Matthew Banks
- GI Services, University College London Hospital, London NW1 2BU, United Kingdom
| | - Rami Sweis
- GI Services, University College London Hospital, London NW1 2BU, United Kingdom
| | - Hannah Al-Yousuf
- GI Services, University College London Hospital, London NW1 2BU, United Kingdom
| | - Miriam Mitchison
- GI Services, University College London Hospital, London NW1 2BU, United Kingdom
| | - Durayd Alzoubaidi
- GI Services, University College London Hospital, London NW1 2BU, United Kingdom
| | | | - Laurence Lovat
- GI Services, University College London Hospital, London NW1 2BU, United Kingdom
- Division of Surgery and Science, University College London, London WC1E 6BT, United Kingdom
| | - Marco Novelli
- GI Services, University College London Hospital, London NW1 2BU, United Kingdom
| | - Marnix Jansen
- GI Services, University College London Hospital, London NW1 2BU, United Kingdom
- Division of Surgery and Science, University College London, London WC1E 6BT, United Kingdom
| | - Rehan Haidry
- GI Services, University College London Hospital, London NW1 2BU, United Kingdom
- Division of Surgery and Science, University College London, London WC1E 6BT, United Kingdom
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30
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Haisley KR, Hart CM, Kaempf AJ, Dash NR, Dolan JP, Hunter JG. Specific Tumor Characteristics Predict Upstaging in Early-Stage Esophageal Cancer. Ann Surg Oncol 2018; 26:514-522. [PMID: 30377918 DOI: 10.1245/s10434-018-6804-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2017] [Indexed: 01/29/2023]
Abstract
BACKGROUND Early-stage esophageal cancer (stages 0-1) has been shown to have relatively good outcomes after local endoscopic or surgical resection. For this reason, neoadjuvant chemoradiation usually is reserved for higher-stage disease. Some early tumors, however, are found after resection to be more advanced than predicted based on initial clinical staging, termed pathologic upstaging. Such tumors may have benefited from alternate treatment models had their true stage been known preoperatively. This study aimed to identify high-risk features in early esophageal cancers that might predict tumor upstaging and guide more individualized treatment algorithms. METHODS Through retrospective review of a single-institution foregut disease registry, we evaluated patients who underwent esophagectomy for high-grade dysplasia (Tis) or stage 1 esophageal cancer, searching for factors associated with pathologic upstaging. RESULTS The review included 110 patients (88% male, median age at diagnosis, 64.5 years) treated between January 2000 and June 2016. Upstaging occurred for 20.9% of the patients, and was more common for patients with angiolymphatic invasion (odds ratio [OR], 11.07; 95% confidence interval [CI], 2.96-41.44; P < 0.001) or signet-ring features (OR, 23.9; 95% CI, 2.6-216.8; P = 0.005). In the absence of other predictors, upstaging was associated with decreased overall survival (P = 0.006). CONCLUSIONS Approximately 20% of patients with early-stage esophageal cancer may be upstaged at resection. Angiolymphatic invasion and signet-ring features may predict tumors likely to be upstaged, resulting in decreased overall survival.
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Affiliation(s)
- Kelly R Haisley
- Division of Gastrointestinal and General Surgery, Department of Surgery, Oregon Health and Science University, Portland, OR, USA.
| | - Christopher M Hart
- Department of Surgery, University of California Los Angeles, Los Angeles, CA, USA
| | - Andy J Kaempf
- Knight Cancer Institute, Biostatistics Shared Resource, Oregon Health and Science University, Portland, OR, USA
| | - Nihar R Dash
- Department of GI Surgery and Liver Transplant, All India Institute of Medical Sciences, New Delhi, India
| | - James P Dolan
- Division of Gastrointestinal and General Surgery, Department of Surgery, Oregon Health and Science University, Portland, OR, USA
| | - John G Hunter
- Division of Gastrointestinal and General Surgery, Department of Surgery, Oregon Health and Science University, Portland, OR, USA
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31
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Feczko AF, Louie BE. Endoscopic Resection in the Esophagus. Thorac Surg Clin 2018; 28:481-497. [PMID: 30268294 DOI: 10.1016/j.thorsurg.2018.07.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
The article is a review of the principles behind endoscopic resection of esophageal dysplasia and early cancers. The techniques of endoscopic mucosal resection and endoscopic submucosal dissection are reviewed, and the supporting literature compared. Endoscopic resection is compared with esophagectomy for the management of these lesions and current areas of controversy with regard to T1b lesions and gastroesophageal reflux following resection are addressed.
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Affiliation(s)
- Andrew F Feczko
- Division of Thoracic Surgery, Swedish Cancer Institute, 1101 Madison Avenue, Seattle, WA 98104, USA
| | - Brian E Louie
- Division of Thoracic Surgery, Swedish Cancer Institute, 1101 Madison Avenue, Seattle, WA 98104, USA.
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32
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Mönig S, Chevallay M, Niclauss N, Zilli T, Fang W, Bansal A, Hoeppner J. Early esophageal cancer: the significance of surgery, endoscopy, and chemoradiation. Ann N Y Acad Sci 2018; 1434:115-123. [PMID: 30138532 DOI: 10.1111/nyas.13955] [Citation(s) in RCA: 50] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2018] [Revised: 07/18/2018] [Accepted: 07/26/2018] [Indexed: 12/22/2022]
Abstract
Early carcinomas of the esophagus are histologically classified as adenocarcinoma or squamous cell carcinoma and microscopically subdivided into mucosal and submucosal carcinomas depending on infiltration depth. The prevalence of lymph node metastasis in mucosal carcinoma remains low. However, lymph node metastases arise frequently from tumors with submucosal infiltration, with increasing prevalence in the deeper submucosal sublayers. According to current German guidelines, endoscopic resection is the recommended treatment in mucosal adenocarcinoma without histologic risk factors (lymphatic invasion 1, vascular invasion 1, >grade 2, R1-margin). In superficial submucosal infiltration without histologic risk factors, endoscopic resection can be considered. In squamous cell carcinoma, endoscopic resection is indicated up to middle layer mucosal carcinoma. Beyond these criteria, surgical resection should be considered. The gold standard is a subtotal transthoracic esophagectomy with two-field lymphadenectomy. Total esophagectomy is performed in cervical esophageal carcinoma and transhiatal extended gastrectomy in carcinoma of the cardia. Minimally invasive procedures show good oncologic results and reduce the morbidity of radical esophagectomy. Reduced morbidity might be an argument for surgical resection in borderline cases between endoscopic and surgical resection. In early squamous cell cancer, the combination of endoscopic resection and adjuvant chemoradiotherapy is a therapeutic option with promising results.
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Affiliation(s)
- Stefan Mönig
- Visceral Surgery Department, Geneva University Hospital, Geneva, Switzerland
| | - Mickael Chevallay
- Visceral Surgery Department, Geneva University Hospital, Geneva, Switzerland
| | - Nadja Niclauss
- Visceral Surgery Department, Geneva University Hospital, Geneva, Switzerland
| | - Thomas Zilli
- Department of Radiation Oncology, Geneva University Hospital, Geneva, Switzerland.,Faculty of Medicine, Geneva University, Geneva, Switzerland
| | - Wentao Fang
- Department of Thoracic Surgery, Shanghai Chest Hospital Clinical Center for Esophageal Diseases, Shanghai Jiaotong University, Shanghai, China
| | - Ajay Bansal
- Gastroenterology and Hepatology, University of Kansas Medical Center, Kansas City, Kansas.,Gastroenterology and Hepatology, Veterans Affairs Medical Center, Kansas City, Missouri
| | - Jens Hoeppner
- Department of General and Visceral Surgery, Faculty of Medicine, University of Freiburg Medical Center, Freiburg, Germany
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33
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Additional value of EUS in oesophageal cancer patients staged N0 on PET/CT: validation of a prognostic model. Surg Endosc 2018; 32:4973-4979. [PMID: 29869086 PMCID: PMC6208695 DOI: 10.1007/s00464-018-6259-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2018] [Accepted: 05/29/2018] [Indexed: 11/08/2022]
Abstract
Background Lymph node metastases are a major prognostic indicator in oesophageal cancer. Radiological staging largely influences treatment decisions and is becoming more reliant on PET and CT. However, the sensitivity of these modalities is suboptimal and is known to under-stage disease. The primary aim of this study was to validate a published prognostic model in oesophageal cancer patients staged N0 with PET/CT, which showed that EUS nodal status was an independent predictor of survival. The secondary aim was to assess the prognostic significance of pathological lymph node metastases in this cohort. Methods An independent validation cohort included 139 consecutive patients from a regional upper gastrointestinal cancer network staged N0 with PET/CT between 1st January 2013 and 31st June 2015. Replicating the original study, two Cox regression models were produced: one included EUS T-stage and EUS N-stage, and one included EUS T-stage and EUS N0 versus N+. The primary outcome of the prognostic model was overall survival (OS). Kaplan–Meier analysis assessed differences in OS between pathological node-negative (pN0) and node-positive (pN+) groups. A p value of < 0.05 was considered statistically significant. Results The mean OS of the validation cohort was 29.8 months (95% CI 27.1–35.2). EUS T-stage was significantly and independently associated with OS in both models (p = 0.011 and p = 0.012, respectively). EUS N-stage and EUS N0 versus N+ were not significantly associated with OS (p = 0.553 and p = 0.359, respectively). There was a significant difference in OS between pN0 and pN+ groups (χ2 13.315, df 1, p < 0.001). Conclusion Lymph node metastases have a significant detrimental effect on OS. This validation study did not replicate the results of the developed prognostic model but the continued benefit of EUS in patients staged N0 with PET/CT was demonstrated. EUS remains a valuable component of a multi-modality approach to oesophageal cancer staging.
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34
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Wang WL, Chiu SYH, Lee CT, Tseng CH, Chen CC, Han ML, Chung CS, Hsieh PH, Chang WL, Wu PH, Hsu WH, Yen HH, Wang HP, Chang CY. A training program of a new simplified classification of magnified narrow band imaging for superficial esophageal squamous cell carcinoma. J Gastroenterol Hepatol 2018; 33:1248-1255. [PMID: 29247549 DOI: 10.1111/jgh.14071] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2017] [Revised: 11/07/2017] [Accepted: 12/07/2017] [Indexed: 01/13/2023]
Abstract
BACKGROUND AND AIM Optimal staging of the invasion depth of superficial esophageal squamous cell carcinoma is vital before endoscopic treatment. A new simplified magnified narrow-band imaging (M-NBI) classification system based on vascular architecture has recently been developed by the Japan Esophageal Society; however, its validity remains uncertain. METHODS A total of 11 experienced and 11 inexperienced endoscopists were invited to join an endoscopic training program, which was composed of pretest, educational section, and post-test. The pretest and post-test sections included a set of endoscopic photos from 40 subjects with superficial esophageal squamous cell carcinoma with various invasion depths. Each subject appeared twice in the test, one with white-light imaging (WLI) only and the other with both WLI and M-NBI. The educational section included lectures and video demonstrations. RESULTS The accuracy of WLI alone and combined with M-NBI at baseline were 0.53, 0.57 and 0.43, 0.41 for the experienced and inexperienced endoscopists, respectively, which then improved to 0.57, 0.63 and 0.49, 0.52 after training. Inter-observer agreement (k-value) of WLI alone and combined WLI and M-NBI for the experienced and inexperienced endoscopists also improved from 0.61, 0.61, and 0.61, 0.53 to 0.68, 0.71, and 0.71, 0.59, respectively. Multivariate analysis revealed that the educational course but not experience in endoscopy, NBI, or magnification significantly improved the diagnostic accuracy. M-NBI had a significant additional benefit to WLI, with an improvement in accuracy from 36% to 56% for the cases with m3/sm1 cancers (P < 0.05). CONCLUSIONS A well-designed training program can improve the diagnostic accuracy in evaluating cancer invasion depth, with substantial agreement.
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Affiliation(s)
- Wen-Lun Wang
- Department of Internal Medicine, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan
| | - Sherry Yueh-Hsia Chiu
- Department of Health Care Management and Healthy Aging Research Center, Chang Gung University, Taoyuan, Taiwan.,Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Ching-Tai Lee
- Department of Internal Medicine, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan
| | - Cheng-Hao Tseng
- Department of Internal Medicine, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan
| | - Chien-Chuan Chen
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Ming-Lun Han
- Department of Internal Medicine, Min-Sheng General Hospital, Taoyan, Taiwan
| | - Chen-Shuan Chung
- Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan
| | - Ping-Hsin Hsieh
- Department of Gastroenterology, Chimei Medical Center, Tainan, Taiwan
| | - Wei-Lun Chang
- Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan
| | - Ping-Hsiu Wu
- Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
| | - Wen-Hung Hsu
- Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Hsu-Heng Yen
- Endoscopy Center, Changhua Christian Hospital, Changhua, Taiwan
| | - Hsiu-Po Wang
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Chi-Yang Chang
- Department of Internal Medicine, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan.,School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.,Department of Internal Medicine, Fu Jen Catholic University Hospital, New Taipei City, Taiwan
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35
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Haque W, Verma V, Bernicker E, Butler EB, Teh BS. Management of pathologic node-positive disease following initial surgery for clinical T1-2 N0 esophageal cancer: patterns of care and outcomes from the national cancer data base. Acta Oncol 2018; 57:782-789. [PMID: 29188742 DOI: 10.1080/0284186x.2017.1409435] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
PURPOSE Although clinical T1-2N0 esophageal cancer (EC) is often initially surgically resected (without neoadjuvant therapy), several studies have illustrated substantial rates of discovering pathologically node-positive disease. This study evaluated national practice patterns of adjuvant therapy for this population. METHODS The National Cancer Database (NCDB) was queried (2004-2013) for patients with cT1-2N0M0 EC that received up-front surgery (esophagectomy/local techniques) with subsequent discovery of nodal metastasis. Patients receiving any neoadjuvant therapy were excluded. Multivariable logistic regression determined factors predictive of receiving adjuvant therapy. Kaplan-Meier analysis evaluated overall survival (OS), and Cox proportional hazards modeling determined variables associated with OS. Propensity score matching assessed groups in a balanced manner while reducing indication biases. RESULTS Altogether, 715 patients met inclusion criteria; 114 (16%) underwent adjuvant chemotherapy, 183 (26%) chemoradiation, 16 (2%) radiotherapy alone, and 402 (56%) observation. Observation was more likely performed with advanced age (p = .002) and at nonacademic centers (p = .001). Median OS in the respective cohorts were 42.6, 35.1, 22.2, and 27.0 months. Both chemotherapy and chemoradiation were statistically similar (p = .462) but superior to observation (p < .05 for both). There was a survival benefit to any adjuvant treatment (median OS 38.5 vs. 27.0 months, p < .001), which persisted after propensity matching (median OS 35.1 vs. 24.3 months, p < .001). On multivariable analysis, any adjuvant treatment was independently associated with improved OS, along with treatment at an academic center (p < .05 for all). CONCLUSIONS In the largest study to date evaluating patterns of care for pN + disease following resection of cT1-2N0 EC, a strikingly high proportion of patients were observed. Adjuvant treatment, ideally chemotherapy or chemoradiation, independently correlated with higher survival, and should be considered in able patients. Treatment at academic facilities also associated with higher survival, which has implications for patient counseling.
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Affiliation(s)
- Waqar Haque
- Department of Radiation Oncology, Houston Methodist Hospital, Houston, TX, USA
| | - Vivek Verma
- Department of Radiation Oncology, University of Nebraska Medical Center, Omaha, NE, USA
| | - Eric Bernicker
- Department of Medical Oncology, Houston Methodist Hospital, Houston, TX, USA
| | - E. Brian Butler
- Department of Radiation Oncology, Houston Methodist Hospital, Houston, TX, USA
| | - Bin S. Teh
- Department of Radiation Oncology, Houston Methodist Hospital, Houston, TX, USA
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36
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Bourke MJ, Neuhaus H, Bergman JJ. Endoscopic Submucosal Dissection: Indications and Application in Western Endoscopy Practice. Gastroenterology 2018; 154:1887-1900.e5. [PMID: 29486200 DOI: 10.1053/j.gastro.2018.01.068] [Citation(s) in RCA: 73] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2017] [Revised: 01/11/2018] [Accepted: 01/11/2018] [Indexed: 12/11/2022]
Abstract
Endoscopic submucosal dissection was developed in Japan, early in this century, to provide a minimally invasive yet curative treatment for the large numbers of patients with early gastric cancer identified by the national screening program. Previously, the majority of these patients were treated surgically at substantial cost and with significant risk of short- and long-term morbidity. En-bloc excision of these early cancers, most with a limited risk of nodal metastasis, allowed complete staging of the tumor, stratification of the subsequent therapeutic approach, and potential cure. This transformative innovation changed the nature of endoscopic treatment for superficial mucosal neoplasia and, ultimately, for the first time allowed endoscopists to assert that the early cancer had been definitively cured. Subsequently, Western endoscopists have increasingly embraced the therapeutic possibilities offered by endoscopic submucosal dissection, but with some justifiable scientific caution. Here we provide an evidence-based critical appraisal of the role of endoscopic submucosal dissection in advanced endoscopic tissue resection.
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Affiliation(s)
- Michael J Bourke
- Department of Gastroenterology and Hepatology, Westmead Hospital, Sydney, New South Wales, Australia; Westmead Clinical School, The University of Sydney, Sydney, New South Wales, Australia.
| | - Horst Neuhaus
- Department of Internal Medicine, Evangelisches Krankenhaus Düsseldorf, Düsseldorf, Germany
| | - Jacques J Bergman
- Academic Medical Centre, Department of Gastroenterology and Hepatology, Amsterdam, Netherlands
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37
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Koyanagi K, Kato F, Kanamori J, Daiko H, Ozawa S, Tachimori Y. Clinical significance of esophageal invasion length for the prediction of mediastinal lymph node metastasis in Siewert type II adenocarcinoma: A retrospective single-institution study. Ann Gastroenterol Surg 2018; 2:187-196. [PMID: 29863189 PMCID: PMC5980392 DOI: 10.1002/ags3.12069] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2018] [Accepted: 03/12/2018] [Indexed: 01/13/2023] Open
Abstract
AIM This study investigated whether esophageal invasion length (EIL) of a tumor from the esophagogastric junction could be a possible indicator of mediastinal lymph node metastasis and survival in patients with Siewert type II adenocarcinoma. METHODS One hundred and sixty-eight patients with Siewert type II tumor who underwent surgery were enrolled. Metastatic stations and recurrent lymph node sites were classified into cervical, upper/middle/lower mediastinal, and abdominal zones. EIL was correlated with overall metastasis or recurrence in individual zones and with survival. RESULTS Siewert type II patients with an EIL of more than 25 mm (>25 mm EIL group) had a higher incidence of overall metastasis or recurrence in the upper and middle mediastinal zones than those with an EIL of less than or equal to 25 mm (≤25 mm EIL group) (P = .001 and P < .001). Disease-free and overall survival in the >25 mm EIL group were significantly lower than those of the ≤25 mm EIL group (P < .001). None of the Siewert type II patients with metastasis or recurrence in the upper and middle mediastinal zones survived for more than 5 years. Only an EIL of more than 25 mm was a significant preoperative predictor of overall metastasis or recurrence in the upper and middle mediastinal zones (odds ratio, 8.85; 95% CI, 2.31-33.3; P = .001). CONCLUSION A multimodal-therapeutic strategy should be investigated in Siewert type II patients once the tumor has invaded more than 25 mm to the esophageal wall.
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Affiliation(s)
- Kazuo Koyanagi
- Department of Esophageal SurgeryNational Cancer Center HospitalTokyoJapan
| | - Fumihiko Kato
- Department of Esophageal SurgeryNational Cancer Center HospitalTokyoJapan
| | - Jun Kanamori
- Department of Esophageal SurgeryNational Cancer Center HospitalTokyoJapan
| | - Hiroyuki Daiko
- Department of Esophageal SurgeryNational Cancer Center HospitalTokyoJapan
| | - Soji Ozawa
- Department of Gastroenterological SurgeryTokai University School of MedicineIseharaJapan
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Niclauss N, Chevallay M, Frossard JL, Mönig SP. [Surgical strategy for early stage carcinoma of the esophagus]. Chirurg 2018; 89:339-346. [PMID: 29392342 DOI: 10.1007/s00104-018-0589-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Early stage carcinomas of the esophagus are histologically differentiated into adenocarcinomas and squamous cell carcinomas and subdivided into mucosal (m1-3) and submucosal (sm1-3) carcinomas depending on the infiltration depth. While the prevalence of lymph node metastases in mucosal carcinomas is very low, the probability of lymph node metastases increases from submucosal infiltration with increasing depth. According to the current German S3 guidelines endoscopic resection is the recommended treatment strategy for mucosal adenocarcinoma without histological risk factors (lymphatic invasion [L1], venous invasion [V1], poorly differentiated [>G2], microscopic residual disease [R1] at the deep resection margin). For superficial submucosal infiltration (sm1) without histological risk factors endoscopic resection can also be carried out, whereby in this case the guidelines make a stronger recommendation for esophagectomy. For squamous cell carcinoma endoscopic resection is indicated for an infiltration depth up to middle layer mucosal carcinoma (m2) without histological risk factors. Outside of these criteria an esophageal resection should always be carried out. The surgical gold standard is a subtotal abdominothoracic esophagectomy with two-field lymphadenectomy. Alternative procedures are total esophagectomy in proximal esophageal carcinoma and transhiatal extended gastrectomy for carcinoma of the cardia. Limited proximal or distal esophageal resections can be performed in proximal or distal mucosal carcinoma without the possibility of endoscopic resection; however, partial resections are not superior in terms of functional results and are not oncologically equivalent due to limited lymphadenectomy. Minimally invasive procedures show good oncological results and reduce the morbidity of radical esophagectomy. Reduced morbidity might be an argument for surgical resection in borderline cases between endoscopic and surgical resection.
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Affiliation(s)
- N Niclauss
- Service de chirurgie viscérale, Hôpitaux Universitaires de Genève, Rue Gabrielle-Perret-Gentil 4, 1205, Genf, Schweiz
| | - M Chevallay
- Service de chirurgie viscérale, Hôpitaux Universitaires de Genève, Rue Gabrielle-Perret-Gentil 4, 1205, Genf, Schweiz
| | - J L Frossard
- Service de gastroentérologie et hépatologie, Hôpitaux Universitaires de Genève, Genf, Schweiz
| | - S P Mönig
- Service de chirurgie viscérale, Hôpitaux Universitaires de Genève, Rue Gabrielle-Perret-Gentil 4, 1205, Genf, Schweiz.
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39
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Luu C, Amaral M, Klapman J, Harris C, Almhanna K, Hoffe S, Frakes J, Pimiento JM, Fontaine JP. Endoscopic ultrasound staging for early esophageal cancer: Are we denying patients neoadjuvant chemo-radiation? World J Gastroenterol 2017; 23:8193-8199. [PMID: 29290655 PMCID: PMC5739925 DOI: 10.3748/wjg.v23.i46.8193] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2017] [Revised: 07/04/2017] [Accepted: 08/02/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the accuracy of endoscopic ultrasound (EUS) in early esophageal cancer (EC) performed in a high-volume tertiary cancer center.
METHODS A retrospective review of patients undergoing esophagectomy was performed and patients with cT1N0 and cT2N0 esophageal cancer by EUS were evaluated. Patient demographics, tumor characteristics, and treatment were reviewed. EUS staging was compared to surgical pathology to determine accuracy of EUS. Descriptive statistics was used to describe the cohort. Student’s t test and Fisher’s exact test or χ2 test was used to compare variables. Logistic regression analysis was used to determine if clinical variables such as tumor location and tumor histology were associated with EUS accuracy.
RESULTS Between 2000 and 2015, 139 patients with clinical stageIorIIA esophageal cancer undergoing esophagectomy were identified. There were 25 (18%) female and 114 (82%) male patients. The tumor location included the middle third of the esophagus in 11 (8%) and lower third and gastroesophageal junction in 128 (92%) patients. Ninety-three percent of patients had adenocarcinoma. Preoperative EUS matched the final surgical pathology in 73/139 patients for a concordance rate of 53%. Twenty-nine patients (21%) were under-staged by EUS; of those, 19 (14%) had unrecognized nodal disease. Positron emission tomography (PET) was used in addition to EUS for clinical staging in 62/139 patients. Occult nodal disease was only found in 4 of 62 patients (6%) in whom both EUS and PET were negative for nodal involvement.
CONCLUSION EUS is less accurate in early EC and endoscopic mucosal resection might be useful in certain settings. The addition of PET to EUS improves staging accuracy.
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Affiliation(s)
- Carrie Luu
- Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, United States
| | - Marisa Amaral
- Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, United States
| | - Jason Klapman
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, United States
| | - Cynthia Harris
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, United States
| | - Khaldoun Almhanna
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, United States
| | - Sarah Hoffe
- Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, United States
| | - Jessica Frakes
- Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, United States
| | - Jose M Pimiento
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, United States
| | - Jacques P Fontaine
- Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, United States
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40
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Chirurgische Strategie in der multimodalen Behandlung des Magen- und Ösophaguskarzinoms. Chirurg 2017; 88:1005-1009. [DOI: 10.1007/s00104-017-0545-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
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41
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Kadota T, Yano T, Fujita T, Daiko H, Fujii S. Submucosal Invasive Depth Predicts Lymph Node Metastasis and Poor Prognosis in Submucosal Invasive Esophageal Squamous Cell Carcinoma. Am J Clin Pathol 2017; 148:416-426. [PMID: 29069275 DOI: 10.1093/ajcp/aqx093] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023] Open
Abstract
OBJECTIVES Lymph node metastasis (LNM) in submucosal invasive esophageal squamous cell carcinoma (SM-ESCC) is a prognostic factor. The aim of this study was to identify a histopathologic predictor of LNM in SM-ESCC. METHODS In total, 108 patients who underwent an esophagectomy and lymph node dissection without preoperative therapy and who were pathologically diagnosed with SM-ESCC were enrolled in this study. Relationships between several clinicopathologic factors and LNM were examined. RESULTS A multivariate analysis revealed that a tumor size of 35 mm or more (P = .0025), submucosal invasive depth (SID) of 2,000 μm or more (P = .013), and lymphatic infiltration (P < .0001) were significant independent predictors of LNM. In addition, there were significant differences in recurrence-free survival curves between patients with SID less than 2,000 μm or not (P = .029) and tumor size less than 35 mm or not (P = .049). CONCLUSIONS This study suggests that SID may predict not only LNM but also poor prognosis.
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Affiliation(s)
| | | | - Takeo Fujita
- Esophageal Surgery, National Cancer Center Hospital East, Kashiwa, Japan
| | - Hiroyuki Daiko
- Esophageal Surgery, National Cancer Center Hospital East, Kashiwa, Japan
| | - Satoshi Fujii
- Division of Pathology, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Kashiwa, Japan
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Role of Adjuvant Treatment in Esophageal Cancer With Incidental Pathologic Node Positivity. Ann Thorac Surg 2017; 104:267-274. [DOI: 10.1016/j.athoracsur.2017.01.092] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2016] [Revised: 01/25/2017] [Accepted: 01/30/2017] [Indexed: 11/21/2022]
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Abstract
Endoscopic therapies have become the standard of care for most cases of Barrett's esophagus with high-grade dysplasia or intramucosal adenocarcinoma. Despite a rapid and dramatic evolution in treatment paradigms, esophagectomy continues to occupy a place in the therapeutic armamentarium for superficial esophageal neoplasia. The managing physician must remain cognizant of the limitations of endoscopic approaches and consider surgical resection when they are exceeded. Esophagectomy, performed at experienced centers for appropriately selected patients with early-stage disease can be undertaken with the expectation of cure as well as low mortality, acceptable morbidity, and good long-term quality of life.
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Affiliation(s)
- Thomas J Watson
- Division of Thoracic and Esophageal Surgery, Department of Surgery, MedStar Washington, Georgetown University School of Medicine, 3800 Reservoir Road Northwest, 4PHC, Washington, DC 20007, USA.
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Duan J, Deng T, Ying G, Zhang H, Zhou L, Bai M, Li H, Ba Y. Prognostic significance of the T2 substage in patients with esophageal squamous cell carcinoma. Dis Esophagus 2017; 30:1-7. [PMID: 28375473 DOI: 10.1093/dote/dow027] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2016] [Indexed: 12/11/2022]
Abstract
The invasion of the muscularis propria is defined as T2 stage in esophageal squamous cell carcinoma. Evidence is lacking regarding whether the T2 substage based on anatomy may serve as a prognostic indicator. This study aims to confirm the prognostic value of the T2 substage. The clinicopathological characteristics of 120 patients who had pathologically verified T2 tumors between 2006 and 2011 at the Tianjin Medical University Cancer Institute and Hospital were retrospectively studied. Based on the invasion depth, tumors that had penetrated the circular muscle layer were defined as T2a, while T2b disease referred to those that had invaded the longitudinal muscle layer. Factors potentially related to survival were analyzed with univariate and multivariate analyses. The logistic regression model was used to examine the factors associated with lymph node metastasis. To verify the prognostic value of the T2 substage further, patients with T1b and T3 stage disease during the same period were selected for comparisons. The univariate and multivariate analyses demonstrated that the T2 substage and N stage were independent prognostic factors. The T2 substage was highly relevant to lymph node metastasis in the logistic regression model (P = 0.044). When T1b and T3 was considered, the survival of T2a patients was closer to that of T1b patients, while the survival of T2b patients was closer to that of T3 disease (P = 0.000). The T2 substage was an independent prognostic factor. Patients with T2a tumors displayed a favorable survival, while the prognosis of T2b patients was closer to that of T3 patients.
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Endoscopic mucosal resection versus esophagectomy for intramucosal adenocarcinoma in the setting of barrett's esophagus. Surg Endosc 2017; 31:4211-4216. [PMID: 28342132 DOI: 10.1007/s00464-017-5479-z] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2016] [Accepted: 02/16/2017] [Indexed: 12/20/2022]
Abstract
BACKGROUND Esophagectomy has been the standard of care for patients with intramucosal adenocarcinoma (IMC) in the setting of Barrett's esophagus. It is, however, associated with significant post-operative morbidity and mortality. Endoscopic mucosal resection (EMR) offers a minimally invasive approach with lesser morbidity. This study investigates the transition from esophagectomy to EMR for IMC with respect to eradication rates, post-operative morbidity, and long-term survival. METHODS Patients diagnosed with IMC from 2005 to 2013 were identified retrospectively. Beginning in 2009, preferred initial therapy for IMC transitioned from esophagectomy to EMR. Esophagectomy was performed either through a transthoracic or transhiatal technique. EMR was repeated until resolution of IMC on pathology or progression of disease. Continuous data are expressed as mean (SD) and analyzed using Student's t test. Categorical data are presented as number (%) and analyzed using Fisher's exact test. RESULTS We identified 23 patients; 12 patients underwent esophagectomy and 11 patients underwent EMR as initial therapy. Patients were similar with respects to age, gender, and comorbidity index. Most tumors arose from short segment (vs long segment) Barrett's (esophagectomy: 9 (75%) vs. EMR: 10 (91%), p = 0.59) and one patient in each group had superficial invasion into the submucosa (T1sm1), the remainder having mucosal disease. Esophagectomy was associated with 7 (58%) minor complications and 2 (17%) major complications (respiratory failure, anastomotic leak), whereas there were no complications related to EMR (p < 0.01). EMR successfully eradicated IMC in 10 patients (91%) with one progressing to esophagectomy. Patients required 2 (1) endoscopies to achieve eradication. There was one mortality in each group on long-term follow-up (log-rank test, p = 0.62). CONCLUSIONS EMR was successful in eradicating IMC in 10/11 patients with similar long-term recurrence and mortality to esophagectomy patients. Patients with IMC may benefit from EMR as initial therapy by obviating the need for a complex and morbid operation.
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Yamashita H, Seto Y, Sano T, Makuuchi H, Ando N, Sasako M. Results of a nation-wide retrospective study of lymphadenectomy for esophagogastric junction carcinoma. Gastric Cancer 2017; 20:69-83. [PMID: 27796514 DOI: 10.1007/s10120-016-0663-8] [Citation(s) in RCA: 147] [Impact Index Per Article: 18.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2016] [Accepted: 10/15/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND Esophagogastric junction (EGJ) carcinoma has attracted considerable attention because of the marked increase in its incidence globally. However, the optimal extent of esophagogastric resection for this tumor entity remains highly controversial. METHODS This was a questionnaire-based national retrospective study undertaken in an attempt to define the optimal extent of lymph node dissection for EGJ cancer. Data from patients with EGJ carcinoma, less than 40 mm in diameter, who underwent R0 resection between January 2001 and December 2010 were reviewed. RESULTS Clinical records of 2807 patients without preoperative therapy were included in the analysis. There are distinct disparities in terms of the nodal dissection rate according to histology and the predominant tumor location. Nodal metastases frequently involved the abdominal nodes, especially those at the right and left cardia, lesser curvature and along the left gastric artery. Nodes along the distal portion of the stomach were much less often metastatic, and their dissection seemed unlikely to be beneficial. Lower mediastinal node dissection might contribute to improving survival for patients with esophagus-predominant EGJ cancer. However, due to low dissection rates for nodes of the middle and upper mediastinum, no conclusive result was obtained regarding the optimal extent of nodal dissection in this region. CONCLUSIONS Complete nodal clearance along the distal portion of the stomach offers marginal survival benefits for patients with EGJ cancers less than 4 cm in diameter. The optimal extent of esophageal resection and the benefits of mediastinal node dissection remain issues to be addressed in managing patients with esophagus-predominant EGJ cancers.
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Affiliation(s)
- Hiroharu Yamashita
- Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
| | - Yasuyuki Seto
- Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Takeshi Sano
- Department of Gastroenterological Surgery, Cancer Institute Hospital, 3-8-31, Ariake, Koto-ku, Tokyo, 135-8550, Japan
| | - Hiroyasu Makuuchi
- Department of Surgery, Tokai University School of Medicine, Isehara, Kanagawa, 259-1193, Japan
| | - Nobutoshi Ando
- International Goodwill Hospital, Yokohama, Kanagawa, 245-0006, Japan
| | - Mitsuru Sasako
- Department of Multidisciplinary Surgical Oncology, Hyogo College of Medicine, 1-1, Mukogawacho, Nishinomiya, Hyogo, 663-8501, Japan
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Manner H, Wetzka J, May A, Pauthner M, Pech O, Fisseler-Eckhoff A, Stolte M, Vieth M, Lorenz D, Ell C. Early-stage adenocarcinoma of the esophagus with mid to deep submucosal invasion (pT1b sm2-3): the frequency of lymph-node metastasis depends on macroscopic and histological risk patterns. Dis Esophagus 2017; 30:1-11. [PMID: 26952572 DOI: 10.1111/dote.12462] [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] [Indexed: 02/06/2023]
Abstract
The rate of lymph-node (LN) metastasis in early adenocarcinoma (EAC) of the esophagus with mid to deep submucosal invasion (pT1b sm2/3) has not yet been precisely defined. The aim of the this study was to evaluate the rate of LN metastasis in pT1b sm2/3 EAC depending on macroscopic and histological risk patterns to find out whether there may also be options for endoscopic therapy as in cancers limited to the mucosa and the upper third of the submucosa. A total of 1.718 pt with suspicion of EAC were referred for endoscopic treatment (ET) to the Dept. of Internal Medicine II at HSK Wiesbaden 1996-2010. In 230/1.718 pt, the suspicion (endoscopic ultrasound, EUS) or definitive diagnosis of pT1b EAC (ER/surgery) was made. Of these, 38 pt had sm2 lesions, and 69 sm3. Rate of LN metastasis was analyzed depending on risk patterns: histologically low-risk (hisLR): G1-2, L0, V0; histologically high-risk (hisHR): ≥1 criterion not fulfilled; macroscopically low-risk (macLR): gross tumor type I-II, tumor size ≤2 cm; macroscopically high-risk (macHR): ≥1 criterion not fulfilled; combined low-risk (combLR): hisLR+macLR; combined high-risk (combHR): at least 1 risk factor. LN rate was only evaluated in pt who had proven maximum invasion depth of sm2/sm3, and who in case of ET had a follow-up (FU) by EUS of at least 24 months. 23/38 pt with pT1b sm2 lesions and 39/69 pt with sm3 lesions fulfilled our inclusion criteria. In the pT1b sm2 group, rate of LN metastasis in the hisLR, hisHR, combLR, and combHR groups were 8.3% (1/12), 36.3% (4/11), 0% (0/5), and 27.8% (5/18). In the pT1b sm3 group, rate of LN metastasis in the hisLR, hisHR, combLR and combHR groups were 28.6% (2/7), 37.5% (12/32), 25% (1/4), and 37.1% (13/35). 30-day mortality of surgery was 1.7% (1/58 pt). In EAC with pT1b sm2/3 invasion, the frequency of LN metastasis depends on macroscopic and histological risk patterns. Surgery remains the standard treatment, because the rate of LN metastasis appears to be higher than the mortality risk of surgery. Whether a highly selected group of pT1b sm2 patients with a favourable risk pattern may be candidates for endoscopic therapy cannot be decided until the results of larger case volumes are available.
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Affiliation(s)
- H Manner
- Department of Internal Medicine II, HSK Hospital, Teaching Hospital of the University Medicine of Mainz, Wiesbaden, Germany
| | - J Wetzka
- Department of Internal Medicine II/IV, Sana Klinikum Offenbach, Teaching Hospital of the University Medicine of Frankfurt, Germany
| | - A May
- Department of Internal Medicine II/IV, Sana Klinikum Offenbach, Teaching Hospital of the University Medicine of Frankfurt, Germany
| | - M Pauthner
- Department of General and Visceral Surgery, Sana Klinikum Offenbach, Teaching Hospital of the University Medicine of Frankfurt, Germany
| | - O Pech
- Department of Gastroenterology and Interventional Endoscopy, St. John of God Hospital, Regensburg, Germany
| | | | - M Stolte
- Institute of Pathology, Kulmbach Hospital, Germany
| | - M Vieth
- Institute of Pathology, Bayreuth Hospital, Germany
| | - D Lorenz
- Department of General and Visceral Surgery, Sana Klinikum Offenbach, Teaching Hospital of the University Medicine of Frankfurt, Germany
| | - C Ell
- Department of Internal Medicine II/IV, Sana Klinikum Offenbach, Teaching Hospital of the University Medicine of Frankfurt, Germany
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Old OJ, Isabelle M, Barr H. Staging Early Esophageal Cancer. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2017; 908:161-81. [PMID: 27573772 DOI: 10.1007/978-3-319-41388-4_9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Staging esophageal cancer provides a standardized measure of the extent of disease that can be used to inform decisions about therapy and guide prognosis. For esophageal cancer, the treatment pathways vary greatly depending on stage of disease, and accurate staging is therefore crucial in ensuring the optimal therapy for each patient. For early esophageal cancer (T1 lesions), endoscopic resection can be curative and simultaneously gives accurate staging of depth of invasion. For tumors invading the submucosa or more advanced disease, comprehensive investigation is required to accurately stage the tumor and assess suitability for curative resection. A combined imaging approach of computed tomography (CT), positron emission tomography (PET), and endoscopic ultrasound (EUS) offers complementary diagnostic information and gives the greatest chance of accurate staging. Staging laparoscopy can identify peritoneal disease and small superficial liver lesions that could be missed on CT or PET, and alters management in up to 20 % of patients. Optical diagnostic techniques offer the prospect of further extending the possibilities of endoscopic staging in real time. Optical coherence tomography can image superficial lesions and could provide information on depth of invasion for these lesions. Real-time lymph node analysis using optical diagnostics such as Raman spectroscopy could be used to support immediate endoscopic therapy without waiting for results of cytology or further investigations.
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Affiliation(s)
- O J Old
- Upper GI Surgery Department, Gloucestershire Royal Hospital, Gloucester, UK. .,Biophotonics Research Unit, Gloucestershire Royal Hospital, Gloucester, UK.
| | - M Isabelle
- Biophotonics Research Unit, Gloucestershire Royal Hospital, Gloucester, UK
| | - H Barr
- Upper GI Surgery Department, Gloucestershire Royal Hospital, Gloucester, UK
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Rice TW, Ishwaran H, Hofstetter WL, Schipper PH, Kesler KA, Law S, Lerut EMR, Denlinger CE, Salo JA, Scott WJ, Watson TJ, Allen MS, Chen LQ, Rusch VW, Cerfolio RJ, Luketich JD, Duranceau A, Darling GE, Pera M, Apperson-Hansen C, Blackstone EH. Esophageal Cancer: Associations With (pN+) Lymph Node Metastases. Ann Surg 2017; 265:122-129. [PMID: 28009736 PMCID: PMC5405457 DOI: 10.1097/sla.0000000000001594] [Citation(s) in RCA: 84] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
OBJECTIVES To identify the associations of lymph node metastases (pN+), number of positive nodes, and pN subclassification with cancer, treatment, patient, geographic, and institutional variables, and to recommend extent of lymphadenectomy needed to accurately detect pN+ for esophageal cancer. SUMMARY BACKGROUND DATA Limited data and traditional analytic techniques have precluded identifying intricate associations of pN+ with other cancer, treatment, and patient characteristics. METHODS Data on 5806 esophagectomy patients from the Worldwide Esophageal Cancer Collaboration were analyzed by Random Forest machine learning techniques. RESULTS pN+, number of positive nodes, and pN subclassification were associated with increasing depth of cancer invasion (pT), increasing cancer length, decreasing cancer differentiation (G), and more regional lymph nodes resected. Lymphadenectomy necessary to accurately detect pN+ is 60 for shorter, well-differentiated cancers (<2.5 cm) and 20 for longer, poorly differentiated ones. CONCLUSIONS In esophageal cancer, pN+, increasing number of positive nodes, and increasing pN classification are associated with deeper invading, longer, and poorly differentiated cancers. Consequently, if the goal of lymphadenectomy is to accurately define pN+ status of such cancers, few nodes need to be removed. Conversely, superficial, shorter, and well-differentiated cancers require a more extensive lymphadenectomy to accurately define pN+ status.
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Affiliation(s)
- Thomas W Rice
- *Cleveland Clinic, Cleveland, OH †University of Miami, Miami, FL ‡University of Texas, MD Anderson Cancer Center, Houston, TX §Oregon Health and Science Center, Portland, OR ¶Indiana University, Indianapolis, IN ||Queen Mary Hospital, The University of Hong Kong, People's Republic of China **University Hospital Leuven, Leuven, Belgium ††Medical University of South Carolina, Charleston, SC ‡‡Helsinki University Hospital, Helsinki, Finland §§Fox Chase Cancer Center, Philadelphia, PA ¶¶University of Rochester, Rochester, New York, NY ||||Mayo Clinic, Rochester, MN ***West China Hospital of Sichuan University, Chengdu, Sichuan, People's Republic of China †††Memorial Sloan-Kettering Cancer Center, New York, NY ‡‡‡University of Alabama at Birmingham, Birmingham, AL §§§University of Pittsburgh School of Medicine, Pittsburgh, PA ¶¶¶University of Montreal, Montreal, Canada ||||||Toronto General Hospital, Toronto, Canada ****Hospital Universitario del Mar, Institut Hospital del Mar d'Investigacions Mèdiques, Universitat Autònoma de Barcelona, Barcelona, Spain
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Schölvinck D, Künzli H, Meijer S, Seldenrijk K, van Berge Henegouwen M, Bergman J, Weusten B. Management of patients with T1b esophageal adenocarcinoma: a retrospective cohort study on patient management and risk of metastatic disease. Surg Endosc 2016; 30:4102-13. [PMID: 27357927 DOI: 10.1007/s00464-016-5071-y] [Citation(s) in RCA: 62] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2016] [Accepted: 06/21/2016] [Indexed: 12/23/2022]
Abstract
BACKGROUND Esophagectomy for submucosal (T1b) esophageal adenocarcinoma (EAC) is performed in order to optimize patient outcomes given the risk of concurrent lymph node metastases (LNM). However, not seldom, comorbidity precludes these patients from surgery. Therefore, the aim of our study was to assess the course of follow-up after treatment in submucosal EAC patients undergoing surgery versus conservative therapy and to evaluate the incidence of metastatic disease. METHODS Between 2001 and 2012, all patients undergoing diagnostic endoscopic resection for EAC in two centers were reviewed. Only patients with histopathologically proven submucosal tumor invasion were included. Submucosal EACs were divided into tumors that were removed radically (R0) and irradically (R1). Subsequently, in the R0 group, EACs were classified as either low risk (LR; submucosal invasion <500 nm, G1-G2, no LVI) or high risk (HR; deep submucosal invasion >500 nm, G3-G4 and/or LVI). Metastatic disease was defined as LNM in surgical resection specimen and/or evidence of malignant disease during follow-up (FU). RESULTS Sixty-nine patients with a submucosal EAC were included [23 R1-resections and 46 R0-resection (14 R0-LR and 32 R0-HR)]. Twenty-six patients underwent surgical treatment (1 R0-LR, 12 R0-HR and 13 R1). None of the 14 R0-LR patients developed metastatic disease after a median FU of 60 months. In the R0-HR group and R1 group, metastatic disease was diagnosed in 16 and 30 % of patients, respectively. Surgical patients tended to have a better overall survival than non-surgical patients (p = 0.09). Tumor-related deaths, however, were 12 % in both groups. CONCLUSIONS In LR submucosal EAC, the risk of metastatic disease appears to be very low. In deep submucosal EAC (either R0- or R1-resection), the rate of metastatic disease is lower than reported in earlier surgical series. Given the reasonable disease-free survival and high background mortality, conservative management of these patients seems to be a valid alternative for surgery in selected cases.
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Affiliation(s)
- Dirk Schölvinck
- Department of Gastroenterology and Hepatology, St. Antonius Hospital, Nieuwegein, Nieuwegein, The Netherlands.,Department of Gastroenterology and Hepatology, Academic Medical Center Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands
| | - Hannah Künzli
- Department of Gastroenterology and Hepatology, St. Antonius Hospital, Nieuwegein, Nieuwegein, The Netherlands.,Department of Gastroenterology and Hepatology, Academic Medical Center Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands
| | - Sybren Meijer
- Department of Pathology, Academic Medical Center Amsterdam, Amsterdam, The Netherlands
| | - Kees Seldenrijk
- Department of Pathology, St. Antonius Hospital, Nieuwegein, Nieuwegein, The Netherlands
| | | | - Jacques Bergman
- Department of Gastroenterology and Hepatology, Academic Medical Center Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands
| | - Bas Weusten
- Department of Gastroenterology and Hepatology, St. Antonius Hospital, Nieuwegein, Nieuwegein, The Netherlands. .,Department of Gastroenterology and Hepatology, Academic Medical Center Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
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